Trial Outcomes & Findings for Regorafenib+FOLFIRI Versus Placebo+FOLFIRI as 2nd Line Tx in Metastatic Colorectal Cancer (NCT NCT01298570)
NCT ID: NCT01298570
Last Updated: 2021-01-06
Results Overview
To compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients failing one prior oxaliplatin-containing regimen for metastatic colorectal cancer. PFS is defined as the time from randomization until metastatic colorectal cancer (mCRC) progression or death as a result of any cause. Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
181 participants
Primary outcome timeframe
5.5 years
Results posted on
2021-01-06
Participant Flow
224 participants were consented to the study from 39 institutions from 4/7/11 - 8/10/15.
30 participants were ineligible, 7 withdrew prior to beginning protocol therapy, 3 could not participate due to study closure, 2 were unable to participate for financial reasons, 1 did not provide a reason for non-participation; 181 patients were enrolled and went on treatment.
Participant milestones
| Measure |
Arm A
regorafenib 160 mg + FOLFIRI
Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
Arm B
Placebo + FOLFIRI
Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
|---|---|---|
|
Overall Study
STARTED
|
120
|
61
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
120
|
61
|
Reasons for withdrawal
| Measure |
Arm A
regorafenib 160 mg + FOLFIRI
Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
Arm B
Placebo + FOLFIRI
Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
|---|---|---|
|
Overall Study
Disease progression, relapse during acti
|
64
|
40
|
|
Overall Study
Adverse Event
|
20
|
2
|
|
Overall Study
Withdrawal by Subject
|
21
|
6
|
|
Overall Study
Treatment delay > 4 weeks
|
4
|
5
|
|
Overall Study
Physician Decision
|
4
|
2
|
|
Overall Study
Other complicating disease
|
2
|
1
|
|
Overall Study
Surgery
|
2
|
1
|
|
Overall Study
Symptomatic progression/deterioration
|
3
|
2
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Ineligibility
|
0
|
1
|
Baseline Characteristics
Regorafenib+FOLFIRI Versus Placebo+FOLFIRI as 2nd Line Tx in Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Arm A
n=120 Participants
regorafenib 160 mg + FOLFIRI
Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
Arm B
n=61 Participants
Placebo + FOLFIRI
Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
Total
n=181 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62 years
n=99 Participants
|
62 years
n=107 Participants
|
62 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
52 Participants
n=99 Participants
|
29 Participants
n=107 Participants
|
81 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
68 Participants
n=99 Participants
|
32 Participants
n=107 Participants
|
100 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
20 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
31 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
99 Participants
n=99 Participants
|
48 Participants
n=107 Participants
|
147 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
84 count of participants
n=99 Participants
|
43 count of participants
n=107 Participants
|
127 count of participants
n=206 Participants
|
|
Region of Enrollment
Ireland
|
36 count of participants
n=99 Participants
|
18 count of participants
n=107 Participants
|
54 count of participants
n=206 Participants
|
|
ECOG Performance Status
0
|
52 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
75 Participants
n=206 Participants
|
|
ECOG Performance Status
1
|
68 Participants
n=99 Participants
|
38 Participants
n=107 Participants
|
106 Participants
n=206 Participants
|
|
Stage at diagnosis
I
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Stage at diagnosis
II
|
4 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Stage at diagnosis
III
|
24 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
|
Stage at diagnosis
IV
|
86 Participants
n=99 Participants
|
46 Participants
n=107 Participants
|
132 Participants
n=206 Participants
|
|
Stage at diagnosis
Unknown
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Prior Biologic Agent
None
|
33 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
49 Participants
n=206 Participants
|
|
Prior Biologic Agent
Bevacizumab
|
76 Participants
n=99 Participants
|
41 Participants
n=107 Participants
|
117 Participants
n=206 Participants
|
|
Prior Biologic Agent
EGFR inhibitor
|
11 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
|
Locally Reported RAS
Wildtype
|
49 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
67 Participants
n=206 Participants
|
|
