A Phase I Trial of Pre-Surgical O6-Benzylguanine in the Treatment of Patients With Malignant Glioma
O6-benzylguanine
Brain Diseases+15
+ Central Nervous System Diseases
+ Glioma
Treatment Study
Summary
Study start date: June 19, 1997
Actual date on which the first participant was enrolled.OBJECTIVES: Determine the dose of O6-benzylguanine (O6-BG) that produces total depletion of tumor O6-alkylguanine-DNA alkyltransferase (AGT) levels in more than 90% of patients with cerebral anaplastic astrocytoma or glioblastoma multiforme. Determine the qualitative and quantitative toxicities of O6-BG in this patient population. OUTLINE: This is a dose escalation study. Part I: The first cohort of 10 patients receives O6-benzylguanine (O6-BG) IV over 1 hour at dose level 1 beginning 6 hours prior to surgery. If at least 3 of 10 patients in the first cohort have detectable levels of O6-alkylguanine-DNA alkyltransferase (AGT), then a second cohort of 10 patients receives O6-BG as above at dose level 2. Dose escalation continues until at least 8 of 10 patients have undetectable AGT activity. At this point, 4 additional patients are accrued. If at least 11 of 14 patients at this dose level have undetectable levels of AGT, then this dose level constitutes the biologic modulatory dose of O6-BG. If less than 11 of 14 patients have undetectable levels of AGT, then 10 additional patients are treated at a higher dose. If at any time 3 or more patients at a dose level have detectable AGT activity, accrual is stopped at that dose level and patients are treated at the next higher dose level. (Part I closed to accrual effective 7/10/2000) Part II: An additional cohort of 14 patients receives O6-BG at dose level 5 beginning 18 hours prior to surgery. PROJECTED ACCRUAL: Part I of this study closed to accrual effective 7/10/2000. A total of 14 patients will be accrued for part II of this study at a rate of 3 patients per month.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 18 to 120 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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 resection are eligible 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 limit of normal Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance greater than 70 mL/min Cardiovascular: No cardiovascular illnesses that cannot be adequately controlled with appropriate therapy or would increase risk, e.g.: Severe cardiac disease such as uncontrolled arrhythmias or conduction defects Major problems with edema (e.g., residual leg swelling from deep venous thrombosis) Recent coronary artery disease Poorly controlled hypertension (systolic pressure greater than 180 mm Hg, diastolic pressure greater than 110 mm Hg) Other: No other medical illnesses that cannot be adequately controlled with appropriate therapy or would increase risk, e.g.: Major problems with edema (e.g., Cushing's syndrome) Major psychiatric illness No other malignancy requiring active therapy Not pregnant or nursing Fertile patients must us effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Must have failed or received no prior treatment with a nitrosourea, procarbazine, or temozolomide No prior O6-benzylguanine At least 4 weeks since prior chemotherapy and recovered Endocrine therapy: Not specified Radiotherapy: At least 6 weeks since prior radiotherapy No prior radiotherapy to greater than 10-20% of bone marrow Other: No concurrent therapy for any other malignancy At least 2 weeks since other prior investigational drug
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 9 locations
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, United StatesOpen Jonsson Comprehensive Cancer Center, UCLA in Google MapsUCSF Cancer Center and Cancer Research Institute
San Francisco, United StatesDana-Farber Cancer Institute
Boston, United StatesUniversity of Michigan Comprehensive Cancer Center
Ann Arbor, United States