Temozolomide and O6-benzylguanine in Treating Patients With Newly Diagnosed, Recurrent, or Progressive Anaplastic Glioma

June 19, 2013 updated by: Duke University

Phase I Trial of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) in the Treatment of Patients With Newly Diagnosed (Part 1) or Recurrent/Progressive (Parts 1 and 2) Cerebral Anaplastic Gliomas

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining temozolomide and O6-benzylguanine in treating patients who have newly diagnosed, recurrent, or progressive anaplastic glioma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the dose of O6-benzylguanine (O6-BG) effective in producing complete suppression of tumor O6-alkylguanine-DNA alkyltransferase activity in patients with newly diagnosed (closed to accrual 12/19/2000) or recurrent or progressive cerebral anaplastic glioma.
  • Determine the maximum tolerated dose of temozolomide administered after O6-BG in these patients.
  • Determine the toxicity of this regimen in these patients.
  • Determine the anti-tumor response in patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study.

  • Part I: Patients receive escalating doses of O6-benzylguanine (O6-BG) IV continuously for 49 hours until the dose that produces the target depletion of tumor O6-alkylguanine-DNA alkyltransferase (AGT) is determined. Patients undergo a craniotomy after completion of the O6-BG infusion. (closed to accrual 12/19/2000)
  • Part II: After determination of the O6-BG dose in Part I, patients with recurrent malignant gliomas receive O6-BG IV continuously for 49 hours beginning on day 1. Patients also receive oral temozolomide on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experiences dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 20-30 patients (with 14 patients participating in Part II) will be accrued for this study.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Part I:

    • Histologically confirmed, newly diagnosed glioblastoma multiforme or anaplastic astrocytoma (closed to accrual 12/19/2000)

  • Parts I and II:

    • Histologically confirmed astrocytic, oligodendroglial, or mixed glial tumor

      • Grade III or higher
      • Recurrent or progressive after radiotherapy
  • Evaluable residual disease by contrast-enhanced MRI or CT scan

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • Granulocyte count at least 1,500/mm3
  • Platelet count at least 100,000/mm3

Hepatic:

  • SGOT no greater than 2.5 times upper limit of normal
  • Bilirubin normal

Renal:

  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance greater than 60 mL/min
  • BUN no greater than 25 mg/dL

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 6 weeks since prior biologic therapy and recovered

Chemotherapy:

  • At least 2 weeks since prior chemotherapy (including but not limited to topotecan) and recovered

    • Patients in trials with one of the following treatment combinations are allowed to enroll 6 weeks after receiving carmustine (BCNU):

      • BCNU on day 1
      • BCNU on day 1 and topotecan on days 1, 8, 15, 22, 29, and 36
      • BCNU on day 1 and irinotecan on days 1, 8, 15, and 22

Endocrine therapy:

  • Patients on corticosteroids must be on a stable dose for at least 2 weeks before study
  • At least 6 weeks since other prior endocrine therapy and recovered

Radiotherapy:

  • See Disease Characteristics
  • At least 6 weeks since prior radiotherapy and recovered

Surgery:

  • Not specified

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2001

Primary Completion (ACTUAL)

August 1, 2004

Study Completion (ACTUAL)

August 1, 2004

Study Registration Dates

First Submitted

November 6, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (ESTIMATE)

January 27, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

June 20, 2013

Last Update Submitted That Met QC Criteria

June 19, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1388
  • DUMC-1388-02-8R2
  • DUMC-1388-00-8
  • NCI-490
  • DUMC-1388-01-8R1
  • CDR0000068301 (OTHER: DUMC)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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