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

Alternate Title

O(6)-benzylguanine in Treating Patients With Malignant Glioma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	NABTC-9702 NCI-T96-0103, NCT00002971

Objectives

1. 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.
2. Determine the qualitative and quantitative toxicities of O6-BG in this patient population.

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 resection are eligible

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

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

Expected Enrollment

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.

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.

Trial Contact Information

Trial Lead Organizations

North American Brain Tumor Consortium

Michael Prados, MD, Protocol chair		Ph: 415-353-2966 Email: pradosm@neurosurg.ucsf.edu

Registry Information
Official Title		A Phase I Trial of Pre-Surgical O6-Benzylguanine in the Treatment of Patients with Malignant Glioma
Trial Start Date		1997-04-01
Registered in ClinicalTrials.gov		NCT00002971
Date Submitted to PDQ		1997-04-01
Information Last Verified		2003-03-04
NCI Grant/Contract Number		CA62399