Randomized Three-Arm Trial to Evaluate the Effect of Neoadjuvant Apalutamide Alone or in Combination With Abiraterone Acetate and GnRH Agonist on Enhancing Surgical Outcome of Nerve-Sparing Radical Prostatectomy in Men With High-Risk Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- Post-surgical potency rate defined as successful intercourse in half the attempts
研究概览
简要总结
This randomized phase II trial studies how well androgen receptor antagonist ARN-509 works with or without abiraterone acetate, gonadotropin-releasing hormone agonist, and prednisone in treating patients with high-risk prostate cancer undergoing surgery. Androgen can cause the growth of prostate cancer cells. Hormone therapy using androgen receptor antagonist ARN-509, abiraterone acetate, and gonadotropin-releasing hormone analog (GnRH agonist) may fight prostate cancer by lowering the levels of androgen the body makes. Prednisone may either kill the tumor cells or stop them from dividing. Giving androgen receptor agonist ARN-509 with or without abiraterone acetate, GnRH agonist and prednisone may work better in treating patients with prostate cancer.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the effect of neoadjuvant androgen receptor antagonist ARN-509 (apalutamide) with or without abiraterone acetate, GnRH agonist, and prednisone on the feasibility of performing nerve-sparing radical prostatectomy (RP) in men with high-risk prostate cancer (PCa).
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive androgen receptor antagonist ARN-509 orally (PO) daily for 3 months. Patients then undergo radical prostatectomy.
ARM II: Patients receive GnRH agonist subcutaneously (SC) on day 1, androgen receptor antagonist ARN-509 PO daily PO for 4 times, abiraterone acetate PO daily for 4 times, and prednisone PO daily for 3 months. Patients then undergo radical prostatectomy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically proven adenocarcinoma of the prostate and: Gleason > 8 OR prostatic specific antigen (PSA) > 20 and more than 1 positive core
- •Patients with Eastern Cooperative Oncology Group performance scale (ECOG PS) 0 or 1
- •Clinical stage T3 or less as demonstrated by abdominal/pelvic computed tomography (CT) or magnetic resonance imaging (MRI) will be selected as the prostate is resectable
- •Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
- •Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factors within 3 months prior to randomization
- •Serum albumin >= 3.0 g/dL
- •Glomerular filtration rate (GFR) >= 45 mL/min
- •Serum potassium >= 3.5 mmol/L
- •Serum total bilirubin =< 1.5 × upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 × ULN, subject may be eligible)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 × ULN
- •Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry
- •Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug; must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug
排除标准
- •Clinical stage T4 (invasion into rectum or ureters) significantly increases the morbidity of the surgery
- •Patients with rectal or ureteral invasion will be considered to have unresectable disease
- •History of any of the following:
- •Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)
- •Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial within 6 months prior to randomization
- •Venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks) within 6 months prior to randomization
- •Clinically significant ventricular arrhythmias within 6 months prior to randomization
- •Metastatic prostate cancer
- •Baseline moderate or severe hepatic impairment (Child-Pugh class B or C)
研究组 & 干预措施
Arm I (androgen receptor ARN-509, radical prostatectomy)
Patients receive androgen receptor antagonist ARN-509 PO daily for 3 months. Patients then undergo radical prostatectomy.
干预措施: Androgen Receptor Antagonist ARN-509 (Drug)
Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)
Patients receive GnRH agonist SC on day 1, androgen receptor antagonist ARN-509 PO daily PO for 4 times, abiraterone acetate PO daily for 4 times, and prednisone PO daily for 3 months. Patients then undergo radical prostatectomy.
干预措施: Gonadotropin-releasing Hormone Analog (Biological)
Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)
Patients receive GnRH agonist SC on day 1, androgen receptor antagonist ARN-509 PO daily PO for 4 times, abiraterone acetate PO daily for 4 times, and prednisone PO daily for 3 months. Patients then undergo radical prostatectomy.
