sorafenib in treating patients with metastatic or recurrent prostate cancer

Conditions: Prostate Cancer

Summary: 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.

Eligibility criteria:
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

Keywords: recurrent prostate cancer stage iv prostate cancer adenocarcinoma of the prostate