Trial Outcomes & Findings for ATX Study:A Study of Avastin (Bevacizumab), Tarceva (Erlotinib) and Xeloda (Capecitabine) in Patients With Locally Advanced and/or Metastatic Pancreatic Cancer (NCT NCT00925769)
NCT ID: NCT00925769
Last Updated: 2015-08-07
Results Overview
MTD for each of the medications was defined as the lowest dose studied which resulted in dose limiting toxicity (DLT) in at least 33 percent (%) of participants of the same quality category. DLT was defined as any greater than or equal to (\>=) Grade (G) 3 or G4 toxicity; \>= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting \>= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for \>= 7 days, and/or cancellation of one or more BEV infusion(s) due to adverse events (AEs).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
Up to Week 6 (Cycle 1-3)
Results posted on
2015-08-07
Participant Flow
Thirty two (32) participants were included however, 2 participants discontinued before reaching the end of the evaluation period of 3 cycles of the complete study regimen (of all 3 drugs) at the recommended dose due to progressive disease.
Participant milestones
| Measure |
ERL+BEV+CAP Dose Level-1
Participants were administered oral 100 milligrams (mg) of erlotinib (ERL) tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 milligrams per kilogram (mg/kg) of bevacizumab (BEV) intravenous (IV) infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 milligrams per square meter (mg/m\^2) of capecitabine (CAP) tablet twice daily (BID) within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
6
|
3
|
3
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
6
|
6
|
6
|
3
|
3
|
Reasons for withdrawal
| Measure |
ERL+BEV+CAP Dose Level-1
Participants were administered oral 100 milligrams (mg) of erlotinib (ERL) tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 milligrams per kilogram (mg/kg) of bevacizumab (BEV) intravenous (IV) infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 milligrams per square meter (mg/m\^2) of capecitabine (CAP) tablet twice daily (BID) within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Overall Study
Major toxicity
|
1
|
0
|
1
|
1
|
0
|
0
|
|
Overall Study
Disease progression
|
4
|
5
|
3
|
4
|
2
|
3
|
|
Overall Study
Death
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Missing documentation
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
End of study visit not done
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Participant is unable to swallow drug
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
ATX Study:A Study of Avastin (Bevacizumab), Tarceva (Erlotinib) and Xeloda (Capecitabine) in Patients With Locally Advanced and/or Metastatic Pancreatic Cancer
Baseline characteristics by cohort
| Measure |
Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
n=30 Participants
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (Dose levels \[DL\]-1, 2, 3, 4, 5 and 6) were administered either oral 100 mg or 150 mg of erlotinib tablet daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|
|
Age, Continuous
|
63.9 years
STANDARD_DEVIATION 8.4 • n=99 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Up to Week 6 (Cycle 1-3)Population: Per-protocol population.
MTD for each of the medications was defined as the lowest dose studied which resulted in dose limiting toxicity (DLT) in at least 33 percent (%) of participants of the same quality category. DLT was defined as any greater than or equal to (\>=) Grade (G) 3 or G4 toxicity; \>= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting \>= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for \>= 7 days, and/or cancellation of one or more BEV infusion(s) due to adverse events (AEs).
Outcome measures
| Measure |
Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
n=30 Participants
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Part 1: Maximum Tolerated Dose (MTD) of Capecitabine
|
900 mg/m^2 BID
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to Week 6 (Cycle 1-3)Population: Per-protocol population.
MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as \>= G3 or G4 toxicity; \>= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting \>= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for \>= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs.
Outcome measures
| Measure |
Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
n=30 Participants
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Part 1: MTD of Erlotinib
|
NA mg/day
DLTs were not observed for the maximum planned dose of erlotinib (150 mg/day) in the study; therefore, MTD was not defined for erlotinib.
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to Week 6 (Cycle 1-3)Population: Per-protocol population.
MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as \>= G3 or G4 toxicity; \>= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting \>= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for \>= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs.
