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

Sponsors and Collaborators:	North American Brain Tumor Consortium National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002971

Purpose

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	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: O6-benzylguanine	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: O(6)-Benzylguanine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Trial of Pre-Surgical O6-Benzylguanine in the Treatment of Patients With Malignant Glioma

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

April 1997

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002971

Locations

United States, California
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, United States, 94143-0128
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0752
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15213-3489
United States, Texas
Simmons Cancer Center - Dallas
Dallas, Texas, United States, 75235-9154
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-7811
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164

Sponsors and Collaborators

North American Brain Tumor Consortium

National Cancer Institute (NCI)

Investigators

Study Chair:

Michael Prados, MD

UCSF Medical Center at Parnassus

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000065479, NABTC-9702, NCI-T96-0103
Study First Received:	November 1, 1999
Last Updated:	December 13, 2008
ClinicalTrials.gov Identifier:	NCT00002971
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult brain tumor
adult glioblastoma
adult anaplastic astrocytoma
adult giant cell glioblastoma
adult gliosarcoma

Study placed in the following topic categories:

Glioblastoma
Astrocytoma
Central Nervous System Neoplasms
Recurrence
Brain Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neuroepithelioma
O(6)-benzylguanine
Glioma
Gliosarcoma
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Neoplasms, Nerve Tissue
Nervous System Diseases
Enzyme Inhibitors
Neoplasms, Neuroepithelial
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009