干预措施: Quality-of-Life Assessment (Other)
Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)
Patients receive GnRH agonist SC on day 1, androgen receptor antagonist ARN-509 PO daily PO for 4 times, abiraterone acetate PO daily for 4 times, and prednisone PO daily for 3 months. Patients then undergo radical prostatectomy.
干预措施: Radical Prostatectomy (Procedure)
Arm I (androgen receptor ARN-509, radical prostatectomy)
Patients receive androgen receptor antagonist ARN-509 PO daily for 3 months. Patients then undergo radical prostatectomy.
干预措施: Quality-of-Life Assessment (Other)
Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)
Patients receive GnRH agonist SC on day 1, androgen receptor antagonist ARN-509 PO daily PO for 4 times, abiraterone acetate PO daily for 4 times, and prednisone PO daily for 3 months. Patients then undergo radical prostatectomy.
干预措施: Androgen Receptor Antagonist ARN-509 (Drug)
Arm I (androgen receptor ARN-509, radical prostatectomy)
Patients receive androgen receptor antagonist ARN-509 PO daily for 3 months. Patients then undergo radical prostatectomy.
干预措施: Questionnaire Administration (Other)
Arm I (androgen receptor ARN-509, radical prostatectomy)
Patients receive androgen receptor antagonist ARN-509 PO daily for 3 months. Patients then undergo radical prostatectomy.
干预措施: Radical Prostatectomy (Procedure)
Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)
Patients receive GnRH agonist SC on day 1, androgen receptor antagonist ARN-509 PO daily PO for 4 times, abiraterone acetate PO daily for 4 times, and prednisone PO daily for 3 months. Patients then undergo radical prostatectomy.
干预措施: Questionnaire Administration (Other)
Arm III (radical prostatectomy)
Patients undergo radical prostatectomy.
干预措施: Quality-of-Life Assessment (Other)
Arm III (radical prostatectomy)
Patients undergo radical prostatectomy.
干预措施: Questionnaire Administration (Other)
Arm III (radical prostatectomy)
Patients undergo radical prostatectomy.
干预措施: Radical Prostatectomy (Procedure)
Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)
Patients receive GnRH agonist SC on day 1, androgen receptor antagonist ARN-509 PO daily PO for 4 times, abiraterone acetate PO daily for 4 times, and prednisone PO daily for 3 months. Patients then undergo radical prostatectomy.
干预措施: Prednisone (Drug)
Arm II (ARN-509, abiraterone acetate, GnRH, prednisone, RP)
Patients receive GnRH agonist SC on day 1, androgen receptor antagonist ARN-509 PO daily PO for 4 times, abiraterone acetate PO daily for 4 times, and prednisone PO daily for 3 months. Patients then undergo radical prostatectomy.
干预措施: Abiraterone Acetate (Drug)
结局指标
主要结局
Post-surgical potency rate defined as successful intercourse in half the attempts
时间窗: At 12 months
Each of the experimental arms will be compared to the surgery-only arm, so each test will be a 2.5% level one-sided test to control for the fact that there are two comparisons.
次要结局
- Postoperative potency rate as determined by the Sexual Health Inventory for Men and EPIC questionnaire(Up to 24 months after surgery)
- Change in tumor volume on pelvic MRI after neoadjuvant therapy(Baseline to week 13)
- Number of patients with positive surgical margins(Up to 5 years)
- Quality of life as assessed by the EPIC questionnaires(Up to 24 months after surgery)
- Quality of life as assessed by the AUAss questionnaires(Up to 24 months after surgery)
- Number of patients with biochemical recurrence defined using the Prostate Cancer Clinical Trials Working Group 2 definition(Up to 5 years)
- Number of patients with pathological T0(Up to 5 years)
- Postoperative continence rate as determined by the American Urological Association Symptom Score (AUAss)(Up to 24 months after surgery)
- Postoperative continence rate as determined by the Expanded Prostate Cancer Index Composite (EPIC)(Up to 24 months after surgery)
研究者
Saum Ghodoussipour
Associate Professor of Surgery, RWJMS
Rutgers, The State University of New Jersey