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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00002971
First received: November 1, 1999
Last updated: December 13, 2008
Last verified: March 2003
  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 1

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

Resource links provided by NLM:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Study Chair: Michael Prados, MD UCSF Medical Center at Parnassus
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00002971     History of Changes
Other Study ID Numbers: CDR0000065479, NABTC-9702, NCI-T96-0103
Study First Received: November 1, 1999
Last Updated: December 13, 2008
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

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
O(6)-benzylguanine
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014