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

This study has been completed.
Sponsor:
Collaborators:
Southwest Oncology Group
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00002723
First received: November 1, 1999
Last updated: February 27, 2013
Last verified: February 2013
  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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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
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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002723

  Show 27 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Eastern Cooperative Oncology Group
Investigators
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:
Taplin ME, George DJ, Halabi S, et al.: Prognostic significance of plasma chromogranin A levels in hormone-refractory prostate cancer patients treated on Cancer and Leukemia Group B (CALGB) 9480. [Abstract] J Clin Oncol 22 (Suppl 14): A-4557, 396s, 2004.
Bok R, Halabi S, Shaal M, et al.: VEGF and basic FGF urine levels as predictors of response to therapy with suramin in CALGB 9480, a phase III study of hormone refractory prostate cancer (HRPC) patients. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A1367, 2000.
Halabi S, Small EJ, Ansari RH, et al.: Results of CALGB 9480, a phase III trial of 3 different doses of suramin for the treatment of horomone refractory prostate cancer (HRPC). [Abstract] Proceedings of the American Society of Clinical Oncology 19: A1291, 2000.
Kantoff P, Halabi S, Farmer D, et al.: RT-PCR for prostate specific antigen (PSA) in peripheral blood (PB) predicts survival duration in patients with hormone refractory prostate cancer (HRPC): a CALBG study. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A1323, 2000.
Vogelzang N, Small E, Halabi R, et al.: A phase III trial of 3 different doses of suramin (SUR) in metastatic hormone refractory prostate cancer (HRPC): safety profile of CALGB 9480. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A1339, 347a, 1998.
D'Amico AV, Halabi S, Vogelzang NJ, et al.: A reduction in the rate of PSA rise following chemotherapy in patients with metastatic hormone refractory prostate cancer (HRPC) predicts survival: results of a pooled analysis of CALGB HRPC trials. [Abstract] J Clin Oncol 22 (Suppl 14): A-4506, 383s, 2004.
Gilligan TD, Halabi S, Kantoff PW, et al.: African-American race is associated with longer survival in patients with metastatic hormone-refractory prostate cancer (HRCaP) in four randomized phase III Cancer and Leukemia Group B (CALGB) trials. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-725, 2002.

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 Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Suramin
Anthelmintics
Anti-Infective Agents
Antinematodal Agents
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses
Trypanocidal Agents

ClinicalTrials.gov processed this record on November 23, 2014