Sorafenib Tosylate and Gene Expression Analysis in Patients Undergoing Surgery For High-Risk Localized Prostate Cancer
Adenocarcinoma of the Prostate
Stage II Prostate Cancer
Stage III Prostate Cancer
Drug: sorafenib tosylate
Genetic: microarray analysis
Other: immunohistochemistry staining method
Genetic: gene expression analysis
Procedure: needle biopsy
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Genetic: western blotting
Genetic: RNA analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Sorafenib (Nexavar®) Prior to Radical Prostatectomy in Patients With High-Risk Localized Prostate Cancer|
- Efficacy as assessed by changes across transcript profiles by microarray analysis in prostate cancer specimens [ Time Frame: Pre- versus post-treatment ] [ Designated as safety issue: No ]Determined by changes across transcript profiles, by microarray analysis, in pre- versus post-treatment prostate cancer specimens.
- PSA decline of greater than or equal to 25% and 50% [ Time Frame: Day 1 of cycles 2 and 3 and on the day of radical prostatectomy ] [ Designated as safety issue: No ]
- Complete pathologic response [ Time Frame: Day 1 of cycles 1 and 3, and day 43 ] [ Designated as safety issue: No ]
|Study Start Date:||December 2006|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor)
Patients receive sorafenib tosylate PO 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.
Drug: sorafenib tosylate
Other Names:Genetic: microarray analysis
Other Name: gene expression profilingOther: immunohistochemistry staining method
Other Name: immunohistochemistryGenetic: gene expression analysis
Correlative studiesProcedure: needle biopsy
Other Names:Procedure: therapeutic conventional surgery
Undergo prostatectomyOther: laboratory biomarker analysis
Correlative studiesGenetic: western blotting
Other Names:Genetic: RNA analysis
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 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).
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00466752
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Evan Yu||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|