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

Primary Purpose

Brain and Central Nervous System Tumors

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
O6-benzylguanine
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult giant cell glioblastoma, adult gliosarcoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Jonsson Comprehensive Cancer Center, UCLA
  • UCSF Cancer Center and Cancer Research Institute
  • Dana-Farber Cancer Institute
  • University of Michigan Comprehensive Cancer Center
  • University of Pittsburgh Cancer Institute
  • Simmons Cancer Center - Dallas
  • University of Texas - MD Anderson Cancer Center
  • University of Texas Health Science Center at San Antonio
  • University of Wisconsin Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
June 25, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00002971
Brief Title
O(6)-Benzylguanine in Treating Patients With Malignant Glioma
Official Title
A Phase I Trial of Pre-Surgical O6-Benzylguanine in the Treatment of Patients With Malignant Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
June 19, 1997 (Actual)
Primary Completion Date
February 20, 2003 (Actual)
Study Completion Date
January 1, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors
Keywords
recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult giant cell glioblastoma, adult gliosarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
O6-benzylguanine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Prados, MD
Organizational Affiliation
UCSF Medical Center at Parnassus
Official's Role
Study Chair
Facility Information:
Facility Name
Jonsson Comprehensive Cancer Center, UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1781
Country
United States
Facility Name
UCSF Cancer Center and Cancer Research Institute
City
San Francisco
State/Province
California
ZIP/Postal Code
94143-0128
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0752
Country
United States
Facility Name
University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213-3489
Country
United States
Facility Name
Simmons Cancer Center - Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235-9154
Country
United States
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284-7811
Country
United States
Facility Name
University of Wisconsin Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792-6164
Country
United States

12. IPD Sharing Statement

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

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