Clinical trial NCT00003293: SU-101 Compared With Procarbazine in Treating Patients With Glioblastoma Multiforme
Official title: A Phase III Randomized Study of SU101 Versus Procarbazine for Patients With Glioblastoma Multiforme in First Relapse
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain and Central Nervous System Tumors
Keywords: recurrent adult brain tumor
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2004-06-03
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

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