Low, Intermediate, or High Dose Suramin in Treating Patients With Hormone-Refractory Prostate Cancer
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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. 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Prostate Cancer |
Drug: suramin Drug: Suramin |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A PHASE III STUDY OF THREE DIFFERENT DOSES OF SURAMIN (NSC #34936) ADMINISTERED WITH A FIXED DOSING SCHEDULE IN PATIENTS WITH ADVANCED PROSTATE CANCER |
- Response [ Time Frame: Week 12 and then monthly ] [ Designated as safety issue: No ]PSA levels
- Response [ Time Frame: Week 12 and every 12 weeks thereafter ] [ Designated as safety issue: No ]Radiographic evaluation
- Toxicity [ Time Frame: pre-study, day 1, then every 2 weeks during treatment and every 8 weeks during follow up ] [ Designated as safety issue: Yes ]
- Survival [ Time Frame: post treatment until patient expires ] [ Designated as safety issue: No ]
- Quality of Life [ Time Frame: pre-study, 2 weeks post treatment, and every 12 weeks in follow up ] [ Designated as safety issue: No ]
| Enrollment: | 390 |
| Study Start Date: | January 1996 |
| Study Completion Date: | March 2008 |
| Primary Completion Date: | August 2002 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Low dose suramin
Low dose suramin
|
Drug: suramin
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.
Other Name: NSC #34936
|
|
Experimental: Intermediate dose suramin
Intermediate dose suramin
|
Drug: suramin
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
Other Name: NSC #34936
|
|
Experimental: High dose suramin
High dose suramin
|
Drug: Suramin
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.
Other Name: NSC #34936
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Show 27 Study Locations| Study Chair: | Eric J. Small, MD | University of California, San Francisco |
| Study Chair: | Daniel P. Petrylak, MD | Herbert Irving Comprehensive Cancer Center |
| Study Chair: | George Wilding, MD | University of Wisconsin, Madison |
More Information
Additional Information:
Publications:
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00002723 History of Changes |
| Other Study ID Numbers: | NCI-2012-02788, U10CA031946, CALGB-9480, E-C9480, SWOG-9452, INT-0159, CDR0000064583 |
| Study First Received: | November 1, 1999 |
| Last Updated: | February 27, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Cancer Institute (NCI):
|
adenocarcinoma of the prostate stage III prostate cancer stage IV prostate cancer recurrent prostate cancer |
Additional relevant MeSH terms:
|
Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases, Male Prostatic Diseases Suramin Antinematodal Agents |
Anthelmintics Antiparasitic Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Antineoplastic Agents Trypanocidal Agents Antiprotozoal Agents |
ClinicalTrials.gov processed this record on May 22, 2013