Outcome measures
| Measure |
Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
n=30 Participants
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Part 1: MTD of Bevacizumab
|
NA mg/kg once every 2 weeks (Q2W)
DLTs were not observed for the maximum planned dose of bevacizumab (10 mg/kg once Q2W) in the study; therefore, MTD was not defined for capecitabine.
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to Week 6 (Cycle 1-3)Population: Per-protocol population.
Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in dose limiting toxicity (DLT) in at least 33% of participants of the same quality category. DLT was defined as \>= G3 or G4 toxicity; \>= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting \>= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for \>= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2.
Outcome measures
| Measure |
Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
n=30 Participants
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Part 1: Preliminary Recommended Dose (PRD) of Capecitabine for Part 2
|
800 mg/m^2 BID
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to Week 6 (Cycle 1-3)Population: Per-protocol population.
Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as \>= G3 or G4 toxicity; \>= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting \>= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for \>= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2.
Outcome measures
| Measure |
Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
n=30 Participants
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Part 1: PRD of Erlotinib for Part 2
|
150 mg/day
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to Week 6 (Cycle 1-3)Population: Per-protocol population.
Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as \>= G3 or G4 toxicity; \>= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting \>= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for \>= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2.
Outcome measures
| Measure |
Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
n=30 Participants
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Part 1: PRD of Bevacizumab for Part 2
|
10 mg/kg Q2W
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)Population: Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively.
Outcome measures
| Measure |
Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
n=6 Participants
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
n=6 Participants
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
n=6 Participants
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
n=6 Participants
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
n=3 Participants
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
n=3 Participants
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Part 1: Maximum Serum Concentration (Cmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR] and 5'-Deoxy-5-Fluorouridine [5'-DFUR])
Erlotinib (n=6,6,6,6,3,3)
|
1.50 micrograms per milliliter (µg/mL)
Standard Deviation 1.21
|
0.95 micrograms per milliliter (µg/mL)
Standard Deviation 0.58
|
0.68 micrograms per milliliter (µg/mL)
Standard Deviation 0.34
|
0.93 micrograms per milliliter (µg/mL)
Standard Deviation 0.63
|
0.58 micrograms per milliliter (µg/mL)
Standard Deviation 0.15
|
1.69 micrograms per milliliter (µg/mL)
Standard Deviation 0.67
|
|
Part 1: Maximum Serum Concentration (Cmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR] and 5'-Deoxy-5-Fluorouridine [5'-DFUR])
OSI-420 (n=6,6,6,6,3,3)
|
0.09 micrograms per milliliter (µg/mL)
Standard Deviation 0.07
|
0.05 micrograms per milliliter (µg/mL)
Standard Deviation 0.03
|
0.04 micrograms per milliliter (µg/mL)
Standard Deviation 0.02
|
0.06 micrograms per milliliter (µg/mL)
Standard Deviation 0.04
|
0.03 micrograms per milliliter (µg/mL)
Standard Deviation 0.01
|
0.10 micrograms per milliliter (µg/mL)
Standard Deviation 0.02
|
|
Part 1: Maximum Serum Concentration (Cmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR] and 5'-Deoxy-5-Fluorouridine [5'-DFUR])
