Trial Outcomes & Findings for Dasatinib or Placebo, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme (NCT NCT00869401)
NCT ID: NCT00869401
Last Updated: 2020-02-13
Results Overview
Overall survival (OS) is the primary endpoint and is defined as the time from study registration to time of death due to any cause. All patients who meet the eligibility criteria, have signed a consent form, and have received at least one dose of the regimens will be considered evaluable. Patients who are lost to follow-up will be censored at the date of their last follow-up. Patients still alive at the time of analysis will be censored. Only Phase II was evaluated for survival
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
217 participants
Primary outcome timeframe
Up to 5 years post treatment
Results posted on
2020-02-13
Participant Flow
Participant milestones
| Measure |
Dose Level 0 Phase I
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 50 mg twice a day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 100 mg/day until progression.
|
Dose Level 0-A Phase I
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 100 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 100 mg/day until progression.
|
Dose Level 1 Phase I
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 1 (Phase II) Dasatinib + Radiation + Temozolomide
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 2 (Phase II) Placebo + Radiation + Temozolomide
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Placebo 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Placebo. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Placebo 150 mg/day until progression.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
7
|
138
|
66
|
|
Overall Study
COMPLETED
|
3
|
3
|
7
|
133
|
63
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
5
|
3
|
Reasons for withdrawal
| Measure |
Dose Level 0 Phase I
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 50 mg twice a day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 100 mg/day until progression.
|
Dose Level 0-A Phase I
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 100 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 100 mg/day until progression.
|
Dose Level 1 Phase I
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 1 (Phase II) Dasatinib + Radiation + Temozolomide
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 2 (Phase II) Placebo + Radiation + Temozolomide
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Placebo 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Placebo. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Placebo 150 mg/day until progression.
|
|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
5
|
3
|
Baseline Characteristics
Dasatinib or Placebo, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
Baseline characteristics by cohort
| Measure |
Phase I
n=13 Participants
All patients included in the Phase I portion of the study were published together for this results portion.
|
Group 1 (Phase II) Dasatinib + Radiation + Temozolomide
n=133 Participants
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 2 (Phase II) Placebo + Radiation + Temozolomide
n=63 Participants
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Placebo 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Placebo. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Placebo 150 mg/day until progression.
|
Total
n=209 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
55.3 Years
STANDARD_DEVIATION 12.9 • n=5 Participants
|
56.8 Years
STANDARD_DEVIATION 11 • n=7 Participants
|
58.2 Years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
58 Years
STANDARD_DEVIATION 11.4 • n=4 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
79 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
81 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
130 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=5 Participants
|
133 participants
n=7 Participants
|
63 participants
n=5 Participants
|
209 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to 5 years post treatmentOverall survival (OS) is the primary endpoint and is defined as the time from study registration to time of death due to any cause. All patients who meet the eligibility criteria, have signed a consent form, and have received at least one dose of the regimens will be considered evaluable. Patients who are lost to follow-up will be censored at the date of their last follow-up. Patients still alive at the time of analysis will be censored. Only Phase II was evaluated for survival
Outcome measures
| Measure |
Group 1 (Phase II) Dasatinib + Radiation + Temozolomide
n=138 Participants
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 2 (Phase II) Placebo + Radiation + Temozolomide
n=66 Participants
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Placebo 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Placebo. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Placebo 150 mg/day until progression.
|
Dose Level 1 Phase I
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
|---|---|---|---|
|
Overall Survival
|
15.6 Months
Interval 14.4 to 19.6
|
19.3 Months
Interval 16.1 to 21.7
|
—
|
PRIMARY outcome
Timeframe: Every cycle from first dose to end of rest period prior cycle 3Population: Only Phase I patients were evaluated for maximum tolerable dose.
Doselimiting toxicity will be defined as: Adverse event at least possibly related to the study medication. All by CTCAE v3.0 criteria: Greater than or equal to grade 3: diarrhea or skin rash or desquamation or (other) clinically relevant non-hematological adverse event or non-hematologic adverse event at least possibly due to drug therapy. Or greater than or equal to grade 4: neutropenia or leukopenia or thrombocytopenia or radiation dermatitis or hematologic adverse event OR failure to administer greater than 75% of dasatinib TMZ or interruption of RT for more than 5 days due to adverse events.OR severe acute central nervous system deterioration attributable to TMZ, RT and or dasatinib which cannot be controlled with corticosteroid administration. The MTD for this study will be defined as the highest safely tolerated dose level where at most 1 out of 6 patients experience DLT with the next higher dose having at least 2 patients out of a maximum of 6 patients experience DLT.
Outcome measures
| Measure |
Group 1 (Phase II) Dasatinib + Radiation + Temozolomide
n=3 Participants
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 2 (Phase II) Placebo + Radiation + Temozolomide
n=3 Participants
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Placebo 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Placebo. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Placebo 150 mg/day until progression.
|
Dose Level 1 Phase I
n=7 Participants
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
|---|---|---|---|
|
The Number of Dose Limiting Toxicities(DLT) in Order to Determine Maximum Tolerable Dose(MTD) of Dasatinib Combined With Radiation and Temozolomide in This Patient Population.
|
1 participants with Dose Limiting Toxicits
|
0 participants with Dose Limiting Toxicits
|
1 participants with Dose Limiting Toxicits
|
SECONDARY outcome
Timeframe: Up to 5 years post treatmentPopulation: All patients meeting the eligibility criteria that have signed a consent form and begun treatment will be considered evaluable
Progression-free survival (PFS) is defined as the time from study registration to the date of first observation of disease progression or death due to any cause (whichever comes first). If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up. Only Phase II patients were evaluated for Progression-free survival
Outcome measures
| Measure |
Group 1 (Phase II) Dasatinib + Radiation + Temozolomide
n=138 Participants
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 2 (Phase II) Placebo + Radiation + Temozolomide
n=66 Participants
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Placebo 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Placebo. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Placebo 150 mg/day until progression.
|
Dose Level 1 Phase I
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
|---|---|---|---|
|
Progression-free Survival
|
6.2 Months
Interval 4.4 to 8.2
|
7.8 Months
Interval 6.5 to 10.9
|
—
|
SECONDARY outcome
Timeframe: Up to 5 years post treatmentPopulation: Participants that have at least one disease evaluation for assessing best response to treatment.
Objective response to treatment will be determined by a combination of the results of neurological exam and the MRI and/or CT measurement of the tumor at each evaluation as is used for all NCCTG neuro-oncology trials. The proportion of patients in each response category will be summarized. Only phase II patients were evaluated for response.
Outcome measures
| Measure |
Group 1 (Phase II) Dasatinib + Radiation + Temozolomide
n=98 Participants
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 2 (Phase II) Placebo + Radiation + Temozolomide
n=48 Participants
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Placebo 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Placebo. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Placebo 150 mg/day until progression.
|
Dose Level 1 Phase I
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
|---|---|---|---|
|
Objective Response
Progression
|
.31 Proportion of participants
|
.19 Proportion of participants
|
—
|
|
Objective Response
Stable
|
.59 Proportion of participants
|
.73 Proportion of participants
|
—
|
|
Objective Response
REGR
|
.08 Proportion of participants
|
.02 Proportion of participants
|
—
|
|
Objective Response
Partial Response
|
.02 Proportion of participants
|
.06 Proportion of participants
|
—
|
|
Objective Response
Complete Response
|
0 Proportion of participants
|
0 Proportion of participants
|
—
|
Adverse Events
Dose Level 0 Phase I
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Dose Level 0-A Phase I
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Dose Level 1 Phase1
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Group 2 (Phase II) Placebo + Radiation + Temozolomide
Serious events: 52 serious events
Other events: 133 other events
Deaths: 0 deaths
Group 1 (Phase II) Dasatinib + Radiation + Temozolomide
Serious events: 23 serious events
Other events: 62 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dose Level 0 Phase I
n=3 participants at risk
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 100 mg twice a day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 100 mg/day until progression.
|
Dose Level 0-A Phase I
n=3 participants at risk
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 100 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib100 mg/day until progression.
|
Dose Level 1 Phase1
n=7 participants at risk
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 2 (Phase II) Placebo + Radiation + Temozolomide
n=133 participants at risk
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 1 (Phase II) Dasatinib + Radiation + Temozolomide
n=63 participants at risk
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Placebo 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Placebo. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Placebo 150 mg/day until progression.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/7
|
4.5%
6/133 • Number of events 6
|
0.00%
0/63
|
|
Cardiac disorders
Atrial fibrillation
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
0.00%
0/63
|
|
Cardiac disorders
Left ventricular failure
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Gastrointestinal disorders
Colonic perforation
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
3.8%
5/133 • Number of events 5
|
1.6%
1/63 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
General disorders
Death
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
General disorders
Disease progression
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
General disorders
Edema limbs
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
General disorders
Fatigue
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
3.8%
5/133 • Number of events 5
|
0.00%
0/63
|
|
General disorders
Gait abnormal
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
General disorders
Localized edema
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Immune system disorders
Immune system disorder
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Infections and infestations
Encephalitis infection
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Infections and infestations
Sepsis
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Infections and infestations
Skin infection
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
1/3 • Number of events 2
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Investigations
Bilirubin increased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Investigations
Cardiac troponin T increased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Investigations
Creatinine increased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
2.3%
3/133 • Number of events 3
|
1.6%
1/63 • Number of events 1
|
|
Investigations
Leukocyte count decreased
|
66.7%
2/3 • Number of events 2
|
0.00%
0/3
|
0.00%
0/7
|
3.8%
5/133 • Number of events 5
|
7.9%
5/63 • Number of events 6
|
|
Investigations
Lymphocyte count decreased
|
66.7%
2/3 • Number of events 2
|
0.00%
0/3
|
0.00%
0/7
|
9.0%
12/133 • Number of events 13
|
12.7%
8/63 • Number of events 11
|
|
Investigations
Neutrophil count decreased
|
66.7%
2/3 • Number of events 2
|
0.00%
0/3
|
0.00%
0/7
|
3.8%
5/133 • Number of events 6
|
12.7%
8/63 • Number of events 9
|
|
Investigations
Platelet count decreased
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/7
|
6.8%
9/133 • Number of events 9
|
4.8%
3/63 • Number of events 3
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
3.0%
4/133 • Number of events 4
|
1.6%
1/63 • Number of events 1
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
2.3%
3/133 • Number of events 3
|
0.00%
0/63
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
4.5%
6/133 • Number of events 6
|
1.6%
1/63 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Metabolism and nutrition disorders
Serum potassium increased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
1.6%
1/63 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
4.5%
6/133 • Number of events 7
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness left-sided
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness right-sided
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 2
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Ataxia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
Nervous system disorders
Cognitive disturbance
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
2.3%
3/133 • Number of events 5
|
0.00%
0/63
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
3.0%
4/133 • Number of events 5
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Headache
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
Nervous system disorders
Intracranial hemorrhage
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Ischemia cerebrovascular
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 2
|
0.00%
0/63
|
|
Nervous system disorders
Neurological disorder NOS
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 4
|
0.00%
0/63
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Nervous system disorders
Seizure
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
2.3%
3/133 • Number of events 4
|
3.2%
2/63 • Number of events 2
|
|
Nervous system disorders
Syncope
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Trigeminal nerve disorder
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Psychiatric disorders
Confusion
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
3.0%
4/133 • Number of events 4
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
2.3%
3/133 • Number of events 3
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorder
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
2.3%
3/133 • Number of events 3
|
1.6%
1/63 • Number of events 2
|
|
Vascular disorders
Hypertension
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Vascular disorders
Hypotension
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
1.6%
1/63 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
3.2%
2/63 • Number of events 2
|
Other adverse events
| Measure |
Dose Level 0 Phase I
n=3 participants at risk
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 100 mg twice a day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 100 mg/day until progression.
|
Dose Level 0-A Phase I
n=3 participants at risk
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 100 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib100 mg/day until progression.
|
Dose Level 1 Phase1
n=7 participants at risk
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib at 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 2 (Phase II) Placebo + Radiation + Temozolomide
n=133 participants at risk
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Dasatinib 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Dasatinib. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Dasatinib 150 mg/day until progression.
|
Group 1 (Phase II) Dasatinib + Radiation + Temozolomide
n=63 participants at risk
Cycle 1: Radiation therapy (RT) 60 Gy (2 Gy x 30 fractions) 5 days/week on weekdays for 6 weeks. Temozolomide (TMZ) 75 mg/m2/day and Placebo 150 mg/day starting with, and continuing through, RT. Cycle 2: 4-6 week rest period post RT/TMZ/Placebo. Cycles 3-8: (28-day cycles): TMZ 150 mg/m2 days 1-5 of cycle 3 and 200 mg/m2 days 1-5 of cycles 4-8. Cycle 3+: Placebo 150 mg/day until progression.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Blood disorder
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
66.7%
2/3 • Number of events 12
|
66.7%
2/3 • Number of events 10
|
85.7%
6/7 • Number of events 37
|
80.5%
107/133 • Number of events 379
|
65.1%
41/63 • Number of events 135
|
|
Cardiac disorders
Cardiac pain
|
0.00%
0/3
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/133
|
0.00%
0/63
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Ear and labyrinth disorders
Hearing loss
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
4.8%
3/63 • Number of events 4
|
|
Ear and labyrinth disorders
Hearing test abnormal
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 2
|
|
Eye disorders
Diplopia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Eye disorders
Extraocular muscle paresis
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Eye disorders
Eye disorder
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 3
|
0.00%
0/63
|
|
Eye disorders
Keratitis
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Eye disorders
Photophobia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
7.5%
10/133 • Number of events 13
|
11.1%
7/63 • Number of events 11
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
14.3%
1/7 • Number of events 1
|
31.6%
42/133 • Number of events 61
|
20.6%
13/63 • Number of events 16
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
3.8%
5/133 • Number of events 5
|
1.6%
1/63 • Number of events 1
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 2
|
0.00%
0/63
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
2.3%
3/133 • Number of events 3
|
0.00%
0/63
|
|
Gastrointestinal disorders
Esophageal pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 2
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Gastrointestinal disorders
Gingival pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Gastrointestinal disorders
Lower gastrointestinal hemorrhage
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis oral
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
33.3%
1/3 • Number of events 1
|
100.0%
3/3 • Number of events 10
|
71.4%
5/7 • Number of events 13
|
68.4%
91/133 • Number of events 205
|
65.1%
41/63 • Number of events 107
|
|
Gastrointestinal disorders
Oesophagoscopy abnormal
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Gastrointestinal disorders
Rectal mucositis
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
8.3%
11/133 • Number of events 11
|
11.1%
7/63 • Number of events 8
|
|
General disorders
Chest pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
General disorders
Chills
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
General disorders
Death
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
General disorders
Edema limbs
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
General disorders
Fatigue
|
66.7%
2/3 • Number of events 5
|
66.7%
2/3 • Number of events 2
|
42.9%
3/7 • Number of events 4
|
42.1%
56/133 • Number of events 97
|
39.7%
25/63 • Number of events 50
|
|
General disorders
Fever
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
General disorders
Gait abnormal
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
2.3%
3/133 • Number of events 3
|
0.00%
0/63
|
|
General disorders
General symptom
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
General disorders
Ill-defined disorder
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
General disorders
Localized edema
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
General disorders
Pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Hepatobiliary disorders
Gallbladder obstruction
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
Infections and infestations
Conjunctivitis infective
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Infections and infestations
Gingival infection
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
2.3%
3/133 • Number of events 3
|
0.00%
0/63
|
|
Infections and infestations
Infection
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 3
|
3.2%
2/63 • Number of events 2
|
|
Infections and infestations
Mucosal infection
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 3
|
0.00%
0/63
|
|
Infections and infestations
Pneumonia
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Infections and infestations
Skin infection
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Infections and infestations
Tooth infection
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
1.6%
1/63 • Number of events 1
|
|
Infections and infestations
Wound infection
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 3
|
0.00%
0/63
|
|
Injury, poisoning and procedural complications
Arterial injury
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Injury, poisoning and procedural complications
Dermatitis radiation
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
14.3%
1/7 • Number of events 1
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/7
|
4.5%
6/133 • Number of events 6
|
0.00%
0/63
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/7
|
2.3%
3/133 • Number of events 3
|
0.00%
0/63
|
|
Investigations
Bilirubin increased
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
0.00%
0/7
|
0.00%
0/133
|
3.2%
2/63 • Number of events 2
|
|
Investigations
Creatinine increased
|
0.00%
0/3
|
0.00%
0/3
|
28.6%
2/7 • Number of events 5
|
20.3%
27/133 • Number of events 39
|
23.8%
15/63 • Number of events 22
|
|
Investigations
Leukocyte count decreased
|
33.3%
1/3 • Number of events 2
|
66.7%
2/3 • Number of events 5
|
71.4%
5/7 • Number of events 13
|
50.4%
67/133 • Number of events 159
|
54.0%
34/63 • Number of events 149
|
|
Investigations
Lymphocyte count decreased
|
66.7%
2/3 • Number of events 10
|
100.0%
3/3 • Number of events 14
|
100.0%
7/7 • Number of events 32
|
62.4%
83/133 • Number of events 217
|
73.0%
46/63 • Number of events 236
|
|
Investigations
Neutrophil count decreased
|
33.3%
1/3 • Number of events 1
|
66.7%
2/3 • Number of events 5
|
14.3%
1/7 • Number of events 4
|
35.3%
47/133 • Number of events 96
|
28.6%
18/63 • Number of events 53
|
|
Investigations
Platelet count decreased
|
66.7%
2/3 • Number of events 7
|
66.7%
2/3 • Number of events 4
|
85.7%
6/7 • Number of events 19
|
60.2%
80/133 • Number of events 211
|
65.1%
41/63 • Number of events 131
|
|
Investigations
Weight gain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
2.3%
3/133 • Number of events 5
|
0.00%
0/63
|
|
Investigations
Weight loss
|
0.00%
0/3
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
4.5%
6/133 • Number of events 9
|
6.3%
4/63 • Number of events 11
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/3
|
0.00%
0/3
|
28.6%
2/7 • Number of events 2
|
18.0%
24/133 • Number of events 25
|
14.3%
9/63 • Number of events 13
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
0.00%
0/3
|
33.3%
1/3 • Number of events 2
|
14.3%
1/7 • Number of events 1
|
8.3%
11/133 • Number of events 15
|
6.3%
4/63 • Number of events 4
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
6.0%
8/133 • Number of events 8
|
6.3%
4/63 • Number of events 4
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
4.5%
6/133 • Number of events 6
|
0.00%
0/63
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
0.00%
0/3
|
0.00%
0/3
|
28.6%
2/7 • Number of events 2
|
3.0%
4/133 • Number of events 4
|
3.2%
2/63 • Number of events 2
|
|
Metabolism and nutrition disorders
Serum phosphate decreased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
Metabolism and nutrition disorders
Serum potassium increased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 3
|
0.00%
0/63
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
2.3%
3/133 • Number of events 5
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
3.2%
2/63 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
0.00%
0/3
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
6.8%
9/133 • Number of events 10
|
6.3%
4/63 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness left-sided
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
0.00%
0/7
|
2.3%
3/133 • Number of events 3
|
3.2%
2/63 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Short stature
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Upper extremity dysfunction
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor flare
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Ataxia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 2
|
0.00%
0/63
|
|
Nervous system disorders
Cognitive disturbance
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 4
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
3.8%
5/133 • Number of events 5
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Headache
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
15.8%
21/133 • Number of events 33
|
12.7%
8/63 • Number of events 14
|
|
Nervous system disorders
Intracranial hemorrhage
|
33.3%
1/3 • Number of events 2
|
0.00%
0/3
|
14.3%
1/7 • Number of events 2
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
3.8%
5/133 • Number of events 9
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Neurological disorder NOS
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Nystagmus
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 2
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 3
|
0.00%
0/63
|
|
Nervous system disorders
Pyramidal tract syndrome
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Seizure
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.75%
1/133 • Number of events 1
|
6.3%
4/63 • Number of events 4
|
|
Nervous system disorders
Sinus pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.00%
0/133
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Speech disorder
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/7
|
3.8%
5/133 • Number of events 5
|
0.00%
0/63
|
|
Nervous system disorders
Syncope
|
0.00%
0/3
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/133
|
3.2%
2/63 • Number of events 2
|
|
Nervous system disorders
Taste alteration
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
8.3%
11/133 • Number of events 15
|
6.3%
4/63 • Number of events 4
|
|
Nervous system disorders
Tremor
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
3.2%
2/63 • Number of events 2
|
|
Nervous system disorders
Trigeminal nerve disorder
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Psychiatric disorders
Confusion
|
0.00%
0/3
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
1.5%
2/133 • Number of events 3
|
3.2%
2/63 • Number of events 2
|
|
Psychiatric disorders
Depression
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
0.00%
0/7
|
3.8%
5/133 • Number of events 6
|
3.2%
2/63 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
1.6%
1/63 • Number of events 1
|
|
Psychiatric disorders
Personality change
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Renal and urinary disorders
Urinary frequency
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 2
|
0.00%
0/63
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 2
|
1.6%
1/63 • Number of events 2
|
|
Reproductive system and breast disorders
Vaginal dryness
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
100.0%
3/3 • Number of events 3
|
33.3%
1/3 • Number of events 1
|
28.6%
2/7 • Number of events 4
|
33.1%
44/133 • Number of events 89
|
23.8%
15/63 • Number of events 28
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
14.3%
1/7 • Number of events 2
|
24.8%
33/133 • Number of events 68
|
15.9%
10/63 • Number of events 23
|
|
Respiratory, thoracic and mediastinal disorders
Hiccough
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
0.00%
0/7
|
0.00%
0/133
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal examination abnormal
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
6.0%
8/133 • Number of events 12
|
3.2%
2/63 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 2
|
0.00%
0/63
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
66.7%
2/3 • Number of events 2
|
33.3%
1/3 • Number of events 2
|
42.9%
3/7 • Number of events 5
|
38.3%
51/133 • Number of events 96
|
30.2%
19/63 • Number of events 37
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Vascular disorders
Flushing
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
0.00%
0/63
|
|
Vascular disorders
Hypertension
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
1.5%
2/133 • Number of events 3
|
4.8%
3/63 • Number of events 8
|
|
Vascular disorders
Hypotension
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
0.75%
1/133 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/7
|
3.0%
4/133 • Number of events 5
|
3.2%
2/63 • Number of events 3
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place