Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

O6-benzylguanine and Carmustine in Treating Children With Refractory CNS Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	21 and under	NCI	POG-9870 NCT00003765, P9870

Objectives

I.   Determine the maximum tolerated dose and the dose limiting toxicity of 
carmustine administered after O6-benzylguanine in children with refractory 
primary CNS tumors.

II.  Determine a safe and tolerable dose of carmustine administered after 
O6-benzylguanine to be used in phase II studies.

III. Determine the pharmacokinetics of O6-benzylguanine and its metabolite, 
O6-benzyl-8-oxoguanine, in these patients.

IV.  Seek preliminary evidence of antitumor activity of this regimen in these 
patients.

V.   Evaluate the acute and chronic toxicities, and describe cumulative 
toxicity, in patients treated with multiple courses of this regimen.

Entry Criteria

Disease Characteristics:

Histologically or cytologically proven CNS tumor that is refractory to
conventional therapy or for which no effective therapy is known
 Histological requirement may be waived for brainstem and optic gliomas 

Stratum 2:  No bone marrow involvement

Prior/Concurrent Therapy:

Biologic therapy:
 At least 7 days since prior biologic therapy or immunotherapy and recovered
 At least 6 months since prior bone marrow transplant (stratum 1 only)
 At least 7 days since prior growth factors
 No concurrent filgrastim (G-CSF) prophylaxis
 Stratum 2:  No prior bone marrow transplantation

Chemotherapy:
 At least 2 weeks since prior myelosuppressive chemotherapy (6 weeks for
  nitrosourea) and recovered
 Stratum 2:  No greater than 2 prior chemotherapy regimens
             No prior nitrosourea therapy

Endocrine therapy:
 If receiving dexamethasone, must be on stable or decreasing dose for at least
  2 weeks prior to study

Radiotherapy:
 At least 2 weeks since prior local palliative radiotherapy (small port)
 At least 6 months since prior substantial bone marrow radiation, total body
  irradiation, hemipelvic radiotherapy, or total abdominal/pelvic/chest or
  mantle/Y ports radiotherapy
 Recovered from prior radiotherapy
 Stratum 2:  No prior central axis radiation

Surgery:
 Not specified

Other:
 No other concurrent anticancer or investigational agents

Patient Characteristics:

Age:
 21 and under

Performance status:
 Karnofsky 50-100% OR
 Lansky 50-100%

Life expectancy:
 At least 8 weeks

Hematopoietic:
 Absolute neutrophil count at least 1500/mm3
 Platelet count at least 100,000/mm3 (stratum 2:  at least 125,000/mm3)
 Hemoglobin at least 8 g/dL

Hepatic:
 Bilirubin less than 1.5 mg/dL
 SGOT/SGPT no greater than 2.5 times normal

Renal:
 Creatinine or GFR normal for age

Pulmonary:
 If required, DLCO must be 80% of normal and patient old enough to cooperate
  for DLCO test

Other:
 Neurologic deficits must be stable for at least 2 weeks prior to study
 Not pregnant or nursing
 Negative pregnancy test
 Fertile patients must use effective contraception during and for 6 months
  after study

Expected Enrollment

Approximately 3-36 patients will be accrued for this study within 3 years.

Outline

This is a dose escalation study of carmustine.

Patients receive O6-benzylguanine IV over 1 hour, then, 1 hour later, 
carmustine IV is administered over 1 hour.  Treatment is repeated every 6 
weeks for up to 1 year in the absence of disease progression or unacceptable 
toxicity.

Cohorts of 3-6 patients each receive escalating doses of carmustine until the 
maximum tolerated dose (MTD) is reached.  The MTD is defined as the dose level 
at which fewer than 2 of 6 patients experience dose limiting toxicity (DLT).

If myelosuppression is the DLT, stratum 1 is closed and patients are accrued 
to stratum 2.  If neutropenia is the DLT in stratum 2, patients receive 
filgrastim (G-CSF) subcutaneously beginning on day 2 and continuing until 
blood counts recover.

Patients are followed every 6 months for 4 years, then annually thereafter.

Adams DM, Zhou T, Berg SL, et al.: Phase 1 trial of O6-benzylguanine and BCNU in children with CNS tumors: a Children's Oncology Group study. Pediatr Blood Cancer 50 (3): 549-53, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Pediatric Oncology Group

Denise Adams, MD, Protocol chair(Contact information may not be current)		Ph: 802-656-4414

Registry Information
Official Title		A Trial of 06-BG and BCNU in Children with CNS Tumors
Trial Start Date		1999-05-03
Registered in ClinicalTrials.gov		NCT00003765
Date Submitted to PDQ		1999-01-29
Information Last Verified		2007-10-29
NCI Grant/Contract Number		U10-CA30969