Chemotherapy in Treating Patients With Progressive or Recurrent Brain Tumors

Sponsor

New Approaches to Brain Tumor Therapy Consortium (Other)

Overall Status

Completed

CT.gov ID

NCT00012038

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Duration (Months)

Study Details

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/II trial to study the effectiveness of irofulven in treating patients who have progressive or recurrent astrocytoma, oligodendroglioma, or glioblastoma multiforme.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: irofulven	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2001

Actual Study Completion Date :

Oct 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama	United States	35294-3300
2	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612-9497
3	Emory University Hospital - Atlanta	Atlanta	Georgia	United States	30322
4	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
5	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
6	Henry Ford Hospital	Detroit	Michigan	United States	48202
7	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1029
8	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
9	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283
10	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811