Capecitabine (n=6,6,6,6,3,3)
|
1.69 micrograms per milliliter (µg/mL)
Standard Deviation 1.22
|
1.13 micrograms per milliliter (µg/mL)
Standard Deviation 0.61
|
4.89 micrograms per milliliter (µg/mL)
Standard Deviation 4.23
|
5.48 micrograms per milliliter (µg/mL)
Standard Deviation 4.51
|
9.47 micrograms per milliliter (µg/mL)
Standard Deviation 5.19
|
9.9 micrograms per milliliter (µg/mL)
Standard Deviation 5.01
|
|
Part 1: Maximum Serum Concentration (Cmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR] and 5'-Deoxy-5-Fluorouridine [5'-DFUR])
5'-DFCR (n=5,5,6,6,3,3)
|
3.5 micrograms per milliliter (µg/mL)
Standard Deviation 3.02
|
4.28 micrograms per milliliter (µg/mL)
Standard Deviation 1.61
|
11.46 micrograms per milliliter (µg/mL)
Standard Deviation 5.32
|
6.26 micrograms per milliliter (µg/mL)
Standard Deviation 2.05
|
5.44 micrograms per milliliter (µg/mL)
Standard Deviation 2.43
|
4.15 micrograms per milliliter (µg/mL)
Standard Deviation 1.24
|
|
Part 1: Maximum Serum Concentration (Cmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR] and 5'-Deoxy-5-Fluorouridine [5'-DFUR])
5'-DFUR (n=4,5,6,6,3,3)
|
7.9 micrograms per milliliter (µg/mL)
Standard Deviation 4.41
|
7.3 micrograms per milliliter (µg/mL)
Standard Deviation 2.74
|
6.17 micrograms per milliliter (µg/mL)
Standard Deviation 2.63
|
7.24 micrograms per milliliter (µg/mL)
Standard Deviation 3.35
|
3.28 micrograms per milliliter (µg/mL)
Standard Deviation 0.72
|
5.1 micrograms per milliliter (µg/mL)
Standard Deviation 2.35
|
SECONDARY outcome
Timeframe: CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)Population: Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively.
Outcome measures
| Measure |
Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
n=6 Participants
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
n=6 Participants
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
n=6 Participants
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
n=6 Participants
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
n=3 Participants
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
n=3 Participants
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Part 1: Time to Reach Cmax (Tmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
Erlotinib (n=6,6,6,6,3,3)
|
2.50 hours (h)
Interval 1.0 to 8.0
|
2.00 hours (h)
Interval 2.0 to 8.0
|
2.00 hours (h)
Interval 1.0 to 6.0
|
3.00 hours (h)
Interval 2.0 to 8.0
|
5.00 hours (h)
Interval 4.0 to 6.0
|
2.00 hours (h)
Interval 2.0 to 3.0
|
|
Part 1: Time to Reach Cmax (Tmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
OSI-420 (n=6,6,6,6,3,3)
|
3.00 hours (h)
Interval 1.0 to 8.0
|
2.00 hours (h)
Interval 2.0 to 24.0
|
2.00 hours (h)
Interval 1.0 to 8.0
|
7.00 hours (h)
Interval 2.0 to 24.0
|
6.00 hours (h)
Interval 6.0 to 6.0
|
4.00 hours (h)
Interval 2.0 to 4.0
|
|
Part 1: Time to Reach Cmax (Tmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
Capecitabine (n=6,6,6,6,3,3)
|
0.5 hours (h)
Interval 0.5 to 5.0
|
1 hours (h)
Interval 0.5 to 3.0
|
1.5 hours (h)
Interval 0.5 to 3.0
|
0.75 hours (h)
Interval 0.5 to 2.0
|
1 hours (h)
Interval 0.5 to 2.0
|
0.5 hours (h)
Interval 0.5 to 1.0
|
|
Part 1: Time to Reach Cmax (Tmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
5'-DFCR (n=5,5,6,6,3,3)
|
0.5 hours (h)
Interval 0.5 to 2.5
|
1 hours (h)
Interval 1.0 to 1.5
|
1.5 hours (h)
Interval 0.5 to 2.5
|
1 hours (h)
Interval 0.5 to 2.0
|
1 hours (h)
Interval 0.5 to 2.5
|
1.5 hours (h)
Interval 0.5 to 2.5
|
|
Part 1: Time to Reach Cmax (Tmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
5'-DFUR (n=4,5,6,6,3,3)
|
1 hours (h)
Interval 1.0 to 2.5
|
1.5 hours (h)
Interval 1.0 to 2.0
|
1.5 hours (h)
Interval 0.5 to 2.5
|
1.5 hours (h)
Interval 0.5 to 2.0
|
1 hours (h)
Interval 0.5 to 2.5
|
1.5 hours (h)
Interval 1.0 to 2.0
|
SECONDARY outcome
Timeframe: CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)Population: Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively.
