Procarbazine and Isotretinoin in Treating Patients With Recurrent Primary Malignant Gliomas

NCT ID: NCT00003564

Last Updated: 2012-02-22

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL

Brief Summary

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. It is not yet known whether giving procarbazine alone or with isotretinoin is more effective for recurrent primary malignant glioma.

PURPOSE: Randomized phase III trial to compare the effectiveness of procarbazine alone or with isotretinoin in treating patients with recurrent primary malignant gliomas.

Detailed Description

OBJECTIVES: I. Determine whether the combination of isotretinoin and procarbazine can improve time to progression and survival compared to procarbazine alone in patients with recurrent malignant gliomas. II. Document the toxicity of these two regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to receive procarbazine alone or in combination with isotretinoin. Arm I: Patients receive oral procarbazine once daily on days 1-14 every 28 days. Oral isotretinoin is administered every 12 hours on days 15-28 every 28 days. Patient receive 6 courses of combined therapy, then continue with oral isotretinoin alone on days 15-28 of each 28 day course, until disease progression or unacceptable toxicity. Arm II: Patients receive procarbazine by mouth once daily on days 1-14 followed by 2 weeks of rest. Patients receive a total of 6 courses of treatment in the absence of disease progression and unacceptable toxicity. Patients are followed until death.

PROJECTED ACCRUAL: This study will accrue a total of 194 patients (97 per treatment group).

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (Procarbazine + Isotretinoin)

Arm I: Oral procarbazine once daily on days 1-14 every 28 days, and Oral isotretinoin every 12 hours on days 15-28 every 28 days; 6 courses of combined therapy, then continue oral isotretinoin alone on days 15-28 of each 28 day course.

Group Type: EXPERIMENTAL

Isotretinoin

Intervention Type: DRUG

Oral isotretinoin is administered every 12 hours on days 15-28 every 28 days.

Procarbazine Hydrochloride

Intervention Type: DRUG

Arm I: Oral procarbazine once daily on days 1-14 every 28 days for 6 courses of combined therapy.

Arm II: Oral procarbazine once daily on days 1-14 followed by 2 weeks of rest for a total of 6 courses.

Arm II (Procarbazine Alone)

Arm II: Oral Procarbazine once daily on days 1-14 followed by 2 weeks of rest for a total of 6 courses of treatment.

Group Type: EXPERIMENTAL

Procarbazine Hydrochloride

Intervention Type: DRUG

Arm I: Oral procarbazine once daily on days 1-14 every 28 days for 6 courses of combined therapy.

Arm II: Oral procarbazine once daily on days 1-14 followed by 2 weeks of rest for a total of 6 courses.

Interventions

Isotretinoin

Oral isotretinoin is administered every 12 hours on days 15-28 every 28 days.

Intervention Type: DRUG

Procarbazine Hydrochloride

Arm I: Oral procarbazine once daily on days 1-14 every 28 days for 6 courses of combined therapy.

Arm II: Oral procarbazine once daily on days 1-14 followed by 2 weeks of rest for a total of 6 courses.

Intervention Type: DRUG

Other Intervention Names

Accutane; 13-cis-retinoic acid

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically proven primary malignant gliomas including the following: Glioblastoma multiforme Gliosarcoma Anaplastic astrocytoma Anaplastic oligodendroglioma Anaplastic infiltrating glioma Mixed malignant gliomas Must show evidence of tumor recurrence or progression on at least 2 serial enhanced MRI scans Must have measurably enhancing residual disease on MRI or CT scan of brain

PATIENT CHARACTERISTICS: Age: 16 and over Performance status: Karnofsky 60-100% Life expectancy: Greater than 8 weeks Hematopoietic: Absolute granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: SGPT less than 2 times institutional normal Alkaline phosphatase less than 2 times institutional normal Bilirubin less than 1.5 mg/dL Renal: BUN less than 1.5 times institutional normal OR Creatinine less than 1.5 times institutional normal Other: No active infection Not pregnant or nursing Fertile patients must use effective contraception 1 month before, during, and 1 month after study No other disease that will obscure toxicity or alter drug metabolism No other concurrent medical illness

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior procarbazine No prior isotretinoin At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered Endocrine therapy: Not specified Radiotherapy: Prior radiotherapy allowed Surgery: Not specified Other: No concurrent tetracyclines

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kurt A. Jaeckle, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Related Links

http://www.mdanderson.org

UT MD Anderson Cancer Center Website

Other Identifiers

P30CA016672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MDA-DM-97050

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-T97-0078

Identifier Type: -

Identifier Source: secondary_id

CDR0000066630

Identifier Type: REGISTRY

Identifier Source: secondary_id

DM97-050

Identifier Type: -

Identifier Source: org_study_id