Conventional Androgen Deprivation Therapy with or without Abiraterone, Prednisone, and Apalutamide for the Treatment of High Risk Prostate Cancer after Radiation and Male Hormone Deprivation Therapy
- Histologically confirmed prostate cancer
- PSA > undetectable (any value at or above the lower limit of detection for the assay used) after radiation and at least 6, but not more than 8 months of conventional ADT (LHRH agonist or antagonist with or without oral anti-androgens, excluding abiraterone acetate and apalutamide) in patients with non-metastatic high risk or N1 prostate cancer * High risk is defined per the National Comprehensive Cancer Network (NCCN) guidelines – clinical, radiographic, or pathological (biopsy proven) T3, Gleason 8-10, or PSA > 20 ng/mL, and can be N0 or N1 * A month is defined as 28 days
- Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Subject must have the ability to understand and willingness to sign the written informed consent document
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Platelet count (plt) >= 100,000/uL (obtained within 3 months of registration) * Independent of transfusion and/or growth factors within 3 months prior to randomization
- Hemoglobin (Hgb) >= 9 g/dL (obtained within 3 months of registration) * Independent of transfusion and/or growth factors within 3 months prior to randomization
- Absolute neutrophil count (ANC) >= 1000 cells/uL (obtained within 3 months of registration)
- Creatine clearance (CrCl) >= 45 mL/min (obtained within 3 months of registration) * Cockcroft-Gault formula will be used to calculate creatinine clearance
- Bilirubin =< 1.5 x upper limit of normal (ULN) (obtained within 3 months of registration) * In subjects with Gilbert’s syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin; if direct bilirubin is =< 1.5 x ULN, subject may be eligible
- Aspartate aminotransferase (AST) < 2.5 x ULN (obtained within 3 months of registration)
- Alanine aminotransferase (ALT) < 2.5 x ULN (obtained within 3 months of registration)
- Serum albumin > 3.0 g/dL (obtained within 3 months of registration)
- Serum potassium >= 3.5 mmol/L (obtained within 3 months of registration)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN (unless on prophylactic or therapeutic dosing with low molecular weight heparin) (obtained within 3 months of registration)
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (unless on prophylactic or therapeutic dosing with low molecular weight heparin) (obtained within 3 months of registration)
- 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
- Ability to understand and comply with study procedures for the entire length of the study as determined by the site investigator or protocol designee
- Medications known to lower the seizure threshold must be discontinued or substituted prior to cycle 1 day 1 (C1D1) of study treatment for patients on Arm 2
- Able to swallow pills
- Prior radical prostatectomy (excluding transurethral prostatic resection [TURP] and simple prostatectomy)
- History of any of the following: * Seizure or known condition that may predispose to seizure (e.g., prior stroke within 1 year of 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 or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
- Known current evidence of any of the following: * Uncontrolled hypertension. Participants with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy * Gastrointestinal disorder affecting absorption * Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome * Known active or chronic hepatitis B infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening). Subject with past or resolved hepatitis B infection (defined as having a negative HBsAg test and positive antibody to hepatitis B core antigen test) are eligible. Hepatitis B viral deoxyribonucleic acid (DNA) must be obtained in subjects with positive hepatitis B core antibody prior to first treatment start * Active hepatitis C infection. Subjects positive hepatitis C antibody test are eligible if polymerase chain reaction (PCR) is negative for hepatitis C viral DNA * Pre-existing condition that warrants long-term corticosteroid use greater than the equivalent of 10 mg prednisone daily. Physiologic replacement is permitted. Topical, intra-articular steroids or inhaled corticosteroids are permitted * Any condition that, in the opinion of the site investigator, would preclude participation in this study * Baseline moderate or severe hepatic impairment (Child Pugh class B or C)
- Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate dosing frequency
- Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, psychiatric illness or social situations that would limit compliance with study requirements
- Individuals with a history of another malignancy are not eligible if the cancer is under active treatment or the cancer can be seen on radiology scans or if they are off cancer treatment but in the opinion of their oncologist have a high risk of relapse within 5 years
I. To evaluate whether metastasis free survival is prolonged in men undergoing novel antiandrogen therapy (ADT) (gonadotrophin releasing hormone [LHRH] agonist or antagonist, apalutamide, and abiraterone acetate with prednisone) as compared to conventional ADT with a LHRH agonist or antagonist alone in men whose prostate specific antigen (PSA) remains detectable after radiation therapy and 6-8 months of ADT for high risk prostate cancer.
I. To evaluate the PSA nadir following randomization.
II. To evaluate castrate resistant PSA failure.
III. To evaluate prostate cancer-specific survival.
IV. To evaluate overall survival.
V. To evaluate disease free survival.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive LHRH agonist or antagonist (leuprolide, goserelin, triptorelin, histrelin, or degarelix) for the duration of planned ADT (12-36 months).
ARM II: Patients receive LHRH agonist or antagonist as in Arm I. Patients also receive abiraterone acetate orally (PO) daily, prednisone PO twice daily (BID), and apalutamide PO daily for the duration of planned ADT (12-36 months) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 5 years.
Trial Phase Phase III
Trial Type Treatment
Dana-Farber Harvard Cancer Center
Anthony V. D'Amico
- Primary ID 18-530
- Secondary IDs NCI-2019-07704
- Clinicaltrials.gov ID NCT03777982