Trial Outcomes & Findings for O6-Benzylguanine and Temozolomide in Treating Young Patients With Recurrent or Progressive Gliomas or Brain Stem Tumors (NCT NCT00275002)

Last Updated: 2022-02-11

Results Overview

The primary endpoint is to assess the percentage of participants with a sustained objective response (complete response (CR) or partial response (PR)). Response is assessed by magnetic resonance imaging (MRI) per the following criteria: CR - disappearance of tumor and PR - ≥50% reduction in tumor based on the maximal cross-sectional measurements. The response must be sustained for at least 8 weeks, and the date of the confirmed sustained response is the date at which the response was first noted by MRI.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

Week 8, 16, 24, 32, and 40 after starting therapy

Results posted on

2022-02-11

Participant Flow

Participants from PBTC member institutions were enrolled between October 2005 and February 2008.

Participant milestones

Participant milestones
Measure	Recurrent High-Grade Gliomas Participants with recurrent or progressive high-grade gliomas receive 120 mg/m\^2 of O6-Benzylguanine administered as a one-hour intravenous infusion, daily for 5 days. Temozolomide, 75 mg/m\^2 is administered orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course, and courses will be repeated every 4 weeks.	Recurrent Brain Stem Tumors Participants with recurrent or progressive brain stem tumors receive 120 mg/m\^2 of O6-Benzylguanine administered as a one-hour intravenous infusion, daily for 5 days. Temozolomide, 75 mg/m\^2 is administered orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course, and courses will be repeated every 4 weeks.
Overall Study STARTED	25	16
Overall Study COMPLETED	3	0
Overall Study NOT COMPLETED	22	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Recurrent High-Grade Gliomas Participants with recurrent or progressive high-grade gliomas receive 120 mg/m\^2 of O6-Benzylguanine administered as a one-hour intravenous infusion, daily for 5 days. Temozolomide, 75 mg/m\^2 is administered orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course, and courses will be repeated every 4 weeks.	Recurrent Brain Stem Tumors Participants with recurrent or progressive brain stem tumors receive 120 mg/m\^2 of O6-Benzylguanine administered as a one-hour intravenous infusion, daily for 5 days. Temozolomide, 75 mg/m\^2 is administered orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course, and courses will be repeated every 4 weeks.
Overall Study Death	1	0
Overall Study Disease progression	21	15
Overall Study Adverse Event	0	1

Baseline Characteristics

O6-Benzylguanine and Temozolomide in Treating Young Patients With Recurrent or Progressive Gliomas or Brain Stem Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Recurrent High-Grade Gliomas n=25 Participants Participants with recurrent or progressive high-grade gliomas receive 120 mg/m\^2 of O6-Benzylguanine administered as a one-hour intravenous infusion, daily for 5 days. Temozolomide, 75 mg/m\^2 is administered orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course, and courses will be repeated every 4 weeks.	Recurrent Brain Stem Tumors n=16 Participants Participants with recurrent or progressive brain stem tumors receive 120 mg/m\^2 of O6-Benzylguanine administered as a one-hour intravenous infusion, daily for 5 days. Temozolomide, 75 mg/m\^2 is administered orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course, and courses will be repeated every 4 weeks.	Total n=41 Participants Total of all reporting groups
Age, Categorical <=18 years	23 Participants n=5 Participants	16 Participants n=7 Participants	39 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	13.4 years STANDARD_DEVIATION 5.1 • n=5 Participants	7.8 years STANDARD_DEVIATION 3.9 • n=7 Participants	11.2 years STANDARD_DEVIATION 5.4 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	4 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	16 participants n=7 Participants	41 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 8, 16, 24, 32, and 40 after starting therapy

Population: Participants included in assessing objective response were those who completed two courses of therapy or those who died or experienced progressive disease prior to completing the second course.

Outcome measures

Outcome measures
Measure	Recurrent High-Grade Gliomas n=25 Participants Participants with recurrent or progressive high-grade gliomas receive 120 mg/m\^2 of O6-Benzylguanine administered as a one-hour intravenous infusion, daily for 5 days. Temozolomide, 75 mg/m\^2 is administered orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course, and courses will be repeated every 4 weeks.	Recurrent Brain Stem Tumors n=16 Participants Participants with recurrent or progressive brain stem tumors receive 120 mg/m\^2 of O6-Benzylguanine administered as a one-hour intravenous infusion, daily for 5 days. Temozolomide, 75 mg/m\^2 is administered orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course, and courses will be repeated every 4 weeks.
Percentage of Participants With an Objective Response (Complete Response or Partial Response)	4 Percent of Participants Interval 0.1 to 20.0	0 Percent of Participants Interval 0.0 to 21.0

SECONDARY outcome

Timeframe: From day 1 of therapy up to 49 months

Population: Participants who received at least one day of the treatment regimen were included in the analysis of this objective.

