Trial Outcomes & Findings for Observation or Radiation Therapy and/or Chemotherapy and Second Surgery in Treating Children Who Have Undergone Surgery for Ependymoma (NCT NCT00027846)

Last Updated: 2019-08-07

Results Overview

Event-free survival is calculated from the date of study enrollment to the date of disease progression, disease relapse, occurrence of second neoplasm, or death from any cause. The product-limit (Kaplan-Meier) estimate is for estimation of Event -free survival (EFS) probability at 5 years.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

378 participants

Primary outcome timeframe

Up to 5 years after completion of study treatment

Results posted on

2019-08-07

Participant Flow

Participant milestones

Participant milestones
Measure	GTR1 Differentiated Histology Supratentorial (Group 1) Patients undergo observation.	Radiation (Group 2) Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks	Sub-Total Resection Any Histology or Location (STR) (Group 3) Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC \>1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient
Overall Study STARTED	13	287	78
Overall Study COMPLETED	11	219	41
Overall Study NOT COMPLETED	2	68	37

Reasons for withdrawal

Reasons for withdrawal
Measure	GTR1 Differentiated Histology Supratentorial (Group 1) Patients undergo observation.	Radiation (Group 2) Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks	Sub-Total Resection Any Histology or Location (STR) (Group 3) Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC \>1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient
Overall Study Lost to Follow-up	0	41	9
Overall Study Withdrawal by Subject	0	14	7
Overall Study Ineligible for study	2	6	14
Overall Study Entry into another COG therapeutic study	0	5	2
Overall Study Neuraxis dissemination during/after ther	0	2	5

Baseline Characteristics

Observation or Radiation Therapy and/or Chemotherapy and Second Surgery in Treating Children Who Have Undergone Surgery for Ependymoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GTR1 Differentiated Histology Supratentorial (Group 1) n=13 Participants Patients undergo observation.	Radiation (Group 2) n=287 Participants Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks	Sub-Total Resection Any Histology or Location (STR) (Group 3) n=78 Participants Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC \>1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient	Total n=378 Participants Total of all reporting groups
Age, Categorical <=18 years	13 Participants n=5 Participants	281 Participants n=7 Participants	76 Participants n=5 Participants	370 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 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
Age, Continuous	10.78 years n=5 Participants	5.58 years n=7 Participants	5.18 years n=5 Participants	5.60 years n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	114 Participants n=7 Participants	38 Participants n=5 Participants	159 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	173 Participants n=7 Participants	40 Participants n=5 Participants	219 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	36 Participants n=7 Participants	16 Participants n=5 Participants	52 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	242 Participants n=7 Participants	59 Participants n=5 Participants	311 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	9 Participants n=7 Participants	3 Participants n=5 Participants	15 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	15 Participants n=7 Participants	6 Participants n=5 Participants	21 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	34 Participants n=7 Participants	4 Participants n=5 Participants	39 Participants n=4 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	219 Participants n=7 Participants	62 Participants n=5 Participants	290 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	14 Participants n=7 Participants	5 Participants n=5 Participants	22 Participants n=4 Participants
Region of Enrollment Canada	1 participants n=5 Participants	28 participants n=7 Participants	8 participants n=5 Participants	37 participants n=4 Participants
Region of Enrollment Netherlands	0 participants n=5 Participants	6 participants n=7 Participants	3 participants n=5 Participants	9 participants n=4 Participants
Region of Enrollment United States	12 participants n=5 Participants	243 participants n=7 Participants	62 participants n=5 Participants	317 participants n=4 Participants
Region of Enrollment Australia	0 participants n=5 Participants	10 participants n=7 Participants	5 participants n=5 Participants	15 participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 5 years after completion of study treatment

Population: The product-limit (Kaplan-Meier) estimate is for estimation of event-free survival probability at 5 years. All eligible patients in the study were included.

