Apalutamide with or without Abiraterone Acetate, Gonadotropin-Releasing Hormone Analog, and Prednisone in Treating Patients with High-Risk Prostate Cancer Undergoing Surgery
This randomized phase II trial studies how well apalutamide 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 apalutamide, 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 apalutamide with or without abiraterone acetate, GnRH agonist and prednisone may work better in treating patients with prostate cancer.
- 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 computed tomography (CT)/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
- 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 1 year 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)
- Patients on warfarin
Locations & Contacts
Trial Objectives and Outline
I. To evaluate the effect of neoadjuvant 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 apalutamide orally (PO) daily for 3 months. Patients then undergo radical prostatectomy.
ARM II: Patients receive a GnRH agonist (leuprolide acetate intramuscularly [IM] or goserelin acetate subcutaneously [SC]) on day 1, apalutamide 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.
Trial Phase & Type
Rutgers Cancer Institute of New Jersey
Isaac Yi Kim
Secondary IDs NCI-2016-01496, Pro20160000563
Clinicaltrials.gov ID NCT02949284