Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Procarbazine and Isotretinoin in Treating Patients With Recurrent Primary Malignant Gliomas

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	16 and over	NCI	MDA-DM-97050 NCI-T97-0078, NCT00003564, T97-0078

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.

Entry 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

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

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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Kurt Jaeckle, MD, Protocol chair(Contact information may not be current)		Ph: 713-792-8288; 800-392-1611 Email: jaeckle@notes.mdacc.tmc.edu

Registry Information
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
Registered in ClinicalTrials.gov		NCT00003564
Date Submitted to PDQ		1998-09-03
Information Last Verified		2007-05-21