Outcome measures

Outcome measures
Measure	GTR1 Differentiated Histology Supratentorial (Group 1) n=11 Participants Patients undergo observation.	Radiation (Group 2) n=281 Participants Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks	Sub-Total Resection Any Histology or Location (STR) (Group 3) n=64 Participants Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC \>1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient
Event-free Survival	0.614 Probability of EFS at 5 years Interval 0.33 to 0.9	0.685 Probability of EFS at 5 years Interval 0.63 to 0.74	0.372 Probability of EFS at 5 years Interval 0.25 to 0.5

SECONDARY outcome

Timeframe: Up to 5 years after completion of study treatment

Population: All eligible patients in the study were included. The product-limit (Kaplan-Meier) estimate is for estimation of OS probability.

Overall survival (OS) is measured from the date of study enrollment to the date to death. The product-limit (Kaplan-Meier) estimate is for estimation of OS probability at 5 years.

Outcome measures

Outcome measures
Measure	GTR1 Differentiated Histology Supratentorial (Group 1) n=11 Participants Patients undergo observation.	Radiation (Group 2) n=281 Participants Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks	Sub-Total Resection Any Histology or Location (STR) (Group 3) n=64 Participants Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC \>1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient
Overall Survival	1 Probability of OS at 5 years Interval 1.0 to 1.0	0.862 Probability of OS at 5 years Interval 0.82 to 0.91	0.702 Probability of OS at 5 years Interval 0.58 to 0.82

SECONDARY outcome

Timeframe: At the time of second surgery

Population: Of 64 eligible patients in this group, 25 patients after chemotherapy had the second surgery. Of 25 patients with second surgery after chemotherapy, 19 had a Gross-Total or Near-Total resection. 19/25=76%.

The Rate Of Gross-Total or Near-Total Resection With Second Surgery After Chemotherapy Treatment.

Outcome measures

Outcome measures
Measure	GTR1 Differentiated Histology Supratentorial (Group 1) n=25 Participants Patients undergo observation.	Radiation (Group 2) Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks	Sub-Total Resection Any Histology or Location (STR) (Group 3) Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC \>1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient
Rate of Gross-total or Near-total Resection and Second Surgery After Chemotherapy	76 percentage of participants Interval 54.9 to 90.6	—	—

SECONDARY outcome

Timeframe: At 5 years since the time of radiation therapy.

Population: Of 64 eligible patients who had initial subtotal resection, 5 patients were off-therapy prior to radiation therapy, and 4 patients had a disease progression prior to radiation therapy. There were 55 eligible patients included in the analysis. The product-limit (Kaplan-Meier) estimate is for estimation of EFS probability.

EFS between centrally reviewed differentiated ependymoma and anaplastic ependymoma for the patients who had sub-total resection initially. The event-free survival (EFS) defined as the date of disease progression, disease relapse, occurrence of a second neoplasm, or death from any cause, measured from the start date of radiation therapy. The product-limit (Kaplan-Meier) estimate is for estimation of EFS probability.

Outcome measures

Outcome measures
Measure	GTR1 Differentiated Histology Supratentorial (Group 1) n=41 Participants Patients undergo observation.	Radiation (Group 2) n=14 Participants Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks	Sub-Total Resection Any Histology or Location (STR) (Group 3) Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC \>1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient
Event-free Survival (EFS)	0.424 Probability of EFS at 5 years Interval 0.27 to 0.58	0.298 Probability of EFS at 5 years Interval 0.05 to 0.54	—

SECONDARY outcome

Timeframe: At 5 years since the time of radiation therapy

Population: Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks.

EFS between centrally reviewed differentiated ependymoma and anaplastic ependymoma for the patients who were treated with radiation therapy only. The event-free survival (EFS) defined as the time to disease progression, disease relapse, occurrence of a second neoplasm, or death from any cause, measured from the start of radiation therapy. The product-limit (Kaplan-Meier) estimate is for estimation of EFS probability at 5 years.

Outcome measures

Outcome measures
Measure	GTR1 Differentiated Histology Supratentorial (Group 1) n=157 Participants Patients undergo observation.	Radiation (Group 2) n=124 Participants Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks	Sub-Total Resection Any Histology or Location (STR) (Group 3) Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC \>1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient
Event-free Survival (EFS)	0.746 Probability of EFS at 5 years Interval 0.68 to 0.82	0.607 Probability of EFS at 5 years Interval 0.51 to 0.7	—

SECONDARY outcome

Timeframe: Up to 5 years after completion of study treatment

Population: All eligible patients in the study were included.

Documented and analyzed qualitatively and quantitatively.

Outcome measures

Outcome measures
Measure	GTR1 Differentiated Histology Supratentorial (Group 1) n=11 Participants Patients undergo observation.	Radiation (Group 2) n=281 Participants Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks	Sub-Total Resection Any Histology or Location (STR) (Group 3) n=64 Participants Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC \>1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient
Local Control and Patterns of Failure Local control	6 Participant	217 Participant	29 Participant
Local Control and Patterns of Failure Pattern of failure local	4 Participant	57 Participant	31 Participant
Local Control and Patterns of Failure Pattern of failure Metastatic	0 Participant	26 Participant	5 Participant
Local Control and Patterns of Failure Pattern of failure local & metastatic	1 Participant	7 Participant	4 Participant

Adverse Events

Radiation (Group 2)

Serious events: 38 serious events

Other events: 52 other events

Deaths: 0 deaths

Sub-Total Resection Any Histology or Location (STR) (Group 3)

Serious events: 55 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 626-447-0064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Must obtain sponsor approval.
Publication restrictions are in place

Restriction type: OTHER

Measure	Radiation (Group 2) n=281 participants at risk Supratentorial Anaplastic Ependymoma (GTR1, GTR2, NTR) and Anaplastic or Differentiated Infratentorial Ependymoma (GTR1, GTR2, NTR) and Supratentorial Differentiated Ependymoma(GTR2, NTR). Patients undergo conformal radiation therapy to the brain once daily 5 days a week for 6-6½ weeks. radiation therapy: Given once daily 5 days a week for 6-6½ weeks	Sub-Total Resection Any Histology or Location (STR) (Group 3) n=64 participants at risk Patients receive initial course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and cyclophosphamide IV over 1 hour on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 3 and continuing until blood counts recover. Patients then receive a second course of chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 1 hour on day 1, and oral etoposide on days 1-21. After completion of chemotherapy, patients are evaluated for second therapeutic conventional surgery. Patients who have unresectable disease undergo conformal radiation therapy. Patients who have resectable disease undergo second surgery followed by conformal radiotherapy. filgrastim: Given IV or SC (5mcg/kg/day) start on Day 3 and continue until ANC \>1500/μl given subcutaneously or intravenously. carboplatin: Given IV (375 mg/m2/day) Day 1 given as an IV infusion over one hour. For patient
Blood and lymphatic system disorders Hemoglobin (Hgb)	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	7.8% 5/64 • Number of events 5 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Investigations Leukocytes (total WBC)	5.7% 16/281 • Number of events 18 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	12.5% 8/64 • Number of events 9 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Investigations Platelets	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	10.9% 7/64 • Number of events 7 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
General disorders Fatigue (lethargy, malaise, asthenia)	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	9.4% 6/64 • Number of events 9 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 109/L)	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	7.8% 5/64 • Number of events 6 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Investigations Weight loss	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	6.2% 4/64 • Number of events 4 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Skin and subcutaneous tissue disorders Alopecia	6.0% 17/281 • Number of events 17 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	0.00% 0/64 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Metabolism and nutrition disorders Anorexia	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	6.2% 4/64 • Number of events 5 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Gastrointestinal disorders Constipation	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	9.4% 6/64 • Number of events 6 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Gastrointestinal disorders Nausea	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	7.8% 5/64 • Number of events 6 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Gastrointestinal disorders Vomiting	6.8% 19/281 • Number of events 19 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	10.9% 7/64 • Number of events 9 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Investigations SGOT (AST)	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	9.4% 6/64 • Number of events 6 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Investigations SGPT (ALT)	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	10.9% 7/64 • Number of events 8 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	7.8% 5/64 • Number of events 5 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	7.8% 5/64 • Number of events 5 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..
Metabolism and nutrition disorders Hyponatremia	0.00% 0/281 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..	6.2% 4/64 • Number of events 5 All eligible patients were considered in the evaluation of adverse events. 281 eligible patients were in the group 2 and 64 eligible patients were in the group 3. GTR1 Differentiated Histology Supratentorial (Group 1) is an observation arm. Adverse events were not collected for the " GTR1 Differential Histology Supratentorial(Group 1)" observation arm..