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

Alternate Title

Carmustine Plus O(6)-benzylguanine in Treating Patients With Recurrent or Progressive Gliomas of the Brain

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	DUMC-1094-99-6R5 DUMC-929-97-6R3, DUMC-980-98-6R4, NCI-T94-0080, NCT00003348, T94-0080

Objectives

I. Determine the maximum tolerated dose of carmustine when administered 
following O6-benzylguanine in patients with recurrent, persistent, or 
progressive cerebral anaplastic gliomas.

II. Characterize the toxic effects associated with this treatment regimen in 
these patients.

III. Observe patients for clinical antitumor response when treated with this 
regimen.

Entry Criteria

Disease Characteristics:

Histologically proven recurrent, persistent, or progressive glioblastoma
multiforme or anaplastic astrocytoma diagnosed by biopsy/resection 

Evaluable residual disease by MRI or CT scan

Prior/Concurrent Therapy:

Biologic therapy:
 Not specified

Chemotherapy:
 At least 4 weeks since prior chemotherapy (6 weeks since prior nitrosourea,
  procarbazine, or mitomycin) and recovered

Endocrine therapy:
 Concurrent corticosteroid therapy must be stable for at least 1 week prior to
  study, if clinically possible  

Radiotherapy:
 At least 4 weeks since prior radiotherapy and recovered

Surgery:
  Not specified

Patient Characteristics:

Age:
 18 and over
  
Performance status:
 Karnofsky 60-100%

Life expectancy:
 Not specified
  
Hematopoietic:
 Absolute granulocyte count at least 1,500/mm3
 Platelet count at least 100,000/mm3  

Hepatic:
 SGOT no greater than 2.5 times upper limit of normal 
 Bilirubin within normal limits

Renal:
 Creatinine no greater than 1.5 mg/dL OR
 Creatinine clearance greater than 60 mL/min
 BUN no greater than 25 mg/dL

Pulmonary:
 DLCO greater than 80% predicted

Other:
 Not pregnant or nursing 
 Fertile patients must use effective contraceptive method during and for 2
  months after study

Expected Enrollment

A total of 24-56 patients (12-28 per stratum) will be accrued in 12 months.

Outline

Patients are stratified according to prior nitrosourea administration (yes or 
no).  (Prior nitrosoureas stratum closed)

An initial cohort of 3 patients per stratum is treated with intravenous 
O6-benzylguanine followed approximately 1 hour later by intravenous carmustine 
every 6 weeks. Additional cohorts of 3-6 patients are treated with escalating 
doses of carmustine until dose limiting toxicity (DLT) is observed. The 
maximum tolerated dose is defined as the dose at which no more than 1 of 6 
patients experiences DLT.

Courses are repeated every 6 weeks in the absence of disease progression or 
unacceptable toxicity.

Trial Contact Information

Trial Lead Organizations

Duke Comprehensive Cancer Center

Henry Friedman, MD, Protocol chair		Ph: 919-684-5301 Email: fried003@mc.duke.edu

Registry Information
Official Title		Phase I Trial of BCNU Plus O6-Benzylguanine in the Treatment of Patients With Recurrent, Persistent or Progressive Cerebral Anaplastic Gliomas
Trial Start Date		1998-05-14
Registered in ClinicalTrials.gov		NCT00003348
Date Submitted to PDQ		1998-05-26
Information Last Verified		2000-06-01