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 which regimen of suramin is more effective for prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of low, intermediate, and high dose suramin in treating men with stage IV prostate cancer that is refractory to hormone therapy.

Condition	Treatment or Intervention	Phase
stage III prostate cancer stage IV prostate cancer adenocarcinoma of the prostate recurrent prostate cancer	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: growth factor antagonist therapy  Procedure: anti-cytokine therapy  Drug: suramin	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the response in patients with advanced hormone-refractory adenocarcinoma of the prostate treated with low- vs intermediate- vs high-dose suramin. II. Compare the toxic effects of these regimens in these patients. III. Compare the overall and failure-free survival of patients treated with these regimens. IV. Compare the duration of complete and partial responses in patients treated with these regimens. V. Determine the population pharmacokinetics of these regimens and correlate these parameters with the toxicity of these regimens and response rate in these patients. VI. Compare the quality of life of patients treated with these regimens. VII. Determine the relationship of absolute and relative decrease in PSA and rate of PSA decrease with the likelihood and duration of response in patients treated with these regimens. VIII. Determine whether a change in fibroblast growth factor levels in patients treated with suramin can be associated with the pharmacokinetics of suramin or the likelihood of clinical response in these patients.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease site (bone only vs soft tissue), CALGB/Zubrod performance status (0 or 1 vs 2), number of prior hormonal therapies (1 or 2 vs 3), and participating center. Patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive low-dose suramin IV over 1 hour on days 1, 2, 8, 9, 29, 30, 36, 37, 57, 58, 64, and 65 in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive intermediate-dose suramin as in arm I. Arm III: Patients receive high-dose suramin as in arm I. Patients with new progression after partial or complete response may receive additional courses, at the discretion of the study chairperson, beginning at least 12 weeks after completion of the first course and continuing in the absence of disease progression or unacceptable toxicity. Quality of life is assessed. Patients are followed every 4 weeks until disease progression and then periodically for new primary cancer(s) and survival.

PROJECTED ACCRUAL: A total of 378 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven adenocarcinoma of the prostate with progressive metastatic or progressive regional nodal disease; PSA evidence of progression defined as at least 50% increase over baseline on at least 2 measurements at least 2 weeks apart
• Measurable disease preferred but not required; Bone scan abnormalities acceptable provided PSA at least 10 ng/mL; No minimum PSA value required if measurable disease present
• Progression after or during an adequate trial of hormonal therapy; No more than 3 prior hormonal interventions for progressive disease; One prior hormonal intervention is defined by any of the following: Concurrent testicular and adrenal androgen ablation (e.g., leuprolide, goserelin, orchiectomy, or diethylstilbestrol (DES) plus flutamide, bicalutamide, nilutamide, megestrol, or other antiandrogen); Initial LHRH agonist followed by orchiectomy provided no progression prior to orchiectomy; Prior intermittent androgen deprivation on protocol SWOG-9346; Corticosteroids for metastatic disease or in conjunction with aminoglutethimide or ketoconazole; Two prior hormonal interventions are defined by the following: Antiandrogen given for disease progression more than 3 months after initial hormonal therapy
• Prior neoadjuvant or adjuvant deprivation for treatment of nonmetastatic disease not considered a prior hormonal intervention
• Antiandrogen withdrawal not considered a separate hormonal intervention; At least 4 weeks since antiandrogen withdrawal or megestrol withdrawal; Failure to respond to (i.e., no decrease in PSA at 2 and 4 weeks) or progression after a transient response to antiandrogen withdrawal or megestrol withdrawal required
• Primary testicular androgen suppression (e.g., LHRH agonist or DES) continues during study
• No brain metastases or other CNS disease

--Prior/Concurrent Therapy--

• Biologic therapy: No prior immunotherapy for metastatic disease
• Chemotherapy: No prior chemotherapy (including estramustine) for metastatic disease
• Endocrine therapy: See Disease Characteristics; No concurrent megestrol or other hormonal agents; No concurrent systemic or inhaled corticosteroids (intranasal and topical steroids allowed)
• Radiotherapy: At least 4 weeks since prior radiotherapy (8 weeks for strontium therapy)
• Surgery: See Disease Characteristics
• Other: No prior experimental therapy for metastatic disease; No concurrent heparin, warfarin, or aspirin

--Patient Characteristics--

• Age: 18 and over
• Performance status: CALGB 0-2 OR Zubrod 0-2
• Life expectancy: At least 3 months
• Hematopoietic: WBC at least 3,000/mm3; Absolute neutrophil count at least 1,200/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 9 g/dL; Fibrinogen at least 200 mg/dL; No prior hemorrhagic or thrombotic disorders
• Hepatic: Bilirubin normal; AST/ALT no greater than 2.5 times normal; Prothrombin time, partial thromboplastin time, and thrombin time normal
• Renal: Creatinine clearance at least 70 mL/min
• Other: No primary muscle disease; No active, uncontrolled bacterial, viral, or fungal infection; No grade 1 or worse peripheral neuropathy ;No underlying medical condition that would preclude study; No other serious medical illness that limits survival to less than 3 months; No psychiatric condition that would preclude informed consent; No other malignancy within the past 5 years except inactive nonmelanomatous skin cancer or adequately treated stage I or II cancer in remission

Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States
      Veterans Affairs Medical Center - Lakeside Chicago, Chicago,  Illinois,  60611,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States
Michigan
      CCOP - Ann Arbor Regional, Ann Arbor,  Michigan,  48106,  United States
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States
New Jersey
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07018-1095,  United States
New York
      Albert Einstein Comprehensive Cancer Center, Bronx,  New York,  10461,  United States
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
Ohio
      CCOP - Toledo Community Hospital Oncology Program, Toledo,  Ohio,  43623-3456,  United States
      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States
Pennsylvania
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center, Nashville,  Tennessee,  37232-6838,  United States
      Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus, Nashville,  Tennessee,  37212,  United States
Wisconsin
      CCOP - Marshfield Medical Research and Education Foundation, Marshfield,  Wisconsin,  54449,  United States
      Medical College of Wisconsin, Milwaukee,  Wisconsin,  53226,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States
      Veterans Affairs Medical Center - Madison, Madison,  Wisconsin,  53705,  United States
      Veterans Affairs Medical Center - Milwaukee (Zablocki), Milwaukee,  Wisconsin,  53295,  United States
South Africa
      Pretoria Academic Hospitals, Pretoria,  0001,  South Africa

Study chairs or principal investigators

Richard L. Schilsky,  Study Chair,  Cancer and Leukemia Group B   
Charles A. Coltman, Jr.,  Study Chair
George Wilding,  Study Chair

Study ID Numbers:  CDR0000064583; CLB-9480; INT-0159
Record last reviewed:  October 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002723
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08