Outcome measures
| Measure |
Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
n=6 Participants
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
n=6 Participants
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
n=6 Participants
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
n=6 Participants
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
n=3 Participants
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
n=3 Participants
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Part 1: Last Quantifiable Drug Concentration (Clast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
5'-DFCR (n=5,5,6,6,3,3)
|
0.23 µg/mL
Standard Deviation 0.23
|
0.08 µg/mL
Standard Deviation 0.04
|
0.64 µg/mL
Standard Deviation 0.6
|
0.75 µg/mL
Standard Deviation 0.89
|
0.99 µg/mL
Standard Deviation 1.22
|
0.3 µg/mL
Standard Deviation 0.1
|
|
Part 1: Last Quantifiable Drug Concentration (Clast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
Erlotinib (n=6,6,6,6,3,3)
|
0.37 µg/mL
Standard Deviation 0.36
|
0.31 µg/mL
Standard Deviation 0.19
|
0.23 µg/mL
Standard Deviation 0.11
|
0.39 µg/mL
Standard Deviation 0.39
|
0.23 µg/mL
Standard Deviation 0.02
|
0.52 µg/mL
Standard Deviation 0.19
|
|
Part 1: Last Quantifiable Drug Concentration (Clast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
OSI-420 (n=6,6,6,6,3,3)
|
0.04 µg/mL
Standard Deviation 0.06
|
0.02 µg/mL
Standard Deviation 0.01
|
0.01 µg/mL
Standard Deviation 0.01
|
0.04 µg/mL
Standard Deviation 0.04
|
0.01 µg/mL
Standard Deviation 0.00
|
0.04 µg/mL
Standard Deviation 0.01
|
|
Part 1: Last Quantifiable Drug Concentration (Clast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
Capecitabine (n=6,6,6,6,3,3)
|
0.05 µg/mL
Standard Deviation 0.06
|
0.2 µg/mL
Standard Deviation 0.2
|
0.17 µg/mL
Standard Deviation 0.15
|
0.06 µg/mL
Standard Deviation 0.03
|
0.29 µg/mL
Standard Deviation 0.26
|
0.17 µg/mL
Standard Deviation 0.1
|
|
Part 1: Last Quantifiable Drug Concentration (Clast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
5'-DFUR (n=4,5,6,6,3,3)
|
2.54 µg/mL
Standard Deviation 0.14
|
1.03 µg/mL
Standard Deviation 1.05
|
0.77 µg/mL
Standard Deviation 0.92
|
0.58 µg/mL
Standard Deviation 0.49
|
0.14 µg/mL
Standard Deviation 0.08
|
0.14 µg/mL
Standard Deviation 0.05
|
SECONDARY outcome
Timeframe: CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)Population: Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively.
