Testing the Addition of the Drugs, Apalutamide and Abiraterone with Prednisone, to the Usual Hormone Therapy and Radiation Therapy after Surgery for Prostate Cancer
- Pathologically (histologically) proven diagnosis of prostate adenocarcinoma. Any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted
- Any T-stage is eligible
- Appropriate stage for study entry based on fluciclovine F-18 positron emission tomography (PET) scan (FACBC, Axumin) within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease; (Note that though every effort should be made to obtain a fluciclovine F-18 PET [FACBC, Axumin] scan, if the patient has already had a recent gallium Ga 68-labeled PSMA-11 [Ga-68 PSMA] PET scan or C-11 or F-18 choline PET scan within 90 days prior to registration [to include scan report] then repeat molecular imaging with a fluciclovine F-18 PET [FACBC, Axumin] scan will not be required.)
- Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen (including external iliacs, internal iliacs, and/or obturator nodes)
- History/physical examination within 90 days prior to registration
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 90 days prior to registration
- Detectable PSA after radical prostatectomy. Detectable PSA is defined as serum PSA > 0 ng/mL at least 30 days after prostatectomy and within 90 days of registration and before start of GnRH agonist/antagonist
- Patients who have already started on post-prostatectomy GnRH agonist/antagonist for =< 45 days prior to registration are eligible (Note: patients who started on an oral antiandrogen are eligible if started =< 45 days and stopped prior to registration)
- Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors (within 90 days prior to registration)
- Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factors (within 90 days prior to registration)
- Serum potassium >= 3.5 mmol/L within 90 days prior to registration
- Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault (please use actual weight for calculation unless greater than 30% above ideal body weight then use the adjusted body weight) (within 90 days prior to registration)
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert’s syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject is eligible) (within 90 days prior to registration)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (within 90 days prior to registration)
- Serum albumin >= 3.0 g/dL (within 90 days prior to registration)
- Discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to registration
- The patient must agree 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 agree 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
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (didanosine [DDI] is not permitted) with undetectable viral load within 6 months are eligible for this trial and have a CD4 count >= 200 cells/microliter within 30 days prior to registration. Note: HIV testing is not required for eligibility for this protocol
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 30 days prior to registration
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ) who has no evidence of disease for < 3 years must contact the principal investigator, Ron Chen, Doctor of Medicine (MD)
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
- Definitive radiologic evidence of metastatic disease (M1a, M1b or M1c) on molecular imaging (e.g. fluciclovine F-18 PET, PSMA, F-18 choline 11)
- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration)
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
- Current use of 5-alpha reductase inhibitor. NOTE: if the alpha reductase inhibitor is stopped prior to randomization the patient is eligible
- Didanosine (DDI) antiretroviral therapy is not permitted
- History of any of the following: * Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to registration, 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, 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 registration * New York Heart Association functional classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification.) * History of any condition that in the opinion of the investigator, would preclude participation in this study
- Current evidence of any of the following: * Known gastrointestinal disorder affecting absorption of oral medications * Active uncontrolled infection * Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment * Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily * Baseline moderate and severe hepatic impairment (Child-Pugh Class B & C) * Inability to swallow oral pills * Any current condition that in the opinion of the investigator, would preclude participation in this study
- Patients must not plan to participate in any other therapeutic clinical trials while receiving treatment on this study
West Des Moines
I. Compare metastasis-free survival (MFS) of salvage radiation therapy (RT) and gonadotropin releasing hormone (GnRH) agonist/antagonist versus (vs.) RT/GnRH agonist/antagonist with abiraterone acetate with prednisone and apalutamide for patients with pathologic node-positive prostate cancer after radical prostatectomy with detectable prostate-specific antigen (PSA).
I. Compare health-related quality of life (Expanded Prostate Cancer Index Composite [EPIC]-26, EuroQol [EQ]-5 Dimension [D]-5 Level [L]), Brief Pain Inventory, Patient Reported Outcome Measurement Information System [PROMIS]-Fatigue) among the treatment arms.
II. Compare overall survival, biochemical progression-free survival, time to local-regional progression, time to castrate resistance, and cancer-specific survival among the treatment arms.
III. Compare the short-term and long-term treatment-related adverse events among the treatment arms.
I. Validate Decipher score for an exclusively node-positive population and use additional genomic information from Affymetrix Human Exon 1.0st array to develop and validate novel prognostic and predictive biomarkers.
II. Validate the PAM50-based classification of prostate cancer into luminal A, luminal B, and basal subtypes as prognostic markers and determine whether the luminal B subtype is a predictive marker for having a larger improvement in outcome from the addition of abiraterone acetate with prednisone and apalutamide.
III. To optimize quality assurance methodologies and processes for radiotherapy and imaging with machine learning strategies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive standard of care hormone therapy per physician discretion for 24 months. Patients also undergo standard of care pelvis and prostate bed radiation therapy 5 days per week over 7-8 weeks beginning within 56 days after first hormone injection if the injection is not started prior to registration or within 90 days after first hormone injection if the injection is started prior to registration in the absence of disease progression or unacceptable toxicity.
ARM II: Patients undergo standard of care hormone therapy and radiation therapy as in Arm I. Patients also receive apalutamide orally (PO) once daily (QD), abiraterone acetate PO QD, and prednisone PO QD or twice daily (BID) on days 1-90. Cycles repeat every 90 days for 8 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 3 years, then annually thereafter.
Trial Phase Phase III
Trial Type Treatment
Ronald C. Chen
- Primary ID NRG-GU008
- Secondary IDs NCI-2019-06838
- Clinicaltrials.gov ID NCT04134260