Official Title: “Phase III Randomized Evaluation of 13-Cis-Retinoic Acid (cRA) Plus Procarbazine Versus Procarbazine Alone in the Treatment of Patients With Recurrent Primary Malignant Gliomas”

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.

Study Type: Interventional

Study Design: Treatment, Randomized

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).

Intervention(s) in this Clinical Trial

• Drug: isotretinoin
• Drug: procarbazine hydrochloride

• 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: M.D. Anderson Cancer Center

Overall Clinical Trial Officials and Contacts

Kurt A. Jaeckle, MD Study Chair M.D. Anderson Cancer Center  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00003564

Study ID Number: CDR0000066630

ClinicalTrials.gov Identifier: NCT00003564

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database