Trial Outcomes & Findings for Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas (NCT NCT00042991)
NCT ID: NCT00042991
Last Updated: 2014-05-28
Results Overview
The dose limiting toxicity (DLT) analysis population consists of stratum 1A phase I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (course 1 and 2) or who completed the MTD estimation period without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD based on the tradional 3+3 design, where a dose is considered a safe dose only when 0 out of 3, or at most 1 out of 6 patients has DLTs. When two or more patients in a group of 2 to 6 patients had DLTs, then that dose level was considered to be too toxic.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
69 participants
Primary outcome timeframe
Day 1 of gefitinib therapy to end of week 8
Results posted on
2014-05-28
Participant Flow
Accrual to this study started with the first patient who enrolled on 07/01/2002 and ended with the last patient who enrolled on 05/31/2006. Nine institutions enrolled patients on the study.
There was no randomization to the three strata, which were distinct based on diagnosis and the use of enzyme inducing anti-convulsants (EIACD).
Participant milestones
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
These are patients with newly diagnosed brain stem glioma who were treated at Dose 100 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
These are patients with newly diagnosed brain stem glioma who were treated at Dose 250 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
These are patients with newly diagnosed brain stem glioma who were treated at Dose 375 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum-1B: 100 mg/m^2 of Gefitinib + Radiation
These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 100 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum-1B: 250 mg/m^2 of Gefitinib + Radiation
These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 250 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum-1B: 375 mg/m^2 of Gefitinib + Radiation
These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 375 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum-2: 100 mg/m^2 of Gefitinib + Radiation + EIACD
These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 100 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
43
|
7
|
2
|
3
|
5
|
3
|
|
Overall Study
Phase-I Trial
|
6
|
7
|
7
|
2
|
3
|
5
|
3
|
|
Overall Study
Phase-II Trial
|
0
|
36
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
COMPLETED
|
0
|
3
|
1
|
0
|
0
|
0
|
1
|
|
Overall Study
NOT COMPLETED
|
6
|
40
|
6
|
2
|
3
|
5
|
2
|
Reasons for withdrawal
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
These are patients with newly diagnosed brain stem glioma who were treated at Dose 100 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
These are patients with newly diagnosed brain stem glioma who were treated at Dose 250 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
These are patients with newly diagnosed brain stem glioma who were treated at Dose 375 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum-1B: 100 mg/m^2 of Gefitinib + Radiation
These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 100 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum-1B: 250 mg/m^2 of Gefitinib + Radiation
These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 250 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum-1B: 375 mg/m^2 of Gefitinib + Radiation
These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 375 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum-2: 100 mg/m^2 of Gefitinib + Radiation + EIACD
These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 100 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
4
|
2
|
0
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
7
|
2
|
0
|
1
|
0
|
0
|
|
Overall Study
Disease Progression
|
5
|
29
|
2
|
2
|
1
|
4
|
2
|
|
Overall Study
Alternative Therapy
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Gefitinib and Radiation Therapy in Treating Children With Newly Diagnosed Gliomas
Baseline characteristics by cohort
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=6 Participants
These are patients with newly diagnosed brain stem glioma who were treated at Dose 100 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
n=43 Participants
These are patients with newly diagnosed brain stem glioma who were treated at Dose 250 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
n=7 Participants
These are patients with newly diagnosed brain stem glioma who were treated at Dose 375 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum-1B: 100 mg/m^2 of Gefitinib + Radiation
n=2 Participants
These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 100 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum-1B: 250 mg/m^2 of Gefitinib + Radiation
n=3 Participants
These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 250 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum-1B: 375 mg/m^2 of Gefitinib + Radiation
n=5 Participants
These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and NOT receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 375 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Stratum-2: 100 mg/m^2 of Gefitinib + Radiation + EIACD
n=3 Participants
These are patients with newly diagnosed, incompletely resected supertentorial malignant gliomas and receiving enzyme inducing anticonvulsant drugs (EIACD), who were treated at Dose 100 mg/m\^2 of Gefitinib+Radiation, where Gefitinib was administered orally once daily.
|
Total
n=69 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
6 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
68 Participants
n=24 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=24 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
|
Age, Continuous
|
7.25 years
STANDARD_DEVIATION 2.92 • n=5 Participants
|
8.02 years
STANDARD_DEVIATION 3.87 • n=7 Participants
|
10.07 years
STANDARD_DEVIATION 4.71 • n=5 Participants
|
9.17 years
STANDARD_DEVIATION 8.56 • n=4 Participants
|
15.91 years
STANDARD_DEVIATION 5.61 • n=21 Participants
|
11.69 years
STANDARD_DEVIATION 5.40 • n=8 Participants
|
12.82 years
STANDARD_DEVIATION 2.37 • n=8 Participants
|
9.01 years
STANDARD_DEVIATION 4.47 • n=24 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
40 Participants
n=24 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
29 Participants
n=24 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
43 participants
n=7 Participants
|
7 participants
n=5 Participants
|
2 participants
n=4 Participants
|
3 participants
n=21 Participants
|
5 participants
n=8 Participants
|
3 participants
n=8 Participants
|
69 participants
n=24 Participants
|
PRIMARY outcome
Timeframe: Day 1 of gefitinib therapy to end of week 8Population: This cohort includes only the patients who were enrolled and treated on Gefitinib+Radiation during the Phase I component of the trial, where the safety of Gefitinib was assedded at Dose Levels 100 mg/m\^2, 250 mg/m\^2, and 375 mg/m\^2.
The dose limiting toxicity (DLT) analysis population consists of stratum 1A phase I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (course 1 and 2) or who completed the MTD estimation period without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD based on the tradional 3+3 design, where a dose is considered a safe dose only when 0 out of 3, or at most 1 out of 6 patients has DLTs. When two or more patients in a group of 2 to 6 patients had DLTs, then that dose level was considered to be too toxic.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=6 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
n=7 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
n=7 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy
|
2 Participants
|
0 Participants
|
1 Participants
|
—
|
PRIMARY outcome
Timeframe: Assessed pre-radiation, every 8 weeks for 13 courses of therapy, and then every 12 weeksPopulation: Here, we only report the results for Phase-II trial as this objective was specifically for the Phase-II trial. This cohort includes seven patients who were treated during Phase-I at Dose 250 mg/m\^2 of Gefitinib.
Progression-free survival is defined as the interval from intiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurlogical status) or death for patients who failed or to the last date of follow-up for patients without failure
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=43 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Median Progression-free Survival in Newly Diagnosed Brain Stem Gliomas
|
7.43 Months
Interval 1.25 to 37.95
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Assessed from the start of therapy until three years after initiation of gefitinib therapyOverall survival is defined as the interval from initiation of treatment to death or date of last contact for surviving patients
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=43 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Median Survival in Newly Diagnosed Brain Stem Gliomas
|
12.12 Months
Interval 1.71 to 37.95
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and two weeks post completion of radiationPopulation: Out of 43 patients, 35 patients had brain MRI before the treatment started and at the time of the completion of Radiation therapy. Therefore, this analysis is based on the volumetric data from these 35 patients.
This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. In this particular objective, the study aimed to investigate how radiation+gefitinib affect the tumor volume. Tumor volume is measured using Fluid Attenuated Inversion Recovery (FLAIR) before and after the radiation therapy.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=35 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Change in Tumor Volume Measured on Fluid Attenuated Inversion Recovery (FLAIR) Imaging at Before the Protocol Therapy Started and at Two Weeks After Completion of Radiation
|
-14.03 cc
Interval -48.64 to 30.56
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and two weeks post completion of radiationPopulation: Out of 43 patients, for only 19 patients, enhacing tumor was greater than zero based on brain MRI scans before the treatment started and at the time of the completion of Radiation therapy. Therefore, this analysis is based on the enhancing volumetric data from these 19 patients.
This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response,survival, etc.). Volume enhancing is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=19 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Change From Baseline in Volume Enhancing at Two Weeks After Completion of Radiation
|
0.35 cc
Interval -2.97 to 7.31
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and two weeks post completion of radiationPopulation: Out of 43 patients, 29 patients had diffusion scans before the treatment started and at the time of the completion of Radiation therapy. Therefore, this analysis is based on the volumetric data from these 29 patients.
