Phase I Study of Carmustine Plus O6-Benzylguanine in Patients with Recurrent, Persistent, or
Progressive Cerebral Anaplastic Gliomas
Protocol IDs: DUMC-980-98-6R4, NCI-T94-0080, DUMC-929-97-6R3
Protocol Type: treatment
Sponsorship: NCI-sponsored, NCI CTEP-approved
Status: Active
Age Range: 18 and over
PROJECTED ACCRUAL:
A total of 24-56 patients (12-28 per stratum) will be accrued in 12 months.
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.
PROTOCOL 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
PROTOCOL OUTLINE:
Patients are stratified according to prior nitrosourea administration (yes or
no).
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.
WARNING:
The purpose of most clinical trials listed in this database is to test new
cancer treatments, or new methods of diagnosing, screening for or preventing
cancer. Because all potentially harmful side effects are not known before a
trial is conducted, dose and schedule modifications may be required for
participants if they develop side effects from the treatment or test. The
therapy or test described in this clinical trial is intended for use by
clinical oncologists in carefully structured settings, and may not prove to be
more effective than standard treatment. A responsible investigator associated
with this clinical trial should be consulted before using this protocol.
PARTICIPATING ORGANIZATIONS/INVESTIGATORS
Henry S. Friedman, Chair, Ph: 919-684-5301
Duke Comprehensive Cancer Center |
