Clinical trial NCT00466752
Conditions: Adenocarcinoma of the Prostate Stage II Prostate Cancer Stage III Prostate Cancer
Sponsor: University of Washington
Start date: 2006-12-01; Completion date: 2011-07-01
Enrollment: 5 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
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

Detailed description:
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.

Arms: arm 1: 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 2 days after completion of sorafenib tosylate, patients undergo radical prostatectomy on approximately day 43. arm 2: tients 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 day after completion of sorafenib tosylate, patients undergo radical prostatectomy on approximately day 43.
Interventions: intervention 1: sorafenib tosylate intervention 2: microarray analysis intervention 3: immunohistochemistry staining method intervention 4: gene expression analysis intervention 5: needle biopsy intervention 6: therapeutic conventional surgery intervention 7: laboratory biomarker analysis intervention 8: western blotting intervention 9: RNA analysis
Intervention descriptions: intervention 1: Given PO intervention 2: Correlative studies intervention 3: Correlative studies intervention 4: Correlative studies intervention 5: Correlative studies intervention 6: Undergo prostatectomy intervention 7: Correlative studies intervention 8: Correlative studies intervention 9: Correlative studies

Protocol documents: