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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00002971

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

138.4

Actual Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: O6-benzylguanine	Phase 1

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Phase I Trial of Pre-Surgical O6-Benzylguanine in the Treatment of Patients With Malignant Glioma

Actual Study Start Date :

Jun 19, 1997

Actual Primary Completion Date :

Feb 20, 2003

Actual Study Completion Date :

Jan 1, 2009

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
2	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94143-0128
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
5	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15213-3489
6	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75235-9154
7	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
8	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
9	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164