PARALLEL PHASE III RANDOMIZED TRIALS FOR HIGH-RISK PROSTATE CANCER EVALUATING DE-INTENSIFICATION FOR LOWER GENOMIC RISK AND INTENSIFICATION OF CONCURRENT THERAPY FOR HIGHER GENOMIC RISK WITH RADIATION (PREDICT-RT*)
Objective
This phase III trial compares less intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in treating patients with high-risk prostate cancer and low gene risk score. This trial also compares more intense hormone therapy and radiation therapy to usual hormone therapy and radiation therapy in patients with high risk prostate cancer and high gene risk score. Abiraterone acetate may help fight prostate cancer by lowering the amount of testosterone made by the body.
Study Arms
- Active Comparator: RT + ADT for 24 months (De-Intensification)
- Experimental: RT + ADT for 12 months (De-Intensification)
- Active Comparator: RT + ADT for 24 months (Intensification)
- Experimental: RT + ADT, Apalutamide, Abiraterone w/Pred. (Intensification)
Eligibility
PRIOR TO STEP 1 REGISTRATION
- Pathologically proven diagnosis of adenocarcinoma of prostate cancer within 180 days prior to registration
- High-risk disease defined as having at least one or more of the following:
- PSA > 20 ng/mL prior to starting ADT
- cT3a-T4 by digital exam or imaging (American Joint Committee on Cancer [AJCC] 8th edition [Ed.])
- Gleason score of 8-10
- Node positive by conventional imaging with a short axis of at least 1.0 cm
- Appropriate stage for study entry based on the following diagnostic workup:
- History/physical examination within 120 days prior to registration;
- Bone imaging within 120 days prior to registration;
- Note: To be eligible, patient must have no definitive evidence of bone metastases (M0) on bone scan or sodium fluoride (NaF) PET within 120 days prior to registration (negative Na F PET/CT or negative axumin or choline PET or negative fluciclovine, choline or prostate-specific membrane antigen (PSMA) PET within 120 days prior to registration is an acceptable substitute if they have been performed). Patients who have bone metastases established only fluciclovine, choline, or PSMA PET but not definitive on bone scan or Na F PET will still be eligible
- CT or MRI of the pelvis within 120 days prior to registration (negative fluciclovine, choline, or PSMA PET within 120 days prior to registration is an acceptable substitute). As with bone staging, nodal staging for trial purposes will be based off of conventional imaging findings only
- Patients with confirmed N1 metastases on conventional imaging (CT/MRI) as defined by > 10 mm on short axis are eligible but will be automatically assigned to the intensification study. Patients who are positive by fluciclovine, choline, or PSMA PET (i.e. N1), but whose nodes do not meet traditional size criteria for positivity (i.e. they measure =< 10 mm on either the CT or MRI portion of the PET or on a dedicated CT or MRI) will not be considered N1 for the trial and will not automatically be assigned to the intensification study
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days prior to registration
- Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors (within 120 days prior to registration)
- Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factors (within 120 days prior to registration)
- Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault equation (within 120 days prior to registration)
- For Black patients whose renal function is not considered adequate by Cockcroft-Gault formula, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) may be used for calculating creatinine clearance for trial eligibility
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) within 120 days prior to registration
- 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
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (within 120 days prior to registration)
- Serum albumin >= 3.0 g/dL (within 120 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 60 days prior to registration. Note: HIV testing is not required for eligibility for this protocol. Of note, for patients with HIV in the intensification trial randomized to abiraterone acetate and apalutamide, highly active antiretroviral therapy (HAART) may need to be adjusted to medications that do not interact with abiraterone acetate and apalutamide
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable after or on suppressive therapy within 60 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
- 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 or low-grade non-muscle invasive bladder cancer) who has been disease-free for less than 3 years must contact the principal investigator
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
PRIOR TO STEP 2 RANDOMIZATION
- Confirmation of Decipher score
- 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 60 days prior. Note: Apalutamide may interfere with HCV drugs. Patients on HCV medications should alert their infectious diseases physician if they get randomized to apalutamide due to the possibility that apalutamide can affect the bioavailability of some HCV medications. HCV viral testing is not required for eligibility for this protocol
- For patients entering the Intensification Cohort ONLY: Patients must discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to Step 2 randomization
- For patients entering the Intensification Cohort ONLY: Serum potassium >= 3.5 mmol/L prior to Step 2 randomization
