Stage II Prostate Adenocarcinoma, Stage III Prostate Adenocarcinoma
Conditions
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.
Interventions
DRUGAbiraterone Acetate
Given PO
DRUGAndrogen Receptor Antagonist ARN-509
Given PO
BIOLOGICALGonadotropin-releasing Hormone Analog
Given SC
DRUGPrednisone
Given PO
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
PROCEDURERadical Prostatectomy
Undergo radical prostatectomy
Sponsors
National Cancer Institute (NCI)
Rutgers, The State University of New Jersey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-surgical potency rate defined as proportion of patients with International Index of Erectile Function score >= 17 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Number of patients with positive surgical margins | Up to 5 years | — |
| Postoperative continence rate as determined by the American Urological Association Symptom Score (AUAss) | Up to 24 months after surgery | — |
| Change in tumor volume on pelvic MRI after neoadjuvant therapy | Baseline to week 13 | Will be correlated with clinical outcomes before and after androgen receptor antagonist ARN-509 or androgen receptor antagonist ARN-509, GnRH agonist, prednisone plus abiraterone acetate. |
| Postoperative continence rate as determined by the Expanded Prostate Cancer Index Composite (EPIC) | Up to 24 months after surgery | — |
| Quality of life as assessed by the AUAss questionnaires | Up to 24 months after surgery | — |
| Quality of life as assessed by the EPIC questionnaires | Up to 24 months after surgery | — |
| Postoperative continence rate as determined by the Sexual Health Inventory for Men | Up to 24 months after surgery | — |
Countries
United States
Outcome results
None listed