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

NCT ID: NCT00002971

Last Updated: 2018-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-06-19
• Study Completion Date: 2009-01-01

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of O(6)-benzylguanine given before surgery to patients who have malignant glioma.

Detailed Description

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Primary Study Purpose: TREATMENT

Interventions

O6-benzylguanine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Prados, MD

Role: STUDY_CHAIR

UCSF Medical Center at Parnassus

Locations

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Simmons Cancer Center - Dallas

Dallas, Texas, United States

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

CDR0000065479

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-T96-0103

Identifier Type: -

Identifier Source: secondary_id

NABTC-9702

Identifier Type: -

Identifier Source: org_study_id