Sorafenib in Treating Patients With Metastatic or Recurrent Prostate Cancer

A Phase II Study Of BAY 43-9006 (NSC 724772; CTEP IND# 69,896) In Patients With Hormone Refractory Prostate Cancer

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase II trial is studying the effectiveness of sorafenib in treating patients who have metastatic or recurrent prostate cancer that has not responded to previous hormone therapy.

OBJECTIVES:

• Determine the efficacy of sorafenib, as measured by prostate-specific antigen response, in patients with metastatic or recurrent hormone-refractory adenocarcinoma of the prostate.

Secondary

• Determine the objective response rate and duration of response in patients treated with this drug.
• Determine the tolerability and toxicity of this drug in these patients.
• Determine time to treatment failure and overall survival in patients treated with this drug.
• Explore the relationship between measures of ras/raf pathway activation (pERK) and response to treatment in these patients.

OUTLINE: This is a non-randomized, multicenter study.

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at 4 weeks after going off study treatment and then periodically for survival. Patients with stable or responding disease, when they go off study treatment, are followed every 3 months until relapse or progression.

PROJECTED ACCRUAL: Approximately 15-25 patients will be accrued for this study within 12-18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

  • Metastatic or recurrent disease

• No curative standard therapy exists

• Hormone-refractory disease

  • Evidence of prostate-specific antigen (PSA) progression during androgen ablation therapy, including medical or surgical castration

    • Documented PSA progression after completion of prior peripheral anti-androgens

      • At least a 25% increase (≥ 5 ng/mL) over a reference value PSA with 2 consecutive rising PSAs taken ≥ 1 week apart

    • Castrate level of testosterone ≤ 1.7 nmol/L for patients on medical androgen ablation

      • Patients receiving luteinizing hormone-releasing hormone agonist therapy must continue this treatment during study participation

• PSA ≥ 10 ng/mL at the time of study entry

• Primary tumor tissue (paraffin embedded) must be available for immunohistochemistry

• Minimal symptomatic disease

  • No requirement for morphine or equivalent dose > 30 mg/day to control pain

• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No evidence of bleeding diathesis

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal

Renal

• Serum creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No myocardial infarction within the past 6 months
• No congestive heart failure
• No unstable angina
• No active cardiomyopathy
• No unstable ventricular arrhythmia
• No uncontrolled hypertension

Other

• No serious infection
• No active peptic ulcer disease
• No upper gastrointestinal or other condition that would preclude study compliance with oral medication
• No uncontrolled psychotic disorder
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to sorafenib or other study agents
• No other serious illness or medical condition that would preclude study participation
• No other malignancy within the past 5 years except adequately treated non-melanoma skin cancer or other curatively treated solid tumor

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Concurrent prophylactic filgrastim (G-CSF), sargramostim (GM-CSF), or other growth factors allowed for the management of adverse events only

Chemotherapy

• No prior chemotherapy
• No other prior cytotoxic chemotherapy

Endocrine therapy

• See Disease Characteristics
• Concurrent steroids allowed provided there has been no increase in steroid requirements within the past 4 weeks AND no increase in dose is planned

Radiotherapy

• At least 4 weeks since prior external-beam radiotherapy except low-dose non-myelosuppressive radiotherapy
• Concurrent low-dose non-myelosuppressive palliative radiotherapy allowed

Surgery

• Not specified

Other

• No prior investigational anticancer agents

• No concurrent therapeutic anticoagulation

  • Concurrent prophylactic low-dose warfarin for venous or arterial access devices allowed

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent anticancer therapy

• No other concurrent investigational therapy

• No concurrent grapefruit juice

• Concurrent bisphosphonates allowed