A Phase II Study of Sorafenib (Nexavar®) Prior to Radical Prostatectomy in Patients With High-Risk Localized Prostate Cancer
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.
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
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
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
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
IX. To collect tissue samples for future analysis of correlative biomarkers of prognosis or
X. To collect frozen plasma for future analysis of correlative biomarkers of treatment
response (no genetic analysis will be performed on these specimens).
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Efficacy as assessed by changes across transcript profiles by microarray analysis in prostate cancer specimens
Determined by changes across transcript profiles, by microarray analysis, in pre- versus post-treatment prostate cancer specimens.
Pre- versus post-treatment
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Institutional Review Board
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|