Procarbazine in Treating Patients With Recurrent Brain Tumor

A Phase I/II Study of Oral Procarbazine in the Treatment of Recurrent High Grade Astrocytomas

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I/II trial to study the effectiveness of procarbazine in treating patients who have progressive or recurrent astrocytoma, oligodendroglioma, or glioblastoma multiforme following treatment with radiation therapy.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose of oral procarbazine when administered to patients with recurrent glioma receiving or not receiving anticonvulsants metabolized by the P450 hepatic enzyme complex.
  • Determine the pharmacokinetics of oral procarbazine, including any effects of hepatic enzyme inducing drugs, in these patients.
  • Assess the response rate to procarbazine in these patients.
  • Evaluate this regimen in terms of overall survival and duration of disease free survival in these patients.
  • Evaluate the toxicity of this regimen in these patients.

OUTLINE: Phase I of this study is a dose escalation study. Patients are stratified according to concurrent use of anticonvulsant drugs that induce cytochrome P450 (yes vs no drugs or modest-induction drugs).

  • Phase I: Patients receive oral procarbazine once daily for 5 days. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of oral procarbazine until the maximum tolerated dose (MTD) is determined.

  • Phase II: Once the MTD is determined, patients receive procarbazine as in Phase I.

Patients are followed every 2 months until death.

PROJECTED ACCRUAL: A total of 24-35 patients will be accrued for this study.

Study Type

Interventional

Phase

  • Phase 2
  • 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

    • Alabama
      • Birmingham, Alabama, United States, 35294-3300
        • University of Alabama at Birmingham Comprehensive Cancer Center
    • Florida
      • Tampa, Florida, United States, 33612-9497
        • H. Lee Moffitt Cancer Center and Research Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital - Atlanta
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157-1082
        • Comprehensive Cancer Center at Wake Forest University
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4283
        • University of Pennsylvania Cancer Center
    • Texas
      • San Antonio, Texas, United States, 78284-7811
        • University of Texas Health Science Center at San Antonio

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:

  • Histologically proven malignant glioma of one of the following types:

    • Anaplastic astrocytoma
    • Anaplastic oligodendroglioma
    • Glioblastoma multiforme
  • Progressive or recurrent disease after radiotherapy with or without chemotherapy
  • Measurable disease by serial MR or CT

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Greater than 2 months

Hematopoietic:

  • Absolute neutrophil count at least 1500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • SGPT/SGOT no greater than 4 times upper limit of normal

Renal:

  • Creatinine no greater than 1.7 mg/dL

Other:

  • No serious concurrent infection
  • No other illness that would preclude study
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior malignancy within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No concurrent filgrastim (G-CSF) during the first course

Chemotherapy:

  • See Disease Characteristics
  • No more than 1 prior chemotherapy regimen
  • At least 3 weeks since prior chemotherapy (at least 6 weeks since prior nitrosoureas)
  • No more than 2 prior courses of carmustine or lomustine and no greater than 460 mg/m2 or 220 mg/m2, respectively
  • No prior procarbazine

Endocrine therapy:

  • Not specified

Radiotherapy:

  • See Disease Characteristics
  • At least 3 months since prior radiotherapy

Surgery:

  • Prior surgery allowed

Other:

  • Recovered from toxicity of prior therapy
  • At least 10 days since prior anticonvulsants for patients in Arm II
  • No concurrent investigational agents
  • No concurrent ethanol, ephedrine, isoproterenol, epinephrine, tricyclic antidepressants, paragyliline, narcotic analgesics, antihistamines, phenothiazines, hypotensives, or barbiturates
  • At least 14 days since prior antidepressants (e.g., SSRI and/or MAO inhibitor)
  • Must avoid foods high in tyramine (i.e., dark beer, wine, yogurt, cheese, bananas)

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.

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.

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

July 1, 1999

Study Completion (Actual)

August 1, 2003

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

August 19, 2003

First Posted (Estimate)

August 20, 2003

Study Record Updates

Last Update Posted (Estimate)

June 21, 2013

Last Update Submitted That Met QC Criteria

June 20, 2013

Last Verified

May 1, 2007

More Information

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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