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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002723
• Other study ID #: NCI-2012-02788
• Secondary ID: U10CA031946CALGB
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: February 27, 2013
• Start date: January 1996
• Est. completion date: March 2008

Study information

• Verified date: February 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 390
• Est. completion date: March 2008
• Est. primary completion date: August 2002
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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.
• 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
• 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.

Locations

Country	Name	City	State
South Africa	Pretoria Academic Hospitals	Pretoria
United States	CCOP - Ann Arbor Regional	Ann Arbor	Michigan
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Albert Einstein Comprehensive Cancer Center	Bronx	New York
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois
United States	Ireland Cancer Center	Cleveland	Ohio
United States	CCOP - Geisinger Clinic and Medical Center	Danville	Pennsylvania
United States	CCOP - Duluth	Duluth	Minnesota
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Veterans Affairs Medical Center - Madison	Madison	Wisconsin
United States	CCOP - Marshfield Medical Research and Education Foundation	Marshfield	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus	Nashville	Tennessee
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Toledo Community Hospital Oncology Program	Toledo	Ohio
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Eastern Cooperative Oncology Group, Southwest Oncology Group

Countries where clinical trial is conducted

United States,  South Africa, 

References & Publications (15)

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 metas — View Citation

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 C

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 c — View Citation

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.

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 — View Citation

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 Can — View Citation

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.

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,

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. Erratum in: J Clin Oncol. 2004 Aug 15;22(16):3434. — View Citation

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. — View Citation

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

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 prosta — View Citation

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.

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 Grou — View Citation

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:

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response	PSA levels	Week 12 and then monthly	No
Primary	Response	Radiographic evaluation	Week 12 and every 12 weeks thereafter	No
Secondary	Toxicity		pre-study, day 1, then every 2 weeks during treatment and every 8 weeks during follow up	Yes
Secondary	Survival		post treatment until patient expires	No
Secondary	Quality of Life		pre-study, 2 weeks post treatment, and every 12 weeks in follow up	No