Locally Reported RAS
Mutated
|
54 Participants
n=99 Participants
|
37 Participants
n=107 Participants
|
91 Participants
n=206 Participants
|
|
Locally Reported RAS
Unknown
|
17 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
|
Locally Reported BRAF
Wildtype
|
22 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Locally Reported BRAF
Mutated
|
10 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Locally Reported BRAF
Unknown
|
88 Participants
n=99 Participants
|
47 Participants
n=107 Participants
|
135 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 5.5 yearsTo compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients failing one prior oxaliplatin-containing regimen for metastatic colorectal cancer. PFS is defined as the time from randomization until metastatic colorectal cancer (mCRC) progression or death as a result of any cause. Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Outcome measures
| Measure |
Arm A
n=120 Participants
regorafenib 160 mg + FOLFIRI
Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
Arm B
n=61 Participants
Placebo + FOLFIRI
Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
|---|---|---|
|
Progression Free Survival (PFS)
|
6.1 Months
Interval 5.5 to 7.3
|
5.3 Months
Interval 4.1 to 6.0
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: Only evaluable participants (those who had RECIST measurements after baseline) were included in this analysis
To compare overall response (OR) rates (OR= CR + PR) between ARM A and ARM B as defined via Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Arm A
n=102 Participants
regorafenib 160 mg + FOLFIRI
Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
Arm B
n=58 Participants
Placebo + FOLFIRI
Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
|---|---|---|
|
Overall Response(OR)Rate
Complete Response (CR)
|
0 Participants
|
0 Participants
|
|
Overall Response(OR)Rate
Partial Response (PR)
|
35 Participants
|
12 Participants
|
|
Overall Response(OR)Rate
Other
|
67 Participants
|
46 Participants
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: Only evaluable participants (those who had RECIST measurements after baseline) were included in this analysis
To compare Disease Control (DC) Rate (DC= CR + PR + SD) between ARM A and ARM B as defined via Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions and Stable Disease (SD) ), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Outcome measures
| Measure |
Arm A
n=102 Participants
regorafenib 160 mg + FOLFIRI
Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
Arm B
n=58 Participants
Placebo + FOLFIRI
Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
|---|---|---|
|
Disease Control (DC) Rate
Disease Control Total (CR+PR+SD)
|
84 Participants
|
43 Participants
|
|
Disease Control (DC) Rate
Progression
|
18 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: 5.5 yearsTo compare overall survival (OS) between ARM A and ARM B. OS is defined as the time from randomization until death as a result of any cause.
Outcome measures
| Measure |
Arm A
n=120 Participants
regorafenib 160 mg + FOLFIRI
Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
Arm B
n=61 Participants
Placebo + FOLFIRI
Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
|---|---|---|
|
Overall Survival (OS)
|
13.8 Months
Interval 10.5 to 14.8
|
11.7 Months
Interval 9.0 to 15.9
|
SECONDARY outcome
Timeframe: 28 daysPopulation: This objective was designed to only look at a small subset of participants (11 on each arm)
To compare the pharmacokinetic (PK) profile of FOLFIRI between a subset of patients receiving regorafenib (ARM A) and patients receiving placebo (Arm B). The Area Under the Curve (AUC) levels of the irinotecan metabolite SN-38 were compared.
Outcome measures
| Measure |
Arm A
n=11 Participants
regorafenib 160 mg + FOLFIRI
Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
Arm B
n=11 Participants
Placebo + FOLFIRI
Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
|---|---|---|
|
Drug Metabolism
Cycle 1
|
0.68 AUC/dose=(ng/mL*h)/(mg/m^2)
Interval 0.49 to 0.89
|
0.63 AUC/dose=(ng/mL*h)/(mg/m^2)
Interval 0.47 to 0.91
|
|
Drug Metabolism
Cycle 2
|
0.59 AUC/dose=(ng/mL*h)/(mg/m^2)
Interval 0.24 to 0.85
|
0.72 AUC/dose=(ng/mL*h)/(mg/m^2)
Interval 0.47 to 0.91
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: All patients who received treatment
Toxicity Assessments were made according to NCI CTCAE v. 4.0 . Severe events (grades 3-4) that occurred in a higher percentage of regorafenib treated participants as compared to placebo are reported below.
Outcome measures
| Measure |
Arm A
n=120 Participants
regorafenib 160 mg + FOLFIRI
Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
Arm B
n=61 Participants
Placebo + FOLFIRI
Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
|---|---|---|
|
Percentage of Patients With Severe Adverse Events
neutropenia
|
41 percentage of participants
|
30 percentage of participants
|
|
Percentage of Patients With Severe Adverse Events
diarrhea
|
15 percentage of participants
|
5 percentage of participants
|
|
Percentage of Patients With Severe Adverse Events
hypophosphatemia
|
14 percentage of participants
|
0 percentage of participants
|
|
Percentage of Patients With Severe Adverse Events
hypertension
|
8 percentage of participants
|
2 percentage of participants
|
|
Percentage of Patients With Severe Adverse Events
elevated lipase
|
8 percentage of participants
|
3 percentage of participants
|
Adverse Events
Arm A
Serious events: 60 serious events
Other events: 118 other events
Deaths: 112 deaths
Arm B
Serious events: 20 serious events
Other events: 61 other events
Deaths: 59 deaths
Serious adverse events
| Measure |
Arm A
n=120 participants at risk
regorafenib 160 mg + FOLFIRI
Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
Arm B
n=61 participants at risk
Placebo + FOLFIRI
Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
|---|---|---|
|
Infections and infestations
Abdominal infection
|
0.83%
1/120
|
0.00%
0/61
|
|
Gastrointestinal disorders
Abdominal pain
|
7.5%
9/120
|
3.3%
2/61
|
|
Blood and lymphatic system disorders
Anemia
|
1.7%
2/120
|
4.9%
3/61
|
|
Renal and urinary disorders
Acute kidney injury
|
0.83%
1/120
|
0.00%
0/61
|
|
Investigations
Alanine aminotransferase increased
|
0.83%
1/120
|
0.00%
0/61
|
|
Investigations
Alkaline phosphatase increased
|
0.83%
1/120
|
0.00%
0/61
|
|
Metabolism and nutrition disorders
Anorexia
|
2.5%
3/120
|
1.6%
1/61
|
|
Infections and infestations
Anorectal infection
|
0.00%
0/120
|
1.6%
1/61
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/120
|
1.6%
1/61
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/120
|
1.6%
1/61
|
|
Cardiac disorders
Chest pain - cardiac
|
1.7%
2/120
|
1.6%
1/61
|
|
General disorders
Chills
|
0.00%
0/120
|
1.6%
1/61
|
|
Investigations
Aspartate aminotransferase increased
|
0.83%
1/120
|
0.00%
0/61
|
|
Cardiac disorders
Atrial fibrillation
|
0.83%
1/120
|
0.00%
0/61
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.83%
1/120
|
0.00%
0/61
|
|
Investigations
Blood bilirubin increased
|
0.83%
1/120
|
0.00%
0/61
|
|
Cardiac disorders
Sinus bradicardia
|
0.83%
1/120
|
0.00%
0/61
|
|
Infections and infestations
Catheter related infection
|
0.83%
1/120
|
0.00%
0/61
|
|
Infections and infestations
Cecal infection
|
0.83%
1/120
|
0.00%
0/61
|
|
Hepatobiliary disorders
Cholecystitis
|
2.5%
3/120
|
1.6%
1/61
|
|
Gastrointestinal disorders
Colitis
|
0.83%
1/120
|
0.00%
0/61
|
|
Gastrointestinal disorders
Constipation
|
0.83%
1/120
|
3.3%
2/61
|
|
Gastrointestinal disorders
Colonic hemorrhage
|
0.83%
1/120
|
0.00%
0/61
|
|
Gastrointestinal disorders
Colonic obstruction
|
0.83%
1/120
|
0.00%
0/61
|
|
Gastrointestinal disorders
Colonic perforation
|
0.83%
1/120
|
0.00%
0/61
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.83%
1/120
|
0.00%
0/61
|
|
General disorders
Death NOS
|
1.7%
2/120
|
3.3%
2/61
|
|
Metabolism and nutrition disorders
Dehydration
|
4.2%
5/120
|
4.9%
3/61
|
|
Gastrointestinal disorders
Diarrhea
|
8.3%
10/120
|
1.6%
1/61
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.5%
3/120
|
1.6%
1/61
|
|
Infections and infestations
Enterocolitis infectious
|
0.00%
0/120
|
1.6%
1/61
|
|
Gastrointestinal disorders
Esophageal varices hemorrhage
|
0.00%
0/120
|
1.6%
1/61
|
|
General disorders
Fatigue
|
1.7%
2/120
|
1.6%
1/61
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.8%
7/120
|
4.9%
3/61
|
|
Injury, poisoning and procedural complications
Fall
|
1.7%
2/120
|
0.00%
0/61
|
|
General disorders
Fever
|
7.5%
9/120
|
4.9%
3/61
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/120
|
1.6%
1/61
|
|
Infections and infestations
Infections and infestations - Other, specify
|
0.00%
0/120
|
1.6%
1/61
|
|
Infections and infestations
Lung infection
|
1.7%
2/120
|
0.00%
0/61
|
|
General disorders
flu like symptoms
|
0.83%
1/120
|
0.00%
0/61
|
|
General disorders
Pressure in Head
|
0.83%
1/120
|
0.00%
0/61
|
|
General disorders
Rigors
|
0.83%
1/120
|
0.00%
0/61
|
|
General disorders
Generalized muscle weakness
|
0.83%
1/120
|
0.00%
0/61
|
|
Investigations
GGT increased
|
0.83%
1/120
|
0.00%
0/61
|
|
Nervous system disorders
Headache
|
0.83%
1/120
|
0.00%
0/61
|
|
Hepatobiliary disorders
Hepatic failure
|
0.83%
1/120
|
0.00%
0/61
|
|
Hepatobiliary disorders
Cholangitis
|
0.83%
1/120
|
0.00%
0/61
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.83%
1/120
|
0.00%
0/61
|
|
Vascular disorders
Hypertension
|
0.83%
1/120
|
0.00%
0/61
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.83%
1/120
|
0.00%
0/61
|
|
Gastrointestinal disorders
Ileus
|
2.5%
3/120
|
0.00%
0/61
|
|
Nervous system disorders
Movements involuntary
|
0.00%
0/120
|
1.6%
1/61
|
|
Gastrointestinal disorders
Mucositis oral
|
2.5%
3/120
|
1.6%
1/61
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/120
|
1.6%
1/61
|
|
Gastrointestinal disorders
Nausea
|
1.7%
2/120
|
1.6%
1/61
|
|
General disorders
Pain
|
0.83%
1/120
|
1.6%
1/61
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/120
|
1.6%
1/61
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/120
|
1.6%
1/61
|
|
Infections and infestations
Skin infection
|
0.00%
0/120
|
1.6%
1/61
|
|
Surgical and medical procedures
Surgical and medical procedures - Other, specify
|
0.00%
0/120
|
1.6%
1/61
|
|
Vascular disorders
Thromboembolic event
|
2.5%
3/120
|
3.3%
2/61
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/120
|
1.6%
1/61
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/120
|
3.3%
2/61
|
|
Infections and infestations
Infection of unknown source
|
0.83%
1/120
|
0.00%
0/61
|
|
General disorders
Infusion related reaction
|
0.83%
1/120
|
0.00%
0/61
|
|
Psychiatric disorders
Insomnia
|
0.83%
1/120
|
0.00%
0/61
|
|
Injury, poisoning and procedural complications
Intestinal stoma site bleeding
|
0.83%
1/120
|
0.00%
0/61
|
|
Investigations
Obstructive Jaundice
|
0.83%
1/120
|
0.00%
0/61
|
|
Investigations
Deteriorating LFT's
|
0.83%
1/120
|
0.00%
0/61
|
|
Investigations
Elevated INR
|
0.83%
1/120
|
0.00%
0/61
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
0.83%
1/120
|
0.00%
0/61
|
|
Metabolism and nutrition disorders
severely elevated lipase level
|
0.83%
1/120
|
0.00%
0/61
|
|
Metabolism and nutrition disorders
Malnutrician
|
0.83%
1/120
|
0.00%
0/61
|
|
Investigations
Neutrophil count decreased
|
5.0%
6/120
|
0.00%
0/61
|
|
General disorders
Non-cardiac chest pain
|
0.83%
1/120
|
0.00%
0/61
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
0.83%
1/120
|
0.00%
0/61
|
|
Cardiac disorders
Palpitations
|
0.83%
1/120
|
0.00%
0/61
|
|
Investigations
Platelet count decreased
|
1.7%
2/120
|
0.00%
0/61
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.83%
1/120
|
0.00%
0/61
|
|
Psychiatric disorders
Psychosis
|
0.83%
1/120
|
0.00%
0/61
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
3.3%
4/120
|
0.00%
0/61
|
|
Infections and infestations
Sepsis
|
1.7%
2/120
|
0.00%
0/61
|
|
Skin and subcutaneous tissue disorders
right hip abscess
|
0.83%
1/120
|
0.00%
0/61
|
|
Gastrointestinal disorders
Small intestinal perforation
|
0.83%
1/120
|
0.00%
0/61
|
|
Infections and infestations
Soft tissue infection
|
1.7%
2/120
|
0.00%
0/61
|
|
Injury, poisoning and procedural complications
Stomal ulcer
|
0.83%
1/120
|
0.00%
0/61
|
|
Nervous system disorders
Syncope
|
0.83%
1/120
|
0.00%
0/61
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
0.83%
1/120
|
0.00%
0/61
|
|
Infections and infestations
Upper respiratory infection
|
0.83%
1/120
|
0.00%
0/61
|
|
Cardiac disorders
Ventricular tachycardia
|
0.83%
1/120
|
0.00%
0/61
|
Other adverse events
| Measure |
Arm A
n=120 participants at risk
regorafenib 160 mg + FOLFIRI
Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
Arm B
n=61 participants at risk
Placebo + FOLFIRI
Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +
FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
34.2%
41/120
|
14.8%
9/61
|
|
Investigations
Activated partial thromboplastin time prolonged
|
5.8%
7/120
|
4.9%
3/61
|
|
Investigations
Alanine aminotransferase increased
|
25.0%
30/120
|
14.8%
9/61
|
|
Investigations
Alkaline phosphatase increased
|
29.2%
35/120
|
23.0%
14/61
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
25.0%
30/120
|
24.6%
15/61
|
|
Blood and lymphatic system disorders
Anemia
|
55.8%
67/120
|
62.3%
38/61
|
|
Metabolism and nutrition disorders
Anorexia
|
35.8%
43/120
|
11.5%
7/61
|
|
Psychiatric disorders
Anxiety
|
5.0%
6/120
|
1.6%
1/61
|
|
Investigations
Aspartate aminotransferase increased
|
23.3%
28/120
|
16.4%
10/61
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
12/120
|
6.6%
4/61
|
|
Investigations
Blood bilirubin increased
|
18.3%
22/120
|
6.6%
4/61
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
5.0%
6/120
|
0.00%
0/61
|
|
Gastrointestinal disorders
Constipation
|
34.2%
41/120
|
27.9%
17/61
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
15/120
|
6.6%
4/61
|
|
Investigations
Creatinine increased
|
5.0%
6/120
|
8.2%
5/61
|
|
Metabolism and nutrition disorders
Dehydration
|
12.5%
15/120
|
8.2%
5/61
|
|
Psychiatric disorders
Depression
|
7.5%
9/120
|
8.2%
5/61
|
|
Gastrointestinal disorders
Diarrhea
|
52.5%
63/120
|
45.9%
28/61
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
12.5%
15/120
|
8.2%
5/61
|
|
Nervous system disorders
Dizziness
|
7.5%
9/120
|
1.6%
1/61
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
18.3%
22/120
|
11.5%
7/61
|
|
Gastrointestinal disorders
Dysgeusia
|
5.0%
6/120
|
3.3%
2/61
|
|
Gastrointestinal disorders
Dyspepsia
|
7.5%
9/120
|
1.6%
1/61
|
|
Gastrointestinal disorders
Dysphagia
|
5.0%
6/120
|
1.6%
1/61
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.5%
9/120
|
3.3%
2/61
|
|
General disorders
Edema limbs
|
4.2%
5/120
|
6.6%
4/61
|
|
General disorders
Fatigue
|
63.3%
76/120
|
54.1%
33/61
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.8%
7/120
|
1.6%
1/61
|
|
General disorders
Fever
|
15.0%
18/120
|
4.9%
3/61
|
|
Nervous system disorders
Headache
|
20.0%
24/120
|
9.8%
6/61
|
|
General disorders
Flu like symptoms
|
5.8%
7/120
|
1.6%
1/61
|
|
Renal and urinary disorders
Hematuria
|
7.5%
9/120
|
4.9%
3/61
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
14.2%
17/120
|
26.2%
16/61
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
12.5%
15/120
|
0.00%
0/61
|
|
Gastrointestinal disorders
Hemorrhoids
|
8.3%
10/120
|
3.3%
2/61
|
|
Vascular disorders
Hypertension
|
19.2%
23/120
|
14.8%
9/61
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
20.8%
25/120
|
31.1%
19/61
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
30.8%
37/120
|
23.0%
14/61
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
4.2%
5/120
|
11.5%
7/61
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
24.2%
29/120
|
16.4%
10/61
|
|
Metabolism and nutrition disorders
Hypokalemia
|
33.3%
40/120
|
31.1%
19/61
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
13.3%
16/120
|
14.8%
9/61
|
|
Metabolism and nutrition disorders
Hyponatremia
|
16.7%
20/120
|
21.3%
13/61
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
31.7%
38/120
|
9.8%
6/61
|
|
Vascular disorders
Hypotension
|
8.3%
10/120
|
4.9%
3/61
|
|
Endocrine disorders
Hypothyroidism
|
6.7%
8/120
|
1.6%
1/61
|
|
Investigations
INR increased
|
5.0%
6/120
|
8.2%
5/61
|
|
Psychiatric disorders
Insomnia
|
10.8%
13/120
|
4.9%
3/61
|
|
Investigations
Lipase increased
|
17.5%
21/120
|
21.3%
13/61
|
|
Investigations
Lymphocyte count decreased
|
12.5%
15/120
|
18.0%
11/61
|
|
Gastrointestinal disorders
Mucositis oral
|
54.2%
65/120
|
32.8%
20/61
|
|
Gastrointestinal disorders
Nausea
|
50.0%
60/120
|
55.7%
34/61
|
|
Investigations
Neutrophil count decreased
|
57.5%
69/120
|
59.0%
36/61
|
|
Gastrointestinal disorders
Oral pain
|
6.7%
8/120
|
0.00%
0/61
|
|
General disorders
Pain
|
21.7%
26/120
|
6.6%
4/61
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.7%
8/120
|
4.9%
3/61
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
29.2%
35/120
|
9.8%
6/61
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
23.3%
28/120
|
13.1%
8/61
|
|
Investigations
Platelet count decreased
|
28.3%
34/120
|
14.8%
9/61
|
|
Renal and urinary disorders
Proteinuria
|
15.0%
18/120
|
23.0%
14/61
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
15.0%
18/120
|
8.2%
5/61
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
10.0%
12/120
|
3.3%
2/61
|
|
Gastrointestinal disorders
Rectal pain
|
8.3%
10/120
|
1.6%
1/61
|
|
Investigations
Serum amylase increased
|
13.3%
16/120
|
13.1%
8/61
|
|
Cardiac disorders
Sinus tachycardia
|
5.0%
6/120
|
3.3%
2/61
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
9.2%
11/120
|
1.6%
1/61
|
|
Infections and infestations
Urinary tract infection
|
9.2%
11/120
|
4.9%
3/61
|
|
Vascular disorders
Thromboembolic event
|
8.3%
10/120
|
1.6%
1/61
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
40/120
|
16.4%
10/61
|
|
Investigations
Weight loss
|
22.5%
27/120
|
8.2%
5/61
|
|
Investigations
White blood cell decreased
|
29.2%
35/120
|
37.7%
23/61
|
Additional Information
Robin V. Johnson
UNC Lineberger Comprehensive Cancer Center
Phone: 919-966-1125
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place