Clinical and laboratory studies to assess adverse events are obtained at least every four weeks (prior to each course) with some laboratory studies obtained every 2 weeks. Adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0). Attribution of each adverse event to the treatment regimen is determined by the participant's attending physician at the enrolling institution and verified by the study chair.

Outcome measures

Outcome measures
Measure	Recurrent High-Grade Gliomas n=25 Participants Participants with recurrent or progressive high-grade gliomas receive 120 mg/m\^2 of O6-Benzylguanine administered as a one-hour intravenous infusion, daily for 5 days. Temozolomide, 75 mg/m\^2 is administered orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course, and courses will be repeated every 4 weeks.	Recurrent Brain Stem Tumors n=16 Participants Participants with recurrent or progressive brain stem tumors receive 120 mg/m\^2 of O6-Benzylguanine administered as a one-hour intravenous infusion, daily for 5 days. Temozolomide, 75 mg/m\^2 is administered orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course, and courses will be repeated every 4 weeks.
Number of Patients With Grade 3 or 4 Adverse Events at Least Possibly Related to the Combination of O6-benzylguanine and Temozolomide	16 Participants	10 Participants

Adverse Events

Recurrent High-Grade Gliomas

Serious events: 15 serious events

Other events: 25 other events

Deaths: 0 deaths

Recurrent Brain Stem Tumors

Serious events: 12 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dana Wallace

Pediatric Brain Tumor Consortium

Phone: 901-595-2617

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Recurrent High-Grade Gliomas n=25 participants at risk Participants with recurrent or progressive high-grade gliomas receive 120 mg/m\^2 of O6-Benzylguanine administered as a one-hour intravenous infusion, daily for 5 days. Temozolomide, 75 mg/m\^2 is administered orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course, and courses will be repeated every 4 weeks.	Recurrent Brain Stem Tumors n=16 participants at risk Participants with recurrent or progressive brain stem tumors receive 120 mg/m\^2 of O6-Benzylguanine administered as a one-hour intravenous infusion, daily for 5 days. Temozolomide, 75 mg/m\^2 is administered orally, 30 minutes following the completion of each infusion of O6-Benzylguanine. Four consecutive weeks will constitute one course, and courses will be repeated every 4 weeks.
Respiratory, thoracic and mediastinal disorders Apnea	0.00% 0/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	6.2% 1/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	6.2% 1/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Nervous system disorders Ataxia	4.0% 1/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	0.00% 0/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Investigations Bilirubin	4.0% 1/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	0.00% 0/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Infections and infestations Colitis, infectious	4.0% 1/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	6.2% 1/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Gastrointestinal disorders Diarrhea	4.0% 1/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	0.00% 0/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Blood and lymphatic system disorders Febrile neutropenia	4.0% 1/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	0.00% 0/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Nervous system disorders Hydrocephalus	0.00% 0/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	6.2% 1/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Vascular disorders Hypotension	0.00% 0/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	6.2% 1/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	12.5% 2/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Investigations Leukocytes (total WBC)	8.0% 2/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	18.8% 3/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Investigations Lipase	4.0% 1/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	0.00% 0/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Investigations Lymphopenia	0.00% 0/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	18.8% 3/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	6.2% 1/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Nervous system disorders Mental Status	4.0% 1/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	0.00% 0/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Gastrointestinal disorders Nausea	4.0% 1/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	0.00% 0/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Investigations Neutrophils/granulocytes	24.0% 6/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	31.2% 5/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Vascular disorders Phlebitis	0.00% 0/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	6.2% 1/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Investigations Platelets	4.0% 1/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	0.00% 0/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Nervous system disorders Seizure	4.0% 1/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	0.00% 0/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Metabolism and nutrition disorders Hyponatremia	4.0% 1/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	0.00% 0/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.
Nervous system disorders Somnolence	8.0% 2/25 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.	0.00% 0/16 • Adverse events (AEs) were collected from day 1 of starting treatment until 30 days after ceasing treatment (off study). AEs possibly, probably, or definitely attributed to the study drug that occur after the patient is off the study are also collected.