This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response,survival, etc.). Diffusion ratio is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=29 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation
|
-0.41 Ratio
Interval -1.38 to 0.39
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and two weeks post completion of radiationPopulation: Out of 43 patients, 20 patients had perfusion scans before the treatment started and at the time of the completion of Radiation therapy. Therefore, this analysis is based on the volumetric data from these 20 patients.
This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response,survival, etc.). Perfusion ratio is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=20 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation
|
0.72 Ratio
Interval -11.09 to 4.68
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: BaselinePopulation: Out of 43 patients, only 18 Patients had baseline PET scans. Therefore, this analysis is based on these 18 patients.
This study attempts to characterize neuroimaging parameters from positron emission tomography. For each patient, the axial image through the tumor containing the maximum activity per pixel corresponding to the highest FluoroDeoxyGlucose (FDG) uptake was identified and a region of interest (ROI) was drawn based on the FDG definition of the tumor. The mean pixel values within the tumor ROI were normalized by those for normal gray matter to provide ratios of tumor/gray matter. Each patient has a mean tumor to gray matter ratio value and the median of these values across patients is reported.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=18 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Mean Tumor to Gray Matter Ratio Measured at Baseline
|
0.55 Ratio
Interval 0.38 to 0.83
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: BaselinePopulation: Out of 43 patients, only 18 Patients had baseline PET scans. Therefore, this analysis is based on these 18 patients.
This study attempts to characterize neuroimaging parameters from positron emission tomography. For each patient, the axial image through the tumor containing the maximum activity per pixel corresponding to the highest FluoroDeoxyGlucose (FDG) uptake was identified and a region of interest (ROI) was drawn based on the FDG definition of the tumor. The mean pixel values within the tumor ROI were normalized by those for normal white matter to provide ratios of tumor/gray matter. Each patient has a mean tumor to white matter ratio value and the median of these values across patients is reported.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=18 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Mean Tumor to White Matter Ratio Measured at Baseline
|
1.16 Ratio
Interval 0.92 to 2.53
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 2 of course 1Population: PK Data was combined at each dose level accross strata (Stratum 1A, Stratum 1B, and Stratum 2); at Dose 250 mg/m\^2 of Gefitinib accross strata, PK data from Phase-I patients was analysed earlier for the publication of the Phase-I trial. PK data for the Phase-II patients was analyzed separately for the Phase-II publication.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=18 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
n=6 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
n=8 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
n=8 Participants
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Peak Serum Concentration of Gefitinib (Cmax)
|
1.10 mcg/ml
Interval 0.39 to 1.86
|
0.83 mcg/ml
Interval 0.45 to 1.36
|
0.44 mcg/ml
Interval 0.28 to 0.71
|
1.89 mcg/ml
Interval 0.93 to 2.42
|
SECONDARY outcome
Timeframe: Week 2 of course 1Population: PK Data was combined at each dose level accross strata (Stratum 1A, Stratum 1B, and Stratum 2); at Dose 250 mg/m\^2 of Gefitinib accross strata, PK data from Phase-I patients was analysed earlier for the publication of the Phase-I trial. PK data for the Phase-II patients was analyzed separately for the Phase-II publication.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=18 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
n=6 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
n=8 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
n=8 Participants
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Elimination Half Life of Gefitinib (t1/2)
|
15.2 hour
Interval 9.2 to 24.9
|
17.6 hour
Interval 4.8 to 41.3
|
9.9 hour
Interval 1.8 to 19.9
|
10.4 hour
Interval 3.8 to 39.2
|
SECONDARY outcome
Timeframe: Week 2 of course 1Population: PK Data was combined at each dose level accross strata (Stratum 1A, Stratum 1B, and Stratum 2); at Dose 250 mg/m\^2 of Gefitinib accross strata, PK data from Phase-I patients was analysed earlier for the publication of the Phase-I trial. PK data for the Phase-II patients was analyzed separately for the Phase-II publication.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=18 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
n=6 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
n=8 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
n=8 Participants
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Clearance of Gefitinib (Cl)
|
15.2 L/hr/m2
Interval 9.2 to 24.9
|
20.9 L/hr/m2
Interval 12.6 to 33.9
|
12.8 L/hr/m2
Interval 1.8 to 21.8
|
15.0 L/hr/m2
Interval 5.8 to 25.8
|
SECONDARY outcome
Timeframe: Week 2 of course 1Population: PK Data was combined at each dose level accross strata (Stratum 1A, Stratum 1B, and Stratum 2); at Dose 250 mg/m\^2 of Gefitinib accross strata, PK data from Phase-I patients was analysed earlier for the publication of the Phase-I trial. PK data for the Phase-II patients was analyzed separately for the Phase-II publication.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=18 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
n=6 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
n=8 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
n=8 Participants
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Time of Maximum Clearance of Gefitinib (Tmax)
|
3.2 Hour
Interval 2.0 to 6.5
|
4.2 Hour
Interval 2.0 to 6.0
|
4.9 Hour
Interval 1.2 to 6.2
|
4.2 Hour
Interval 2.3 to 6.4
|
SECONDARY outcome
Timeframe: Week 2 of course 1Population: PK Data was combined at each dose level accross strata (Stratum 1A, Stratum 1B, and Stratum 2); at Dose 250 mg/m\^2 of Gefitinib accross strata, PK data from Phase-I patients was analysed earlier for the publication of the Phase-I trial. PK data for the Phase-II patients was analyzed separately for the Phase-II publication.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=18 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
n=6 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
n=8 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
n=8 Participants
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Gefitinib Area Under the Concentration Curve From 0-24 Hours (AUC)
|
16.4 mcg/L*hr
Interval 10.0 to 27.1
|
11.8 mcg/L*hr
Interval 4.3 to 16.7
|
5.3 mcg/L*hr
Interval 3.7 to 11.8
|
25.3 mcg/L*hr
Interval 18.4 to 35.3
|
SECONDARY outcome
Timeframe: Pre-treatmentPopulation: Epidermal growth factor receptor is only possible with tumor sample, which is only potentially available from supratentorial malignant glioma patients treated on Stratum-1B and Stratum-2. Of 10 Stratum-1B and 3 Stratum-2 patients (n=13), tumor material was available from 11 patients (8 in Stratum-1A and 3 in Stratum-2).
Epidermal growth factor receptor (EFGR) is a protein found on the surface of cells to which epidermal growth factor (EGF) binds. When EGF attaches to EGFR, it activates the enzyme tyrosine kinase, triggering reactions that cause the cells to grow and multiply.
Outcome measures
| Measure |
Stratum 1A-100 mg/m^2 of Gefitinib + Radiation
n=11 Participants
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 100 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-250 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 250 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Stratum 1A-375 mg/m^2 of Gefitinib + Radiation
These are patients with brain stem glioma who were treated during the Phase-I trial of Radiation+Dose 375 mg/m\^2 of Gefitinib, where Gefitinib was administered orally once daily.
|
Dose 375 mg/m^2 of Gefitinib
This cohort includes all Phase-I patients treated at 375 mg/m\^2 of Gefitinib regardless of diagnosis; that is, this group includes both brain stem gliomas and supratentorial malignant gliomas. Eight of 12 patients had adequate PK samples for the PK evaluation.