Outcome measures
| Measure |
Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
n=6 Participants
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m\^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
n=6 Participants
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
n=6 Participants
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
n=6 Participants
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
n=3 Participants
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
n=3 Participants
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
Erlotinib (n=6,6,6,6,3,3)
|
15.81 h*µg/mL
Standard Deviation 12.91
|
11.06 h*µg/mL
Standard Deviation 5.41
|
9.15 h*µg/mL
Standard Deviation 4.39
|
13.07 h*µg/mL
Standard Deviation 11.03
|
8.54 h*µg/mL
Standard Deviation 1.96
|
19.88 h*µg/mL
Standard Deviation 4.75
|
|
Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
OSI-420 (n=6,6,6,6,3,3)
|
1.15 h*µg/mL
Standard Deviation 1.21
|
0.48 h*µg/mL
Standard Deviation 0.35
|
0.41 h*µg/mL
Standard Deviation 0.18
|
0.99 h*µg/mL
Standard Deviation 0.73
|
0.36 h*µg/mL
Standard Deviation 0.03
|
1.42 h*µg/mL
Standard Deviation 0.17
|
|
Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
Capecitabine (n=6,6,6,6,3,3)
|
1.43 h*µg/mL
Standard Deviation 1.02
|
1.63 h*µg/mL
Standard Deviation 1.01
|
5.88 h*µg/mL
Standard Deviation 6.28
|
5.28 h*µg/mL
Standard Deviation 3.25
|
13.63 h*µg/mL
Standard Deviation 8.63
|
9.74 h*µg/mL
Standard Deviation 3.02
|
|
Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
5'-DFCR (n=5,5,6,6,3,3)
|
3.97 h*µg/mL
Standard Deviation 2.65
|
7.01 h*µg/mL
Standard Deviation 1.89
|
20.27 h*µg/mL
Standard Deviation 11.53
|
9.35 h*µg/mL
Standard Deviation 3.26
|
12.63 h*µg/mL
Standard Deviation 9.89
|
8.06 h*µg/mL
Standard Deviation 2.14
|
|
Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
5'-DFUR (n=4,5,6,6,3,3)
|
15.42 h*µg/mL
Standard Deviation 9.45
|
13.58 h*µg/mL
Standard Deviation 7.84
|
9.76 h*µg/mL
Standard Deviation 4.60
|
10.86 h*µg/mL
Standard Deviation 4.96
|
5.17 h*µg/mL
Standard Deviation 0.89
|
8.53 h*µg/mL
Standard Deviation 1.87
|
SECONDARY outcome
Timeframe: Month 6Population: Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented.
As per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions (target and non-target lesions) or the unequivocal progression of existing non-target lesions.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From baseline thereafter, every 6 weeks (±7 days), then 1 week after last dose (follow-up), thereafter every 6 weeks (±7 days) until disease progression (up to Week 259)Population: Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented.
A participant was defined as having controlled disease if they sustained a Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) during the assessment. As per RECIST v1.1, CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level; PR is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter; SD for target lesions is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started and SD for non-target lesions defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: One week before start of study treatment and weekly until disease progression or death (Up to Week 259)Population: Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented.
Clinical benefit response was defined as a composite of pain control, Karnofsky performance status (KPS), and weight. The KPS allows participants to be classified as per their functional impairment (abnormal function). It was recorded on an 11-point scale; 0= "dead" to 100= "Normal, no complaints, no evidence of disease" and sub-divided to 3 categories; 0 to 40 = "Unable to care for self, requires institutional or hospital care or equivalent, disease may be rapidly progressing"; 50 to 70= "Unable to work, able to live at home and care for most personal needs, varying amount of assistance needed and 80 to 100= "Able to carry on normal activity; no special care is needed".
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From baseline until death (Up to Week 259)Population: Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented.
Survival was the interval of time from date of first dose of study medication to date of death at any time. Participants who had not died were censored at the date of last contact when they were known to be alive.
Outcome measures
Outcome data not reported
Adverse Events
ERL+BEV+CAP Dose Level-1
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
ERL+BEV+CAP Dose Level-2
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
ERL+BEV+CAP Dose Level-3
Serious events: 4 serious events
Other events: 6 other events
Deaths: 0 deaths
ERL+BEV+CAP Dose Level-4
Serious events: 5 serious events
Other events: 6 other events
Deaths: 0 deaths
ERL+BEV+CAP Dose Level-5
Serious events: 3 serious events
Other events: 3 other events
Deaths: 0 deaths
ERL+BEV+CAP Dose Level-6
Serious events: 3 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ERL+BEV+CAP Dose Level-1
n=6 participants at risk
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
n=6 participants at risk
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
n=6 participants at risk
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
n=6 participants at risk
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
n=3 participants at risk
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
n=3 participants at risk
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Blood and lymphatic system disorders
Bilirubinaemia
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Blood and lymphatic system disorders
Embolism pulmonary
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Blood and lymphatic system disorders
Hyponatremia
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Cardiac disorders
Myocardial infarction
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Haemorrhage rectum
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Intestinal stenosis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Fatigue
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Fever
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Pain
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Syncope
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Infections and infestations
Infection
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Infections and infestations
Sepsis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Musculoskeletal and connective tissue disorders
Skeletal pain
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Nervous system disorders
Aphasia
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Nervous system disorders
Vertigo
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
Other adverse events
| Measure |
ERL+BEV+CAP Dose Level-1
n=6 participants at risk
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-2
n=6 participants at risk
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-3
n=6 participants at risk
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-4
n=6 participants at risk
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-5
n=3 participants at risk
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
ERL+BEV+CAP Dose Level-6
n=3 participants at risk
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m\^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Blood and lymphatic system disorders
Bilirubin
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Blood and lymphatic system disorders
Coagulation time decreased
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Blood and lymphatic system disorders
Epistaxis
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Blood and lymphatic system disorders
Gingival bleeding
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Blood and lymphatic system disorders
Hypocalcaemia
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Blood and lymphatic system disorders
Hypokalaemia
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Blood and lymphatic system disorders
Hypoproteinemia
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Blood and lymphatic system disorders
Thrombosis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Endocrine disorders
Hyperthyroidism
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Abdominal pain
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Constipation
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
2/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Flatulence
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Gastrointestinal disorder nos
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Hematemesis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Hiccup
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Melena
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Mouth dry
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Nausea
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
2/3 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
2/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Esophagitis
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Stomatitis
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Toothache
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Back pain
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Common cold
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Exsiccosis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Fatigue
|
100.0%
6/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
2/3 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
2/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Fever
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Leg pain
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Oedema
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Oedema mouth
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Oedema peripheral
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Pain
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Rigors
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Syncope
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
General disorders
Temperature changed sensation
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Hepatobiliary disorders
Ascites
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Infections and infestations
Herpes simplex
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Infections and infestations
Infection
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Infections and infestations
Moniliasis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Infections and infestations
Skin infection
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Infections and infestations
Wound dehiscence
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Investigations
C- reactive protein positive
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Metabolism and nutrition disorders
Appetite loss
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Metabolism and nutrition disorders
Weight decrease
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Musculoskeletal and connective tissue disorders
Skeletal pain
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Nervous system disorders
Dysphonia
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Nervous system disorders
Headache
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Nervous system disorders
Taste perversion
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Nervous system disorders
Vertigo
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
2/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Psychiatric disorders
Anxiety
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Psychiatric disorders
Depression
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Psychiatric disorders
Sleep disorder
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Renal and urinary disorders
Albuminuria
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Renal and urinary disorders
Urinary tract infection
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Reproductive system and breast disorders
Genital ulceration
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Reproductive system and breast disorders
Vaginitis
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Coughing
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Increased pulmonary secretion
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
2/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Bullous eruption
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Mucosis left breast
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodyesthesia
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
83.3%
5/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Paronychia
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
83.3%
5/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
4/6 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
2/3 • From screening up to 30 days after the last chemotherapy treatment.
|
66.7%
2/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Skin dry
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
50.0%
3/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Skin reaction localized
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Skin and subcutaneous tissue disorders
Sweating increased
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Vascular disorders
Hypertension
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Vascular disorders
Hypertension aggravated
|
33.3%
2/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
16.7%
1/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
|
Vascular disorders
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/6 • From screening up to 30 days after the last chemotherapy treatment.
|
0.00%
0/3 • From screening up to 30 days after the last chemotherapy treatment.
|
33.3%
1/3 • From screening up to 30 days after the last chemotherapy treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER