Trial Outcomes & Findings for Study of Poly (ADP-Ribose) Polymerase (PARP) Inhibitor E7016 in Combination With Temozolomide in Subjects With Advanced Solid Tumors (NCT NCT01127178)
NCT ID: NCT01127178
Last Updated: 2024-10-10
Results Overview
The MTD was defined as the highest dose of E7016 in combination with temozolomide at which no more than one of six participants experienced a dose-limiting toxicity (DLT). DLTs were defined as those adverse events (AEs) considered related to E7016 which occurred during the first cycle of study drug administration. DLTs were evaluated and graded based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version \[v\] 4.0).
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
12 participants
Primary outcome timeframe
Cycle 1 (Cycle length = 28 days)
Results posted on
2024-10-10
Participant Flow
Participants took part in the study at 2 investigative sites in the United States from 29 March 2010 to 24 February 2011.
A total of 13 participants were screened, of which 1 was screen failure and 12 were enrolled to receive study treatment in Dose Escalation Part. The study was terminated due to sponsor's strategic decision, which is unrelated to safety, therefore no participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part of this study.
Participant milestones
| Measure |
Dose Escalation Part: E7016 4 mg/kg/Day + Temozolomide 150 mg/m^2
Participants received single oral dose of 4 milligrams per kilogram per day (mg/kg/day) E7016 capsule on Day -7 for pharmacokinetic (PK) analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 milligrams per square meter (mg/m\^2) capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay greater than (\>) 2 weeks for recovery of toxicity.
|
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2
Participants received single oral dose of 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
|---|---|---|
|
Dose Escalation: Treatment Phase
STARTED
|
9
|
3
|
|
Dose Escalation: Treatment Phase
COMPLETED
|
5
|
3
|
|
Dose Escalation: Treatment Phase
NOT COMPLETED
|
4
|
0
|
|
Dose Escalation: Extension Phase
STARTED
|
5
|
3
|
|
Dose Escalation: Extension Phase
COMPLETED
|
3
|
2
|
|
Dose Escalation: Extension Phase
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Dose Escalation Part: E7016 4 mg/kg/Day + Temozolomide 150 mg/m^2
Participants received single oral dose of 4 milligrams per kilogram per day (mg/kg/day) E7016 capsule on Day -7 for pharmacokinetic (PK) analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 milligrams per square meter (mg/m\^2) capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay greater than (\>) 2 weeks for recovery of toxicity.
|
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2
Participants received single oral dose of 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
|---|---|---|
|
Dose Escalation: Treatment Phase
Adverse Event
|
1
|
0
|
|
Dose Escalation: Treatment Phase
Withdrawal by Subject
|
1
|
0
|
|
Dose Escalation: Treatment Phase
Other
|
2
|
0
|
|
Dose Escalation: Extension Phase
Adverse Event
|
0
|
1
|
|
Dose Escalation: Extension Phase
Withdrawal by Subject
|
1
|
0
|
|
Dose Escalation: Extension Phase
Other
|
1
|
0
|
Baseline Characteristics
Study of Poly (ADP-Ribose) Polymerase (PARP) Inhibitor E7016 in Combination With Temozolomide in Subjects With Advanced Solid Tumors
Baseline characteristics by cohort
| Measure |
Dose Escalation Part: E7016 4 mg/kg/Day + Temozolomide 150 mg/m^2
n=9 Participants
Participants received single oral dose of 4 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2
n=3 Participants
Participants received single oral dose of 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.8 Years
STANDARD_DEVIATION 8.17 • n=99 Participants
|
57.0 Years
STANDARD_DEVIATION 8.19 • n=107 Participants
|
55.3 Years
STANDARD_DEVIATION 7.85 • n=206 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 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
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
10 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
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (Cycle length = 28 days)Population: The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications.
The MTD was defined as the highest dose of E7016 in combination with temozolomide at which no more than one of six participants experienced a dose-limiting toxicity (DLT). DLTs were defined as those adverse events (AEs) considered related to E7016 which occurred during the first cycle of study drug administration. DLTs were evaluated and graded based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version \[v\] 4.0).
Outcome measures
| Measure |
Dose Escalation Part, All Participants: E7016 + Temozolomide
n=12 Participants
Participants received single oral dose of 4 or 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase.
|
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2
Participants received single oral dose of 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
|---|---|---|
|
Maximum Tolerated Dose (MTD) for E7016 in Combination With Temozolomide
|
4 mg/kg/day
|
—
|
PRIMARY outcome
Timeframe: Cycle 1 (Cycle length = 28 days)Population: The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications.
A DLT was defined as those AEs considered related to E7016 which occurred during the first cycle of study drug administration. DLTs were evaluated and graded based on the NCI CTCAE version 4.0. The following toxicities were regarded as DLTs: a Grade 4 hematologic toxicity (lasting \[greater than or equal to\] \>=5 days); a temozolomide dose reduction for Grade \>=3 neutropenia or thrombocytopenia; or a Grade \>=3 nonhematologic toxicity (except optimally managed nausea, vomiting, or diarrhea) that was assessed by the investigator as related to study drug. A participant with two or more DLTs with the same preferred term was counted only once for that preferred term.
Outcome measures
| Measure |
Dose Escalation Part, All Participants: E7016 + Temozolomide
n=9 Participants
Participants received single oral dose of 4 or 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase.
|
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2
n=3 Participants
Participants received single oral dose of 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
|---|---|---|
|
Number of Participants With Dose-limiting Toxicity (DLT)
Tachycardia
|
0 Participants
|
2 Participants
|
|
Number of Participants With Dose-limiting Toxicity (DLT)
Presyncope
|
0 Participants
|
2 Participants
|
|
Number of Participants With Dose-limiting Toxicity (DLT)
Hypotension
|
0 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (Cycle length = 28 days)Population: An ADI was not pursued due to the limited sample size. No data was collected and analyzed to report in this outcome measure.
The ADI determination plan was based primarily on clinical, and/or PK measurements of drug concentration and/or bioactivity as defined by preclinical studies. However, the ADI was not pursued due to the limited sample size.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From Cycle 1 Day 1 up to 6 Cycles (Cycle length=28 days) of treatment, an average of 24 weeksPopulation: The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications.
The ORR was defined as the percentage of participants with complete response (CR) plus partial response (PR) as determined by the investigator, using modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in the evaluation of magnetic resonance imaging/computerized tomography (MRI/CT) scans of targeted lesions and photographs and bone scans if appropriate for the tumor type. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions. ORR = CR + PR
Outcome measures
| Measure |
Dose Escalation Part, All Participants: E7016 + Temozolomide
n=9 Participants
Participants received single oral dose of 4 or 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase.
|
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2
n=3 Participants
Participants received single oral dose of 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
|---|---|---|
|
Objective Response Rate (ORR)
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
SECONDARY outcome
Timeframe: From Cycle 1 Day 1 up to 6 Cycles (Cycle length=28 days) of treatment, an average of 24 weeksPopulation: The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications.
DCR was defined as the percentage of participants who had BOR of CR plus PR plus stable disease (SD). The best observed response (BOR) was defined as the best response recorded from the start of the study treatment until discontinuation from the study. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions. SD was defined as nonCR/non-progressive disease (PD) (NN), for participants with nontarget lesions. The minimum duration of SD was 7 weeks of multiple dose treatment. For participants who did not have target lesions, the response category NN was used instead of SD. DCR = CR + PR + SD greater than or equal to 7 weeks
Outcome measures
| Measure |
Dose Escalation Part, All Participants: E7016 + Temozolomide
n=9 Participants
Participants received single oral dose of 4 or 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase.
|
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2
n=3 Participants
Participants received single oral dose of 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
|---|---|---|
|
Disease Control Rate (DCR)
|
11.1 Percentage of participants
|
66.7 Percentage of participants
|
SECONDARY outcome
Timeframe: From Cycle 1 Day 1 up to 6 Cycles (Cycle length=28 days) of treatment, an average of 24 weeksPopulation: The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications.
OS was defined as the time from the first dose of E7016 until 6 Cycles of treatment or death whichever occurs first.
Outcome measures
| Measure |
Dose Escalation Part, All Participants: E7016 + Temozolomide
n=9 Participants
Participants received single oral dose of 4 or 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase.
|
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2
n=3 Participants
Participants received single oral dose of 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
|---|---|---|
|
Overall Survival (OS)
|
76.0 days
Interval 16.0 to 267.0
|
NA days
Interval 121.0 to
Median and upper limit of 95% Confidence Interval could not be determined due to insufficient number of deaths.
|
Adverse Events
Dose Escalation Part: E7016 4 mg/kg/Day + Temozolomide 150 mg/m^2
Serious events: 5 serious events
Other events: 9 other events
Deaths: 4 deaths
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dose Escalation Part: E7016 4 mg/kg/Day + Temozolomide 150 mg/m^2
n=9 participants at risk
Participants received single oral dose of 4 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2
n=3 participants at risk
Participants received single oral dose of 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
|---|---|---|
|
Gastrointestinal disorders
Ascites
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Gastrointestinal disorders
Gastritis
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
General disorders
Asthenia
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
General disorders
Disease progression
|
22.2%
2/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Infections and infestations
Sepsis
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Metabolism and nutrition disorders
Hypovolemia
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
Other adverse events
| Measure |
Dose Escalation Part: E7016 4 mg/kg/Day + Temozolomide 150 mg/m^2
n=9 participants at risk
Participants received single oral dose of 4 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
Dose Escalation Part: E7016 8 mg/kg/Day + Temozolomide 150 mg/m^2
n=3 participants at risk
Participants received single oral dose of 8 mg/kg/day E7016 capsule on Day -7 for PK analysis, followed by once daily dose from days 1 to 5 in combination with temozolomide 150 mg/m\^2 capsule and alone on days 6 and 7 of Cycle 1 (cycle length=28 days) in Treatment Phase. Participants who completed the Treatment Phase entered the Extension Phase of Dose Escalation Part and continued the treatment in Extension Phase in same manner of Treatment Phase until unacceptable toxicity, disease progression, termination by the treating investigator, withdrawal of consent, termination of the program by the sponsor, or treatment delay \>2 weeks for recovery of toxicity.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
22.2%
2/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Cardiac disorders
Palpitations
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Cardiac disorders
Tachycardia
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
100.0%
3/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Eye disorders
Periorbital oedema
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Eye disorders
Vision blurred
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Gastrointestinal disorders
Addominal tenderness
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Gastrointestinal disorders
Constipation
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Gastrointestinal disorders
Diarrhoea
|
22.2%
2/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
66.7%
2/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Gastrointestinal disorders
Dry mouth
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Gastrointestinal disorders
Haematemesis
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Gastrointestinal disorders
Nausea
|
44.4%
4/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
100.0%
3/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Gastrointestinal disorders
Oesophageal stenosis
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Gastrointestinal disorders
Stomatitis
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Gastrointestinal disorders
Vomiting
|
44.4%
4/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
66.7%
2/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
General disorders
Asthenia
|
22.2%
2/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
General disorders
Chest discomfort
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
General disorders
Fatigue
|
55.6%
5/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
66.7%
2/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Hepatobiliary disorders
Cholelithiasis
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Hepatobiliary disorders
Hepatic steatosis
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Infections and infestations
Candidiasis
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Infections and infestations
Folliculitis
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Infections and infestations
Oral candidiasis
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Investigations
Urine output decreased
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Investigations
Weight decreased
|
22.2%
2/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
22.2%
2/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Metabolism and nutrition disorders
Dehydration
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
66.7%
2/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis of jaw
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Nervous system disorders
Headache
|
33.3%
3/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
66.7%
2/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Nervous system disorders
Paraethesia
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Nervous system disorders
Presyncope
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
66.7%
2/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Nervous system disorders
Restless leg syndrome
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Nervous system disorders
Sinus headache
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Nervous system disorders
Syncope
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Psychiatric disorders
Anxiety
|
22.2%
2/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Psychiatric disorders
Insomnia
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Psychiatric disorders
Mental status change
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
22.2%
2/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
22.2%
2/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea external
|
22.2%
2/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Hyperventilation
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Vascular disorders
Flushing
|
0.00%
0/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Vascular disorders
Hypotension
|
22.2%
2/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
33.3%
1/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
Infections and infestations
Urinary tract infection
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
|
General disorders
Non-cardiac chest pain
|
11.1%
1/9 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
0.00%
0/3 • From date of first dose up to 30 days after the last dose of study drug (up to 45 weeks)
The SAS consisted of all participants who received at least one dose of E7016 or temozolomide and had at least one safety assessment after receiving these medications. As planned, combined safety data for Treatment phase and Extension phase was reported.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER