Phase I Study of Presurgical O6-Benzylguanine in the Treatment of Patients With Malignant
Glioma
Protocol IDs: NABTC-9702, NCI-T96-0103
Protocol Type: treatment
Sponsorship: NCI-sponsored, NCI CTEP-approved
Status: Active
Age Range: 18 and over
PROJECTED ACCRUAL:
A minimum of 14 patients will be accrued with about 3 patients per month.
OBJECTIVES:
I. Define the dose of O6-benzylguanine (O6-BG) that produces total depletion
of tumor O6-alkylguanine-DNA alkyltransferase (AGT) levels in more than 90% of
cases of cerebral anaplastic astrocytoma or glioblastoma multiforme.
II. Evaluate the qualitative and quantitative toxicities of O6-BG in this
patient population.
PROTOCOL ENTRY CRITERIA:
--Disease Characteristics--
Must be undergoing a diagnostic/therapeutic craniotomy for biopsy/resection of
recurrent or newly diagnosed (or presumed) cerebral anaplastic astrocytoma or
glioblastoma multiforme
Patients undergoing stereotactic biopsy or partial resectioning are eligible
--Prior/Concurrent Therapy--
No concurrent therapy for any other malignancy
At least 2 weeks since any other investigational drug
Biologic therapy:
Not specified
Chemotherapy:
Must have failed or received no prior treatment with a nitrosourea,
procarbazine, or temozolomide
No prior O6-BG
At least 4 weeks since chemotherapy and recovered from all toxic effects
Endocrine therapy:
Not specified
Radiotherapy:
At least 6 weeks since radiotherapy
No more than 10-20% of bone marrow should have had received radiotherapy
--Patient Characteristics--
Age:
18 and over
Performance status:
SWOG 0-2 OR
Karnofsky 60-100%
Hematopoietic:
WBC at least 3,500/mm3
Absolute neutrophil count at least 1,800/mm3
Platelet count at least 125,000/mm3
Hemoglobin at least 9 g/dL
Hepatic:
Bilirubin less than 1.5 mg/dL
SGOT less than 2 times upper limits of normal
Renal:
Creatinine less than 1.5 mg/dL OR
Creatinine clearance greater than 70 mL/min
Cardiovascular:
No severe cardiac disease such as uncontrolled arrhythmias or conduction
defects
No coronary artery disease
Other:
No other medical illnesses that would compromise patient's ability to
tolerate this therapy such as:
Major problems with edema
Poorly controlled hypertension (greater than 180 mmHg systolic, greater than
110 mmHg diastolic)
Major psychiatric illness
No other malignancy requiring active therapy
Not pregnant or nursing
Adequate contraception required of all fertile patients
PROTOCOL OUTLINE:
This is a dose escalating study in which patients are stratified by disease
status (newly diagnosed vs recurrent disease), prior chemotherapy (yes vs no)
and concurrent anticonvulsants (yes vs no).
A single dose of O6-benzylguanine (06-BG) is administered intravenously to the
first 10 patients over 1 hour, 6 hours prior to surgical intervention. Dosage
escalation and accrual depend on toleration of treatment. If at least 3 of 10
patients have 06-alkylguanine-DNA alkyltransferase (AGT) levels that are
detectable, that dose is escalated and 10 additional patients are treated.
Dose escalation continues until at least 8 of 10 patient have undetectable
enzyme activity. At this point 4 more patients are accrued. If at least 11
of 14 patients at this dose have undetectable AGT levels, then this dose
constitutes the biologic modulatory dose of O6-BG. If there are fewer than 11
of 14 patients with undetectable AGT levels, the accrual continues with 10
patients at a higher dose and so on until at least 11 of 14 patients give
undetectable AGT levels.
Treatment ends short of completion if there is unacceptable toxicity following
O6-BG that delays surgery for more than 24 hours, or if the removal of the
tumor specimen occurs less than 3 hours or more than 9 hours after the
completion of the O6-BG infusion.
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
Michael Del Prados, Chair, Ph: 415-476-2966
North American Brain Tumor Consortium |
