临床试验/NCT02159690

NCT02159690撤回2 期

A Phase II Neoadjuvant Study of Enzalutamide, Abiraterone Acetate, Dutasteride and Degarelix in Men With Localized Prostate Cancer Pre-prostatectomy

Kenneth Pienta, MD2 个研究点分布在 1 个国家开始时间: 2014年9月1日最近更新: 2015年1月26日

适应症

试验速览

阶段: 2 期
状态: 撤回
发起方
试验地点: 2
主要终点: Proportion of prostatectomy specimens with a complete response rate

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This study investigates the pathologic effects of the combination of enzalutamide, abiraterone acetate, dutasteride, and degarelix when given for 12 weeks prior to prostatectomy in men with localized prostate cancer.

Enzalutamide, an androgen receptor (AR) antagonist, blocks binding of testosterone to the AR as well as preventing nuclear translocation of the AR and DNA binding. Abiraterone acetate inhibits the CYP17 pathway, which is involved in the formation of androgens. Dutasteride is a 5-alpha-reductase inhibitor which blocks conversion of testosterone to dihydrotestosterone. Degarelix, a gonadotropin-releasing hormone (GnRH) antagonist, binds to GnRH receptors on the pituitary gland thus suppressing testosterone release from the testes.

Therefore it is hypothesized that the combination of enzalutamide, abiraterone acetate, dutasteride, and degarelix will result in near-complete AR inhibition and produce favorable pathologic changes after 12 weeks of therapy.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
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

•Willing and able to provide written informed consent.
•Age ≥ 18 years
•Eastern cooperative group (ECOG) performance status ≤2
•Documented histologically confirmed adenocarcinoma of the prostate
•Willing to undergo prostatectomy as primary treatment for localized prostate cancer
•High risk prostate cancer (per NCCN criteria): Gleason score 8-10 or T3a or PSA > 20 ng/mL -Or- Very-high risk prostate cancer (per NCCN criteria): T3b -T4
•Serum testosterone ≥150 ng/dL
•Able to swallow the study drugs whole as tablets
•Willing to take abiraterone acetate on an empty stomach (no food should be consumed at least two hours before and for one hour after dosing).
•Willing to use a condom if having sex with a pregnant woman, or use a condom and another effective method of birth control if having sex with a woman of child-bearing potential. These measures are required during and for one week after treatment with abiraterone.

排除标准

•Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)
•Prior use of enzalutamide or abiraterone acetate
•Prior or ongoing systemic therapy for prostate cancer including, but not limited to:
•Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)
•CYP-17 inhibitors (e.g. ketoconazole)
•Antiandrogens (e.g. bicalutamide, nilutamide)
•Second generation antiandrogens (e.g. enzalutamide, ARN-509)
•Immunotherapy (e.g. sipuleucel-T, ipilimumab)
•Chemotherapy (e.g. docetaxel, cabazitaxel)
•Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study.
•Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
•Abnormal bone marrow function [absolute neutrophil count (ANC)<1500/mm3, platelet count <100,000/mm3, hemoglobin <9 g/dL]
•Abnormal liver function (bilirubin, AST, ALT ≥ 3 x upper limit of normal)
•Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal)
•Abnormal cardiac function as manifested by NYHA (New York Heart Association) class III or IV heart failure or history of a prior myocardial infarction (MI) within the last five years prior to enrollment in the study.
•History of prior cardiac arrhythmia.

结局指标

主要结局

Proportion of prostatectomy specimens with a complete response rate

时间窗: 12 weeks

Proportion of prostatectomy specimens with complete response rate after 12 weeks of therapy

次要结局

Proportion of radiographic disappearance of MRI detectable significant prostate nodules(12 weeks)
PSA progression free survival(2 years after last accrual)
Proportion of prostatectomy specimens with a negative surgical margin rate(12 weeks)
Proportion of prostatectomy specimens with pathologic T3 disease(12 weeks)
Change in immunologic parameters (TREC levels and antibody responses)(16 weeks)
Exploratory biomarkers assessment(16 weeks)
Proportion of prostatectomy specimens with a near-pathologic complete response(12 weeks)
Incidence and severity of adverse events(16 weeks)
Proportion of men who receive adjuvant radiation therapy within 1 year of prostatectomy(64 weeks)
Overall survival(2 years after last accrual)

研究者

发起方

Kenneth Pienta, MD

申办方类型

Other

责任方

Sponsor Investigator

主要研究者

Kenneth Pienta, MD

Principal Investigator

Johns Hopkins University

研究点 (2)

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