Low, Intermediate, or High Dose Suramin in Treating Patients With Hormone-Refractory Prostate Cancer

Study Overview
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Brief Summary
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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. 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.

Detailed Description
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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. 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.

Official Title
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A PHASE III STUDY OF THREE DIFFERENT DOSES OF SURAMIN (NSC #34936) ADMINISTERED WITH A FIXED DOSING SCHEDULE IN PATIENTS WITH ADVANCED PROSTATE CANCER

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: suramin
* Drug: suramin
* Drug: Suramin


Participation Criteria
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Eligibility Criteria
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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 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 PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy for metastatic disease Chemotherapy: No prior chemotherapy (including estramustine) for metastatic disease Endocrine therapy: 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) Other: No prior experimental therapy for metastatic disease No concurrent heparin, warfarin, or aspirin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose suramin<br>Low dose suramin | Drug: suramin<br>* 3.192g/square meter total dose given decreasing concentrations in 250 cc normal saline IV over 1 hour on days 1,2,8,9,29,30,36,37,57,58,64,and 65.<br>* Other names: NSC #34936;|
| Experimental: Intermediate dose suramin<br>Intermediate dose suramin | Drug: suramin<br>* 5.320 g/square meter total dose given in decreasing concentrations in 250 cc normal saline via IV over 1 hour on days 1,2,8,9,29,30,36,37,57,58,64,and 65<br>* Other names: NSC #34936;|
| Experimental: High dose suramin<br>High dose suramin | Drug: Suramin<br>* 7.661 g/square meter toal dose given in decreasing concentrations in 250 cc normal saline IV over 1 hour on days 1,2,8,9,29,30,36,37,5,58,64,and 65.<br>* Other names: NSC #34936;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response | PSA levels | Week 12 and then monthly | 
| Response | Radiographic evaluation | Week 12 and every 12 weeks thereafter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | pre-study, day 1, then every 2 weeks during treatment and every 8 weeks during follow up | 
| Survival |  | post treatment until patient expires | 
| Quality of Life |  | pre-study, 2 weeks post treatment, and every 12 weeks in follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage III prostate cancer, stage IV prostate cancer, recurrent prostate cancer