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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003293
• Other study ID #: SUGEN-SU101.015
• Secondary ID: CDR0000066226MSK
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: September 10, 2012
• Start date: February 1998
• Est. completion date: May 2001

Study information

• Verified date: September 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: May 2001
• Est. primary completion date: May 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioblastoma
• Nervous System Neoplasms

Intervention

Drug:
• leflunomide

• procarbazine hydrochloride

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	Cancer Center of Albany Medical Center	Albany	New York
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Medical College of Georgia Hospital and Clinics	Augusta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Albert Einstein Comprehensive Cancer Center	Bronx	New York
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	University of Colorado Cancer Center	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	University of Iowa College of Medicine	Iowa City	Iowa
United States	Beckman Research Institute, City of Hope	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt Cancer Center	Nashville	Tennessee
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Western Pennsylvania Cancer Institute	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	St. Francis Hospital	San Francisco	California
United States	University of Washington Medical Center	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Arizona Cancer Center	Tucson	Arizona
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada,