Chemotherapy in Treating Patients With Progressive or Recurrent Brain Tumors

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00012038
• Other study ID #: CDR0000068474
• Secondary ID: NABTT-2005JHOC-N
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 3, 2001
• Last updated: June 20, 2013
• Start date: July 2001
• Est. completion date: October 2003

Study information

• Verified date: September 2003
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: October 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• irofulven

Locations

Country	Name	City	State
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
New Approaches to Brain Tumor Therapy Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,