Clinical trial NCT02949284: Androgen Receptor Antagonist ARN-509 With or Without Abiraterone Acetate, Gonadotropin-Releasing Hormone Analog, and Prednisone in Treating Patients With High-Risk Prostate Cancer Undergoing Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Stage II Prostate Adenocarcinoma
Stage III Prostate Adenocarcinoma
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2016-10-31
Enrollment: 90
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

ARM III: Patients undergo radical prostatectomy.

After completion of study treatment, patients are followed up for 2 years.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Post-surgical potency rate defined as proportion of patients with International Index of Erectile Function score >= 17
timeFrame: At 12 months
Secondary outcomes:
measure: Change in tumor volume on pelvic MRI after neoadjuvant therapy
timeFrame: Baseline to week 13
measure: Number of patients with biochemical recurrence defined using the Prostate Cancer Clinical Trials Working Group 2 definition
timeFrame: Up to 5 years
measure: Number of patients with pathological T0
timeFrame: Up to 5 years
measure: Number of patients with positive surgical margins
timeFrame: Up to 5 years
measure: Postoperative continence rate as determined by the American Urological Association Symptom Score (AUAss)
timeFrame: Up to 24 months after surgery
measure: Postoperative continence rate as determined by the Sexual Health Inventory for Men
timeFrame: Up to 24 months after surgery
measure: Postoperative continence rate as determined by the Expanded Prostate Cancer Index Composite (EPIC)
timeFrame: Up to 24 months after surgery
measure: Quality of life as assessed by the AUAss questionnaires
timeFrame: Up to 24 months after surgery
measure: Quality of life as assessed by the EPIC questionnaires
timeFrame: Up to 24 months after surgery
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Saum Ghodoussipour, MD
role: PRINCIPAL_INVESTIGATOR
References: