Chemotherapy in Treating Patients With Progressive or Recurrent Brain Tumors

June 20, 2013 updated by: New Approaches to Brain Tumor Therapy Consortium

A Phase I/II Trial Of MGI114 For Treatment Of Patients With Recurrent Malignant Gliomas

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 irofulven in treating patients who have progressive or recurrent astrocytoma, oligodendroglioma, or glioblastoma multiforme.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose (MTD) of irofulven alone or combined with anticonvulsants known to be metabolized by cytochrome P450 in patients with progressive or recurrent high-grade anaplastic astrocytoma, anaplastic oligodendroglioma, or glioblastoma multiforme.
  • Assess the pharmacokinetics of this drug on this schedule and determine the effects of P450-inducing anticonvulsants on the pharmacokinetics in these patients.
  • Determine the response rate of patients treated with this drug administered at the MTD.
  • Determine the duration of progression-free survival and overall survival of patients treated with this drug.
  • Determine the toxic effects of this drug in these patients.

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

Patients receive irofulven IV over 30 minutes on days 1-4 or 1-5 (depending on dose-escalation level). Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients (per stratum) receive escalating doses of irofulven until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with irofulven at the recommended phase II dose.

Patients are followed at 1 week and then every 2 months thereafter.

PROJECTED ACCRUAL: Approximately 18 patients (9 per stratum) will be accrued for the phase I portion of the study. Approximately 17-35 patients will be accrued for the phase II portion of the study within 6-12 months.

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

  • United States
    • 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, 27157-1029
        • 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
        • Abramson Cancer Center of the University of Pennsylvania
    • 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 high-grade glioma that is progressive or recurrent after radiotherapy and/or chemotherapy

    • Anaplastic astrocytoma
    • Anaplastic oligodendroglioma
    • Glioblastoma multiforme
  • Prior low-grade glioma that has progressed to high-grade glioma after radiotherapy and/or chemotherapy allowed
  • Measurable disease by MRI or CT scan

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • Transaminases no greater than 2.5 times upper limit of normal

Renal:

  • Creatinine no greater than 1.5 mg/dL

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious concurrent infection or medical illness that would preclude study therapy
  • No other prior malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
  • Mini mental score at least 15

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • See Disease Characteristics
  • No more than 2 prior chemotherapy regimens
  • At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered

Endocrine therapy:

  • Maintained on a stable corticosteroid regimen for at least 5 days before and during study

Radiotherapy:

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

Surgery:

  • Recovered from prior surgery

Other:

  • No other concurrent investigational agents

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

New Approaches to Brain Tumor Therapy Consortium

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Steven S. Rosenfeld, MD, PhD, University of Alabama at Birmingham

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, 2001

Study Completion (Actual)

October 1, 2003

Study Registration Dates

First Submitted

March 3, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

June 24, 2013

Last Update Submitted That Met QC Criteria

June 20, 2013

Last Verified

September 1, 2003

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000068474
  • NABTT-2005
  • JHOC-NABTT-2005

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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