A Phase II Randomized Study of Enzalutamide+Leuprolide Versus Enzalutamide+Leuprolide+Abiraterone Acetate+Prednisone as Neoadjuvant Therapy for HIgh-Risk Prostate Cancer Undergoing Prostatectomy

Dana-Farber Cancer Institute4 个研究点分布在 1 个国家目标入组 75 人开始时间: 2014年10月最近更新: 2022年4月19日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: Dana-Farber Cancer Institute
入组人数: 75
试验地点: 4
主要终点: Percentage of Participants With Pathologic Complete Response (pCR) or Minimal Residual Disease (MRD)

研究概览研究设计入排标准研究组 & 干预措施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 is comparing the effectiveness of enzalutamide with or without abiraterone acetate for men with high-risk, localized prostate cancer.

详细描述

In this research study, the investigators are comparing the effectiveness of enzalutamide with or without abiraterone acetate for men with high-risk, localized prostate cancer.

Abiraterone acetate with prednisone and enzalutamide are currently FDA-approved for use in the treatment of patients with metastatic castration-resistant prostate cancer, however they are investigational for the treatment of localized prostate cancer. Abiraterone acetate works by decreasing the production of male sex hormones, which cause prostate cancer growth. Enzalutamide works by blocking the effects of male sex hormones, which cause prostate cancer growth.

The FDA (the U.S. Food and Drug Administration) has not approved the combination of enzalutamide and abiraterone acetate as neoadjuvant therapy for high risk prostate cancer undergoing prostatectomy but each drug has been approved for the treatment of more advanced prostate cancer.

Participants will be randomized to one of two study arms. Randomization means that the participant is put into a group by chance. It is like flipping a coin. Neither participant nor the research doctor will choose what group participants are randomized to.

The names of the study medications involved in this study are:

研究设计

研究类型: Interventional
分配方式: Randomized
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

•Male greater than or equal 18 years of age.
•Histologically confirmed adenocarcinoma of the prostate without histological variants (including overt neuroendocrine differentiation, small cell neuroendocrine carcinoma features, sarcomatoid features, pure ductal adenocarcinoma, squamous or transitional cell carcinoma).
•Must have tissue available from the pre-treatment diagnostic biopsy (tissue blocks if possible; if not possible, 10 unstained slides from each positive core sample for a total of 30 slides).
•Must have three core biopsies involved with cancer (a minimum of 6 core biopsies must be obtained). Prostate biopsy must be within three months from screening.
•Participants must have the following features:
•Intermediate-risk disease defined as Gleason 4+3=7 disease OR
•High-risk disease defined as Gleason 8-10 OR PSA > 20 ng/dL OR T3 disease (by prostate MRI)
•No evidence of metastatic or nodal disease as determined by radionuclide bone scans CT/MRI.
•Participants must be candidates for RP and considered surgically resectable by urologic evaluation.
•ECOG performance status 0 to 1 (Appendix A).
•Participants must have normal organ and marrow function as defined below:
•WBC ≥ 3,000/mcL
•ANC ≥ 1,500/mcL
•Platelets ≥ 100,000/mcL
•Serum potassium ≥ 3.5 mmol/L
•AST, ALT, and total bilirubin ≤ 1.5 x Institutional ULN
•Calculated creatinine clearance ≥ 60 mL/min
•PTT ≤ 60, INR ≤ 1.5 x Institutional ULN unless on warfarin therapy (investigator would need to determine if safe for participant to stop warfarin prior to biopsy and warfarin therapy)
•Controlled blood pressure defined as a systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg on no more than three anti-hypertensive agents. Drug formulations containing two or more anti-hypertensive agents will be counted based on the number of active agents in each formulation.

排除标准

•Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens (including first-generation antiandrogens, enzalutamide, ARN-509 and others), CYP17 inhibitors (including abiraterone, TAK-700, galeterone, ketoconazole, and others), estrogens, LHRH agonist/antagonists. Prior therapy with 5α-reductace inhibitors is allowed. LHRH therapy allowed if begun within 4 weeks of day
•Prior chemotherapy, radiation therapy, or immunotherapy for prostate cancer.
•Prior systemic treatment with an azole drug within four weeks of screening visit.
•Hypogonadism or severe androgen deficiency as defined by screening serum testosterone < 200 ng/dL.
•Clinically significant cardiovascular disease including:
•Acute coronary syndrome within 6 months of screening visit;
•Hypotension defined as a systolic blood pressure < 86 mmHg;
•Bradycardia defined as a heart rate of < 50 beats per minute, unless pharmaceutically induced and thus reversible (i.e. beta blockers);
•Uncontrolled angina (requiring escalating doses of nitrates) within 3 months of screening visit;
•Congestive heart failure NYHA Class III or IV or subjects with a history of congestive heart failure NYHA Class III or IV, unless screening ECHO results in left ventricular ejection fraction that ≥ 45%;
•History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes);
•Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on screening EKG > 470 msec;
•History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
•History of seizure or any condition or concurrent medication that may predispose to seizure.
•Thromboembolism within 6 months of screening visit.
•Severe hepatic impairment (Child-Pugh Class C).
•Active or symptomatic viral hepatitis or chronic liver disease.
•History of pituitary or adrenal dysfunction.
•GI disorders which may interfere with the absorption of the study drug.
•Pre-existing condition that warrants long-term corticosteroid use.
•Concomitant use of medications that may alter pharmacokinetics of abiraterone or enzalutamide.
•Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1) individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, or 2) individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: non-muscle invasive bladder cancer, basal cell or squamous cell carcinoma of the skin.
•Major surgery or radiation therapy within 30 days of screening.