|
|---|---|---|---|---|
|
Number of Patients With Epidermal Growth Factor Receptor (EGFR) Amplification
|
5 Participants
|
—
|
—
|
—
|
Adverse Events
Stratum IA at Dose 100 mg/m^2
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Stratum IA at Dose 250 mg/m^2
Serious events: 15 serious events
Other events: 43 other events
Deaths: 0 deaths
Stratum IA at Dose 375 mg/m^2
Serious events: 5 serious events
Other events: 7 other events
Deaths: 0 deaths
Stratum IB at Dose 100 mg/m^2
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Stratum IB at Dose 250 mg/m^2
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Stratum IB at Dose 375 mg/m^2
Serious events: 5 serious events
Other events: 5 other events
Deaths: 0 deaths
Stratum II at Dose 100 mg/m^2
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Stratum IA at Dose 100 mg/m^2
n=6 participants at risk
Brain Stem Glioma patients treated at 100 mg/m2
|
Stratum IA at Dose 250 mg/m^2
n=43 participants at risk
Brain Stem Glioma patients treated at 250 mg/m2
|
Stratum IA at Dose 375 mg/m^2
n=7 participants at risk
Brain Stem Glioma patients treated at 375 mg/m2
|
Stratum IB at Dose 100 mg/m^2
n=2 participants at risk
Patients with STMG treated at 100 mg/m2
|
Stratum IB at Dose 250 mg/m^2
n=3 participants at risk
Patients with STMG treated at 250 mg/m2
|
Stratum IB at Dose 375 mg/m^2
n=5 participants at risk
Patients with STMG treated at 375 mg/m2
|
Stratum II at Dose 100 mg/m^2
n=3 participants at risk
Patients with STMG treated at 100 mg/m2 who are receiving EIACD
|
|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Anorexia
|
0.00%
0/6
|
4.7%
2/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Investigations
Bilirubin
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
CNS hemorrhage/bleeding
|
0.00%
0/6
|
7.0%
3/43
|
14.3%
1/7
|
0.00%
0/2
|
33.3%
1/3
|
40.0%
2/5
|
0.00%
0/3
|
|
Psychiatric disorders
Confusion
|
0.00%
0/6
|
0.00%
0/43
|
0.00%
0/7
|
50.0%
1/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
General disorders
Death not associated with CTCAE term (Disease progression NOS )
|
0.00%
0/6
|
9.3%
4/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Dehydration
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Diarrhea patients without colostomy
|
0.00%
0/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
0.00%
0/3
|
|
General disorders
Fatigue (lethargy, malaise, asthenia)
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Headache
|
0.00%
0/6
|
2.3%
1/43
|
28.6%
2/7
|
50.0%
1/2
|
0.00%
0/3
|
60.0%
3/5
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Hemoglobin (Hgb)
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/6
|
4.7%
2/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils (Bladder (urinary) )
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils (Conjunctiva )
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils (Skin (cellulitis) )
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Infections and infestations
Infection with unknown ANC (Brain (encephalitis, infectious) )
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Infections and infestations
Infection without neutropenia
|
0.00%
0/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Lymphopenia
|
16.7%
1/6
|
7.0%
3/43
|
14.3%
1/7
|
0.00%
0/2
|
33.3%
1/3
|
40.0%
2/5
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Neurology - Other
|
0.00%
0/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
33.3%
1/3
|
|
Nervous system disorders
Neuropathy - cranial
|
0.00%
0/6
|
2.3%
1/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Neuropathy - sensory
|
0.00%
0/6
|
2.3%
1/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Neuropathy: cranial (CN IX Motor-pharynx; Sensory-ear, pharynx, tongue )
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Investigations
Neutrophils/granulocytes (ANC/AGC)
|
0.00%
0/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Nervous system disorders
Nystagmus
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Seizure
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
50.0%
1/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Somnolence/depressed level of consciousness
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Speech impairment (e.g., dysphasis or aphasia)
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
50.0%
1/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
50.0%
1/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
General disorders
Weight loss
|
0.00%
0/6
|
4.7%
2/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Uric acid, serum-high (hyperuricemia)
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Neuropathy: motor
|
0.00%
0/6
|
2.3%
1/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Investigations
Fibrinogen
|
16.7%
1/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
Other adverse events
| Measure |
Stratum IA at Dose 100 mg/m^2
n=6 participants at risk
Brain Stem Glioma patients treated at 100 mg/m2
|
Stratum IA at Dose 250 mg/m^2
n=43 participants at risk
Brain Stem Glioma patients treated at 250 mg/m2
|
Stratum IA at Dose 375 mg/m^2
n=7 participants at risk
Brain Stem Glioma patients treated at 375 mg/m2
|
Stratum IB at Dose 100 mg/m^2
n=2 participants at risk
Patients with STMG treated at 100 mg/m2
|
Stratum IB at Dose 250 mg/m^2
n=3 participants at risk
Patients with STMG treated at 250 mg/m2
|
Stratum IB at Dose 375 mg/m^2
n=5 participants at risk
Patients with STMG treated at 375 mg/m2
|
Stratum II at Dose 100 mg/m^2
n=3 participants at risk
Patients with STMG treated at 100 mg/m2 who are receiving EIACD
|
|---|---|---|---|---|---|---|---|
|
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)
|
33.3%
2/6
|
51.2%
22/43
|
28.6%
2/7
|
0.00%
0/2
|
33.3%
1/3
|
20.0%
1/5
|
33.3%
1/3
|
|
Investigations
AST, SGOT(serum glutamic oxaloacetic transaminase)
|
33.3%
2/6
|
30.2%
13/43
|
14.3%
1/7
|
0.00%
0/2
|
33.3%
1/3
|
20.0%
1/5
|
33.3%
1/3
|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
16.7%
1/6
|
34.9%
15/43
|
28.6%
2/7
|
50.0%
1/2
|
33.3%
1/3
|
60.0%
3/5
|
0.00%
0/3
|
|
Investigations
Alkaline phosphatase
|
0.00%
0/6
|
9.3%
4/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
33.3%
1/3
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)
|
66.7%
4/6
|
20.9%
9/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
40.0%
2/5
|
0.00%
0/3
|
|
Investigations
Amylase
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Anorexia
|
50.0%
3/6
|
25.6%
11/43
|
14.3%
1/7
|
50.0%
1/2
|
33.3%
1/3
|
0.00%
0/5
|
33.3%
1/3
|
|
Nervous system disorders
Ataxia (incoordination)
|
50.0%
3/6
|
23.3%
10/43
|
28.6%
2/7
|
50.0%
1/2
|
0.00%
0/3
|
0.00%
0/5
|
33.3%
1/3
|
|
Ear and labyrinth disorders
Auditory/Ear - Other (Specify, __)
|
16.7%
1/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Bicarbonate, serum-low
|
0.00%
0/6
|
11.6%
5/43
|
28.6%
2/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Calcium, serum-high (hypercalcemia)
|
0.00%
0/6
|
7.0%
3/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)
|
33.3%
2/6
|
46.5%
20/43
|
42.9%
3/7
|
0.00%
0/2
|
66.7%
2/3
|
40.0%
2/5
|
33.3%
1/3
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/6
|
7.0%
3/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Cognitive disturbance
|
0.00%
0/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
33.3%
1/3
|
|
Psychiatric disorders
Confusion
|
0.00%
0/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
40.0%
2/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Constipation
|
33.3%
2/6
|
41.9%
18/43
|
28.6%
2/7
|
0.00%
0/2
|
33.3%
1/3
|
20.0%
1/5
|
0.00%
0/3
|
|
General disorders
Constitutional Symptoms - Other (Specify, __)
|
83.3%
5/6
|
9.3%
4/43
|
100.0%
7/7
|
100.0%
2/2
|
100.0%
3/3
|
60.0%
3/5
|
66.7%
2/3
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6
|
32.6%
14/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
40.0%
2/5
|
0.00%
0/3
|
|
Investigations
Creatinine
|
0.00%
0/6
|
7.0%
3/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Endocrine disorders
Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae)
|
66.7%
4/6
|
32.6%
14/43
|
14.3%
1/7
|
0.00%
0/2
|
33.3%
1/3
|
40.0%
2/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Specify, __)
|
0.00%
0/6
|
11.6%
5/43
|
14.3%
1/7
|
0.00%
0/2
|
33.3%
1/3
|
40.0%
2/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
2/6
|
60.5%
26/43
|
28.6%
2/7
|
0.00%
0/2
|
66.7%
2/3
|
0.00%
0/5
|
33.3%
1/3
|
|
Nervous system disorders
Dizziness
|
16.7%
1/6
|
7.0%
3/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Eye disorders
Dry eye syndrome
|
0.00%
0/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
33.3%
1/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Dry mouth/salivary gland (xerostomia)
|
16.7%
1/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
33.3%
2/6
|
39.5%
17/43
|
42.9%
3/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Dysphagia (difficulty swallowing)
|
0.00%
0/6
|
11.6%
5/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
33.3%
2/6
|
11.6%
5/43
|
28.6%
2/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Esophagitis
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
0.00%
0/6
|
51.2%
22/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
16.7%
1/6
|
30.2%
13/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Investigations
Fibrinogen
|
16.7%
1/6
|
7.0%
3/43
|
28.6%
2/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Vascular disorders
Flushing
|
16.7%
1/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Investigations
GGT (gamma-Glutamyl transpeptidase)
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Gastritis (including bile reflux gastritis)
|
16.7%
1/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Gastrointestinal - Other (Specify, __)
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
66.7%
4/6
|
37.2%
16/43
|
57.1%
4/7
|
50.0%
1/2
|
33.3%
1/3
|
80.0%
4/5
|
33.3%
1/3
|
|
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)
|
66.7%
4/6
|
18.6%
8/43
|
28.6%
2/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)
|
16.7%
1/6
|
34.9%
15/43
|
0.00%
0/7
|
0.00%
0/2
|
33.3%
1/3
|
40.0%
2/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Heartburn/dyspepsia
|
16.7%
1/6
|
9.3%
4/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Hemoglobin
|
66.7%
4/6
|
27.9%
12/43
|
57.1%
4/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
33.3%
1/3
|
|
Vascular disorders
Hot flashes/flushes
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Renal and urinary disorders
Incontinence, urinary
|
0.00%
0/6
|
7.0%
3/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Infections and infestations
Infection - Other (Specify, __)
|
83.3%
5/6
|
16.3%
7/43
|
28.6%
2/7
|
0.00%
0/2
|
100.0%
3/3
|
60.0%
3/5
|
33.3%
1/3
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/6
|
9.3%
4/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Eye disorders
Keratitis (corneal inflammation/corneal ulceration)
|
16.7%
1/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Investigations
Leukocytes (total WBC)
|
66.7%
4/6
|
44.2%
19/43
|
42.9%
3/7
|
100.0%
2/2
|
33.3%
1/3
|
40.0%
2/5
|
33.3%
1/3
|
|
Investigations
Lymphopenia
|
83.3%
5/6
|
58.1%
25/43
|
57.1%
4/7
|
0.00%
0/2
|
33.3%
1/3
|
60.0%
3/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Magnesium, serum-high (hypermagnesemia)
|
33.3%
2/6
|
23.3%
10/43
|
14.3%
1/7
|
0.00%
0/2
|
33.3%
1/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Magnesium, serum-low (hypomagnesemia)
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
33.3%
1/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
33.3%
1/3
|
|
Investigations
Metabolic/Laboratory - Other (Specify, __)
|
33.3%
2/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
0.00%
0/6
|
11.6%
5/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Nausea
|
16.7%
1/6
|
39.5%
17/43
|
42.9%
3/7
|
50.0%
1/2
|
33.3%
1/3
|
60.0%
3/5
|
0.00%
0/3
|
|
Nervous system disorders
Neurology - Other (Specify, __)
|
16.7%
1/6
|
11.6%
5/43
|
28.6%
2/7
|
0.00%
0/2
