This phase II trial is studying sorafenib tosylate and gene expression in patients undergoing surgery for high-risk localized prostate cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Studying samples of blood and tumor tissues in the laboratory from patients with prostate cancer may help doctors learn more about changes that occur in DNA after treatment with sorafenib tosylate
PRIMARY OBJECTIVES: I. To compare the gene expression changes (transcript profiles) between pre- and post-treatment tumor specimens in order to determine the molecular impact of multi-kinase inhibition on prostate cancer. While this analysis will initially be targeted to tumor cells, gene expression changes in the surrounding stromal tissue may also be analyzed. SECONDARY OBJECTIVES: I. To determine if specific downstream protein effectors (i.e. ERK, AKT, and S6- kinase) of Sorafenib kinase targets are affected by changes in protein phosphorylation by immunohistochemistry. II. To provide evidence that Sorafenib has significant anti-tumor effect by comparison of pre- and post-treatment immunohistochemical markers of apoptosis (caspase-3), cell proliferation (Ki-67), and angiogenesis (microvessel density). III. To determine the pathologic complete response rate, defined as absence of cancer in the prostatectomy specimen. IV. To determine rates of positive surgical margins, extracapsular extension, seminal vesicle and lymph node involvement with tumor in comparison with Memorial Sloan Kettering pre-operative nomogram predictions. V. To determine the percentage of patients with a \>= 25% and \>= 50% decline in PSA while receiving Sorafenib. VI. To determine tissue Sorafenib levels in prostate tumors after treatment and correlate with molecular, clinical, and/or pathologic outcomes. VII. To describe changes in overall histology after treatment with Sorafenib and correlate with molecular and clinical outcomes. VIII. To determine if patients with baseline alterations in phospho-ERK, phospho-AKT, and phospho-S6-kinase expression correlate with treatment related molecular, clinical, and/or pathologic outcomes. IX. To collect tissue samples for future analysis of correlative biomarkers of prognosis or treatment response. X. To collect frozen plasma for future analysis of correlative biomarkers of treatment response (no genetic analysis will be performed on these specimens). OUTLINE: Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 or 2 days after completion of sorafenib tosylate, patients undergo radical prostatectomy on approximately day 43. After completion of study treatment, patients are followed up for 6-10 weeks.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Given PO
Correlative studies
Correlative studies
Correlative studies
Correlative studies
Undergo prostatectomy
Correlative studies
Correlative studies
Correlative studies
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Efficacy as Assessed by Number of Patients With Changes Across Transcript Profiles by Microarray Analysis in Prostate Cancer Specimens, Specifically Those With Complete Pathologic Response.
Determined by changes across transcript profiles, by microarray analysis, in pre- versus post-treatment prostate cancer specimens (minimum 50 day time frame between these). Proportion of patients with complete pathologic response.
Time frame: Pre- versus post-treatment
Number of Participants With Complete Pathologic Response
Proportion of Patients with at least 50% decline in PSA on Day 1 of Cycle 2, Day 1 of Cycle 3, and on day of radical prostatectomy.
Time frame: Day 1 of cycles 2 and 3, and day of radical prostatectomy. Each cycle is 2 weeks.
Number of Participants With at Least 25% Reduction in PSA
Proportion of Patients with at least 25% decline in PSA on Day 1 of Cycle 2, Day 1 of Cycle 3, and on day of radical prostatectomy.
Time frame: Day 1 of cycles 2 and 3 and on the day of radical prostatectomy. Each cycle is 2 weeks.
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