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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT00003293

Collaborator

(none)

Locations

38.9

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: leflunomide Drug: procarbazine hydrochloride	Phase 3

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 1998

Actual Primary Completion Date :

May 1, 2001

Actual Study Completion Date :

May 1, 2001

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85001-2071
2	Arizona Cancer Center	Tucson	Arizona	United States	85724
3	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033-0800
4	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
5	Beckman Research Institute, City of Hope	Los Angeles	California	United States	91010
6	St. Francis Hospital	San Francisco	California	United States	94109
7	University of Colorado Cancer Center	Denver	Colorado	United States	80262
8	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida	United States	33140
9	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
10	Medical College of Georgia Hospital and Clinics	Augusta	Georgia	United States	30912-3620
11	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois	United States	60611
12	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5265
13	University of Iowa College of Medicine	Iowa City	Iowa	United States	52242
14	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
15	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts	United States	01655
16	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
17	Henry Ford Hospital	Detroit	Michigan	United States	48202
18	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-3330
19	Cancer Center of Albany Medical Center	Albany	New York	United States	12208
20	Albert Einstein Comprehensive Cancer Center	Bronx	New York	United States	10461
21	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
22	Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
23	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
24	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio	United States	45219
25	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210
26	Western Pennsylvania Cancer Institute	Pittsburgh	Pennsylvania	United States	15224
27	Rhode Island Hospital	Providence	Rhode Island	United States	02903
28	Vanderbilt Cancer Center	Nashville	Tennessee	United States	37232-6838
29	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75235-9154
30	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
31	University of Washington Medical Center	Seattle	Washington	United States	98195-6043
32	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
33	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
34	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario	Canada	N6A 4L6
35	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9