|
33.3%
1/3
|
40.0%
2/5
|
33.3%
1/3
|
|
Nervous system disorders
Neuropathy: motor
|
50.0%
3/6
|
27.9%
12/43
|
57.1%
4/7
|
0.00%
0/2
|
33.3%
1/3
|
0.00%
0/5
|
33.3%
1/3
|
|
Nervous system disorders
Neuropathy: sensory
|
33.3%
2/6
|
7.0%
3/43
|
0.00%
0/7
|
50.0%
1/2
|
0.00%
0/3
|
40.0%
2/5
|
0.00%
0/3
|
|
Investigations
Neutrophils/granulocytes (ANC/AGC)
|
66.7%
4/6
|
18.6%
8/43
|
28.6%
2/7
|
50.0%
1/2
|
33.3%
1/3
|
20.0%
1/5
|
33.3%
1/3
|
|
Nervous system disorders
Nystagmus
|
33.3%
2/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Eye disorders
Ocular surface disease
|
16.7%
1/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Eye disorders
Ocular/Visual - Other (Specify, __)
|
16.7%
1/6
|
7.0%
3/43
|
0.00%
0/7
|
50.0%
1/2
|
33.3%
1/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Eye disorders
Ophthalmoplegia/diplopia (double vision)
|
0.00%
0/6
|
14.0%
6/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Cardiac disorders
Palpitations
|
0.00%
0/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Phosphate, serum-low (hypophosphatemia)
|
16.7%
1/6
|
48.8%
21/43
|
57.1%
4/7
|
50.0%
1/2
|
33.3%
1/3
|
0.00%
0/5
|
33.3%
1/3
|
|
Investigations
Platelets
|
33.3%
2/6
|
14.0%
6/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
40.0%
2/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Potassium, serum-high (hyperkalemia)
|
16.7%
1/6
|
14.0%
6/43
|
14.3%
1/7
|
50.0%
1/2
|
0.00%
0/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)
|
16.7%
1/6
|
46.5%
20/43
|
28.6%
2/7
|
50.0%
1/2
|
0.00%
0/3
|
40.0%
2/5
|
33.3%
1/3
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other (Specify, __)
|
0.00%
0/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
33.3%
1/3
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
66.7%
4/6
|
67.4%
29/43
|
71.4%
5/7
|
0.00%
0/2
|
66.7%
2/3
|
40.0%
2/5
|
33.3%
1/3
|
|
Skin and subcutaneous tissue disorders
Rash: acne/acneiform
|
0.00%
0/6
|
16.3%
7/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Renal and urinary disorders
Renal/Genitourinary - Other (Specify, __)
|
33.3%
2/6
|
11.6%
5/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
33.3%
1/3
|
|
Nervous system disorders
Seizure
|
0.00%
0/6
|
0.00%
0/43
|
0.00%
0/7
|
50.0%
1/2
|
66.7%
2/3
|
0.00%
0/5
|
33.3%
1/3
|
|
Metabolism and nutrition disorders
Sodium, serum-high (hypernatremia)
|
0.00%
0/6
|
23.3%
10/43
|
57.1%
4/7
|
0.00%
0/2
|
33.3%
1/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
0.00%
0/6
|
23.3%
10/43
|
57.1%
4/7
|
0.00%
0/2
|
33.3%
1/3
|
20.0%
1/5
|
0.00%
0/3
|
|
Nervous system disorders
Somnolence/depressed level of consciousness
|
16.7%
1/6
|
0.00%
0/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
20.0%
1/5
|
33.3%
1/3
|
|
Nervous system disorders
Speech impairment (e.g., dysphasia or aphasia)
|
0.00%
0/6
|
11.6%
5/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Nervous system disorders
Taste alteration (dysgeusia)
|
0.00%
0/6
|
11.6%
5/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Triglyceride, serum-high (hypertriglyceridemia)
|
0.00%
0/6
|
0.00%
0/43
|
0.00%
0/7
|
50.0%
1/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Uric acid, serum-high (hyperuricemia)
|
16.7%
1/6
|
14.0%
6/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Renal and urinary disorders
Urinary frequency/urgency
|
0.00%
0/6
|
14.0%
6/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Renal and urinary disorders
Urinary retention (including neurogenic bladder)
|
16.7%
1/6
|
0.00%
0/43
|
14.3%
1/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
|
Gastrointestinal disorders
Vomiting
|
66.7%
4/6
|
74.4%
32/43
|
57.1%
4/7
|
100.0%
2/2
|
66.7%
2/3
|
60.0%
3/5
|
0.00%
0/3
|
|
Investigations
Weight gain
|
0.00%
0/6
|
7.0%
3/43
|
0.00%
0/7
|
0.00%
0/2
|
0.00%
0/3
|
0.00%
0/5
|
0.00%
0/3
|
Additional Information
Mehmet Kocak
Operations and Biostatistics Center for Pediatric Brain Tumor Consortium (PBTC)
Phone: 9015952947
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60