A Phase II Study of Sorafenib (Nexavar®) Prior to Radical Prostatectomy in Patients With High-Risk Localized Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed adenocarcinoma of the prostate
- •Radical prostatectomy and lymph node dissection planned as primary therapy in a patient with acceptable surgical risk (e.g., cardiovascular, pulmonary, and functional status)
- •10 year or longer life expectancy
- •Any of the following high-risk features: Clinical stage T2b (palpable bilateral involvement) OR surgically resectable T3 OR PSA >= 20 ng/ml OR overall Gleason grade >= 8
- •No evidence of bone metastases on bone scan
- •No evidence of lymph nodes >= 2 cm in diameter on pelvic CT scan
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Hemoglobin >= 9.0 g/dl
- •Absolute neutrophil count (ANC) >= 1,500/mm^3
- •Platelet count >= 100,000/mm^3
- •Total bilirubin =< 1.5 x ULN
- •ALT =< 2.5 x the ULN
- •AST =< 2.5 x the ULN
- •INR =< 1.5 and aPTT within normal limits
- •Creatinine =< 1.5 x ULN or creatinine clearance > 60mL/min/1.73 m^2
- •Men must agree to use adequate contraception (abstinence, hormonal in female partner, or barrier method of birth control) prior to study entry, for the duration of study participation, and for at least two weeks after stopping treatment
- •Signed informed patient consent
排除标准
- •Prior therapy for prostate cancer including conventional androgen deprivation therapy, radiotherapy (external beam or brachytherapy), cryotherapy, and/or cytotoxic chemotherapy
- •Any known metastasis; patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis
- •Significant active medical illness which in the opinion of the investigator would preclude protocol treatment
- •Another malignancy, other than non-melanoma skin cancer, during the past 5 years
- •History of bleeding diathesis or unexpected surgical bleeding
- •Patients with active coagulopathy
- •Cardiac disease: Congestive heart failure > class II NYHA; patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
- •Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- •Uncontrolled hypertension, as defined by systolic blood pressure consistently in excess of 150 mmHg, or diastolic pressure consistently in excess of 90 mmHg
- •Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
- •Pulmonary hemorrhage/bleeding event >= CTCAE Grade 2 within 4 weeks of first dose of study drug
- •Any other hemorrhage/bleeding event >= CTCAE Grade 3 within 4 weeks of first dose of study drug
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
- •Patients may not be concurrently receiving any chemotherapy, immunotherapy, hormonal therapy, or molecular targeted agents to treat their prostate cancer
- •Patients may not be receiving any other investigational agents
- •Therapeutic anticoagulation with heparin, low-molecular weight heparin, or warfarin within the last 4 weeks
- •Patients may not be using rifampin, digoxin, quinidine, ketoconazole, itraconazole, cyclosporine, carbamazepine, phenytoin, phenobarbital, St. John's Wart, or products containing grapefruit juice
- •Patients may not be using bevacizumab or any other drugs that target VEGF or VEGF receptors
- •Active clinically significant infections (>= grade 2 NCI-CTCAE version 3.0); patients may enroll after infection resolves
- •HIV-positive patients receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with Sorafenib
- •Any condition that impairs patient's ability to swallow whole pills
- •Any malabsorption problem
研究组 & 干预措施
Treatment (enzyme inhibitor) 48hr stop
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.
干预措施: microarray analysis (Genetic)
Treatment (enzyme inhibitor) 48hr stop
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.
干预措施: sorafenib tosylate (Drug)
Treatment (enzyme inhibitor) 48hr stop
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.
干预措施: immunohistochemistry staining method (Other)
Treatment (enzyme inhibitor) 48hr stop
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.
干预措施: gene expression analysis (Genetic)
Treatment (enzyme inhibitor) 48hr stop
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.
干预措施: needle biopsy (Procedure)
Treatment (enzyme inhibitor) 48hr stop
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.
干预措施: therapeutic conventional surgery (Procedure)
Treatment (enzyme inhibitor) 48hr stop
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.
干预措施: laboratory biomarker analysis (Other)
Treatment (enzyme inhibitor) 48hr stop
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.
干预措施: western blotting (Genetic)
Treatment (enzyme inhibitor) 48hr stop
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.
干预措施: RNA analysis (Genetic)
Treatment (enzyme inhibitor) 24hr stop
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.
干预措施: sorafenib tosylate (Drug)
Treatment (enzyme inhibitor) 24hr stop
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.
干预措施: microarray analysis (Genetic)
Treatment (enzyme inhibitor) 24hr stop
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.
干预措施: immunohistochemistry staining method (Other)
Treatment (enzyme inhibitor) 24hr stop
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.
干预措施: gene expression analysis (Genetic)
Treatment (enzyme inhibitor) 24hr stop
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.
干预措施: needle biopsy (Procedure)
Treatment (enzyme inhibitor) 24hr stop
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.
干预措施: therapeutic conventional surgery (Procedure)
Treatment (enzyme inhibitor) 24hr stop
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.
干预措施: laboratory biomarker analysis (Other)
Treatment (enzyme inhibitor) 24hr stop
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.
干预措施: western blotting (Genetic)
Treatment (enzyme inhibitor) 24hr stop
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.
干预措施: RNA analysis (Genetic)
结局指标
主要结局
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.
时间窗: Pre- versus post-treatment
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.
次要结局
- Number of Participants With Complete Pathologic Response(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(Day 1 of cycles 2 and 3 and on the day of radical prostatectomy. Each cycle is 2 weeks.)
研究者
Evan Y. Yu, MD
Principal Investigator
University of Washington