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

NCT ID: NCT00002723

Last Updated: 2013-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

390 participants

Study Classification

INTERVENTIONAL

Study Start Date

1996-01-31

Study Completion Date

2008-03-31

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.

Conditions

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Prostate Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Low dose suramin

Low dose suramin

Group Type EXPERIMENTAL

suramin

Intervention Type DRUG

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.

Intermediate dose suramin

Intermediate dose suramin

Group Type EXPERIMENTAL

suramin

Intervention Type DRUG

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

High dose suramin

High dose suramin

Group Type EXPERIMENTAL

Suramin

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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NSC #34936 NSC #34936 NSC #34936

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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SWOG Cancer Research Network

NETWORK

Sponsor Role collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eric J. Small, MD

Role: STUDY_CHAIR

University of California, San Francisco

Daniel P. Petrylak, MD

Role: STUDY_CHAIR

Herbert Irving Comprehensive Cancer Center

George Wilding, MD

Role: STUDY_CHAIR

University of Wisconsin, Madison

Locations

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Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, United States

Site Status

Veterans Affairs Medical Center - Lakeside Chicago

Chicago, Illinois, United States

Site Status

CCOP - Carle Cancer Center

Urbana, Illinois, United States

Site Status

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

CCOP - Ann Arbor Regional

Ann Arbor, Michigan, United States

Site Status

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

Site Status

CCOP - Duluth

Duluth, Minnesota, United States

Site Status

Veterans Affairs Medical Center - Minneapolis

Minneapolis, Minnesota, United States

Site Status

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

Site Status

Veterans Affairs Medical Center - East Orange

East Orange, New Jersey, United States

Site Status

CCOP - Northern New Jersey

Hackensack, New Jersey, United States

Site Status

Albert Einstein Comprehensive Cancer Center

The Bronx, New York, United States

Site Status

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Site Status

Ireland Cancer Center

Cleveland, Ohio, United States

Site Status

CCOP - Toledo Community Hospital Oncology Program

Toledo, Ohio, United States

Site Status

CCOP - Geisinger Clinic and Medical Center

Danville, Pennsylvania, United States

Site Status

CCOP - MainLine Health

Wynnewood, Pennsylvania, United States

Site Status

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

Site Status

Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus

Nashville, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Veterans Affairs Medical Center - Madison

Madison, Wisconsin, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

CCOP - Marshfield Medical Research and Education Foundation

Marshfield, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Veterans Affairs Medical Center - Milwaukee (Zablocki)

Milwaukee, Wisconsin, United States

Site Status

Pretoria Academic Hospitals

Pretoria, , South Africa

Site Status

Countries

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United States South Africa

References

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Halabi S, Vogelzang NJ, Kornblith AB, Ou SS, Kantoff PW, Dawson NA, Small EJ. Pain predicts overall survival in men with metastatic castration-refractory prostate cancer. J Clin Oncol. 2008 May 20;26(15):2544-9. doi: 10.1200/JCO.2007.15.0367.

Reference Type BACKGROUND
PMID: 18487572 (View on PubMed)

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.

Reference Type BACKGROUND

Halabi S, Small EJ, Kantoff PW, Kattan MW, Kaplan EB, Dawson NA, Levine EG, Blumenstein BA, Vogelzang NJ. Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. J Clin Oncol. 2003 Apr 1;21(7):1232-7. doi: 10.1200/JCO.2003.06.100.

Reference Type BACKGROUND
PMID: 12663709 (View on PubMed)

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.

Reference Type BACKGROUND

George DJ, Halabi S, Shepard TF, Sanford B, Vogelzang NJ, Small EJ, Kantoff PW. The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: results from cancer and leukemia group B 9480. Clin Cancer Res. 2005 Mar 1;11(5):1815-20. doi: 10.1158/1078-0432.CCR-04-1560.

Reference Type RESULT
PMID: 15756004 (View on PubMed)

Taplin ME, George DJ, Halabi S, Sanford B, Febbo PG, Hennessy KT, Mihos CG, Vogelzang NJ, Small EJ, Kantoff PW. Prognostic significance of plasma chromogranin a levels in patients with hormone-refractory prostate cancer treated in Cancer and Leukemia Group B 9480 study. Urology. 2005 Aug;66(2):386-91. doi: 10.1016/j.urology.2005.03.040.

Reference Type RESULT
PMID: 16098367 (View on PubMed)

Ahles TA, Herndon JE 2nd, Small EJ, Vogelzang NJ, Kornblith AB, Ratain MJ, Stadler W, Palchak D, Marshall ME, Wilding G, Petrylak D, Holland JC; Cancer and Leukemia Group B. Quality of life impact of three different doses of suramin in patients with metastatic hormone-refractory prostate carcinoma: results of Intergroup O159/Cancer and Leukemia Group B 9480. Cancer. 2004 Nov 15;101(10):2202-8. doi: 10.1002/cncr.20655.

Reference Type RESULT
PMID: 15484217 (View on PubMed)

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.

Reference Type RESULT

Small EJ, Halabi S, Ratain MJ, Rosner G, Stadler W, Palchak D, Marshall E, Rago R, Hars V, Wilding G, Petrylak D, Vogelzang NJ. Randomized study of three different doses of suramin administered with a fixed dosing schedule in patients with advanced prostate cancer: results of intergroup 0159, cancer and leukemia group B 9480. J Clin Oncol. 2002 Aug 15;20(16):3369-75. doi: 10.1200/JCO.2002.10.022.

Reference Type RESULT
PMID: 12177096 (View on PubMed)

Bok RA, Halabi S, Fei DT, Rodriquez CR, Hayes DF, Vogelzang NJ, Kantoff P, Shuman MA, Small EJ. Vascular endothelial growth factor and basic fibroblast growth factor urine levels as predictors of outcome in hormone-refractory prostate cancer patients: a cancer and leukemia group B study. Cancer Res. 2001 Mar 15;61(6):2533-6.

Reference Type RESULT
PMID: 11289126 (View on PubMed)

George DJ, Halabi S, Shepard TF, Vogelzang NJ, Hayes DF, Small EJ, Kantoff PW; Cancer and Leukemia Group B 9480. Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on Cancer and Leukemia Group B 9480. Clin Cancer Res. 2001 Jul;7(7):1932-6.

Reference Type RESULT
PMID: 11448906 (View on PubMed)

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.

Reference Type RESULT

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.

Reference Type RESULT

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.

Reference Type RESULT

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.

Reference Type RESULT

Other Identifiers

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U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CALGB-9480

Identifier Type: -

Identifier Source: secondary_id

E-C9480

Identifier Type: -

Identifier Source: secondary_id

SWOG-9452

Identifier Type: -

Identifier Source: secondary_id

INT-0159

Identifier Type: -

Identifier Source: secondary_id

CDR0000064583

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02788

Identifier Type: -

Identifier Source: org_study_id

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