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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 3

Conditions: Prostate Cancer

Treatments: Drug: Suramin; Drug: suramin

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00002723

NCI-2012-02788

CALGB-9480

INT-0159

SWOG-9452

U10CA031946 (U.S. NIH Grant/Contract)

CDR0000064583 (Registry Identifier)

E-C9480

Details and patient eligibility

About

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.

Full 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.

Enrollment: 390 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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390 participants in 3 patient groups

Low dose suramin

Experimental group

Description:

Low dose suramin

Treatment:

Drug: suramin

Drug: suramin

Intermediate dose suramin

Experimental group

Description:

Intermediate dose suramin

Treatment:

Drug: suramin

Drug: suramin

High dose suramin

Experimental group

Description:

High dose suramin

Treatment:

Drug: Suramin