SU-101 Compared With Procarbazine in Treating Patients With Glioblastoma Multiforme

Condition(s) targeted: Brain and Central Nervous System Tumors

Intervention: leflunomide (Drug); procarbazine hydrochloride (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: SUGEN, Incorporated - Redwood City

Official(s) and/or principal investigator(s):
Alison L. Hannah, MBBS, Study Chair, Affiliation: SUGEN, Incorporated - South San Francisco

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether SU-101 is more effective than procarbazine in treating patients with glioblastoma multiforme.

PURPOSE: Randomized phase III trial to compare the effectiveness of SU-101 with that of procarbazine in treating patients with glioblastoma multiforme that has recurred.

Official title: A Phase III Randomized Study of SU101 Versus Procarbazine for Patients With Glioblastoma Multiforme in First Relapse

Study design: Treatment, Randomized

Detailed description: OBJECTIVES: I. Compare the median survival of patients with glioblastoma multiforme in first relapse treated with intravenous leflunomide (SU101) administered as a loading dose with weekly maintenance therapy versus oral, single-agent procarbazine administered daily for 28 days every 56 days. II. Compare the median time to progression for these regimens in these patients. III. Assess the objective response of these patients. IV. Assess the safety of SU101 given on this schedule. V. Describe the health-related quality of life of these patients.

OUTLINE: This is a randomized, open label, multicenter study. Patients are stratified according to performance status (Karnofsky 60-80% vs 90-100%), age (less than 50 vs 50 and over), and time from initial diagnosis to recurrence (6 months or greater vs less than 6 months). Patients are randomized to one of two treatment arms. Arm I: Patients receive leflunomide (SU101) IV over 6 hours daily on days 1-4, again 4-8 days later, and weekly thereafter for a total of 4 loading dose infusions and six maintenance infusions in course 1. Patients receive 7 weekly maintenance infusions of SU101 in courses thereafter. Treatment repeats every 8 weeks. Arm II: Patients receive procarbazine orally once or twice daily for 4 weeks. Treatment is repeated every 8 weeks. All patients complete a health-related quality-of-life questionnaire every 8 weeks and at study withdrawal. Treatment courses continue up to a maximum of 1 year in the absence of unacceptable toxicity or disease progression. Patients are followed every 2 months, beginning 30 days after study completion.

PROJECTED ACCRUAL: A maximum of 380 patients will be accrued for this study.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS: Histologically proven refractory or recurrent supratentorial glioblastoma multiforme Bidimensionally measurable, enhancing residual disease by T1-weighted gadolinium-enhanced MRI required within 15 days prior to treatment Stable dose of corticosteroids required for at least 7 days prior to scan

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 75,000/mm3 Hemoglobin at least 9 g/dL without blood transfusions for 15 days prior to treatment Hepatic: AST/SGOT no greater than 3 times upper limit of normal (ULN) Bilirubin less than 1. 5 times ULN Renal: Creatinine no greater than 2 mg/dL OR Creatinine clearance at least 40 mL/min Other: Not allergic to etoposide Effective contraception required of fertile patients Negative serum pregnancy test required of fertile women No other acute or chronic medical or psychiatric condition

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior leflunomide (SU101) therapy No more than one prior single-agent or combination systemic chemotherapy regimen for initial disease Radiosensitizer(s) concurrent with radiotherapy allowed in addition to chemotherapy for primary disease At least 6 weeks since nitrosourea or mitomycin At least 2 weeks since vincristine No prior single-agent procarbazine At least 4 weeks since other chemotherapy No concurrent chemotherapy agents Endocrine therapy: No concurrent hormone therapy (except medroxyprogesterone acetate for appetite stimulation) Less than 4 weeks of prior hormonal therapy (tamoxifen or retinoids) if failed one prior chemotherapy regimen Radiotherapy: Prior conventional radiotherapy for initial disease required No more than one prior course of radiotherapy At least 8 weeks since radiotherapy No prior interstitial radiotherapy No concurrent radiotherapy Surgery: Maximally feasible resection for initial disease required No more than two resections permitted At least 1 week since surgery and/or biopsy for disease No prior interstitial radiotherapy or implanted BCNU-wafers No concurrent surgery (including resection, stereotactic surgery or interstitial implants) Other: No concurrent investigational agent At least 4 weeks since prior investigational agent At least 1 week since cholestyramine or monoamine oxidase inhibitors

Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada

Arizona Cancer Center, Tucson, Arizona 85724, United States

St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85001-2071, United States

Beckman Research Institute, City of Hope, Los Angeles, California 91010, United States

Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095-1781, United States

St. Francis Hospital, San Francisco, California 94109, United States

USC/Norris Comprehensive Cancer Center, Los Angeles, California 90033-0800, United States

University of Colorado Cancer Center, Denver, Colorado 80262, United States

H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, United States

Mount Sinai Comprehensive Cancer Center, Miami Beach, Florida 33140, United States

Medical College of Georgia Hospital and Clinics, Augusta, Georgia 30912-3620, United States

Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611, United States

Indiana University Cancer Center, Indianapolis, Indiana 46202-5265, United States

University of Iowa College of Medicine, Iowa City, Iowa 52242, United States

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States

University of Massachusetts Memorial Medical Center, Worcester, Massachusetts 01655, United States

Henry Ford Hospital, Detroit, Michigan 48202, United States

University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0752, United States

University of Nebraska Medical Center, Omaha, Nebraska 68198-3330, United States

Albert Einstein Comprehensive Cancer Center, Bronx, New York 10461, United States

Cancer Center of Albany Medical Center, Albany, New York 12208, United States

Herbert Irving Comprehensive Cancer Center, New York, New York 10032, United States

Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States

Lineberger Comprehensive Cancer Center, UNC, Chapel Hill, North Carolina 27599-7295, United States

Arthur G. James Cancer Hospital - Ohio State University, Columbus, Ohio 43210, United States

Barrett Cancer Center, The University Hospital, Cincinnati, Ohio 45219, United States

Cancer Care Ontario-London Regional Cancer Centre, London, Ontario N6A 4L6, Canada

Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada

Western Pennsylvania Cancer Institute, Pittsburgh, Pennsylvania 15224, United States

Rhode Island Hospital, Providence, Rhode Island 02903, United States

Vanderbilt Cancer Center, Nashville, Tennessee 37232-6838, United States

Simmons Cancer Center - Dallas, Dallas, Texas 75235-9154, United States

University of Texas - MD Anderson Cancer Center, Houston, Texas 77030, United States

University of Washington Medical Center, Seattle, Washington 98195-6043, United States

Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States

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

Starting date: February 1998
Last updated: May 23, 2008