Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Using PET/CT Imaging

Open to males ages 18 years and up

• STEP 0: REGISTRATION ELIGIBILITY CRITERIA
• Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma
• Patient must have biochemical recurrence (BCR) after RP, with rising PSA defined as follows:
  • If time to biochemical recurrence, (defined as time to first detectable PSA after RP) is < 12 months, a minimum PSA level of >= 0.2 ng/mL and a confirmatory reading of >= 0.2 ng/mL is required, per the American Urological Association (AUA) definition (this includes patients with a persistent PSA reading of at least 0.2 ng/mL)
  • If time to biochemical recurrence, (defined as time to first detectable PSA after RP) is >= 12 months, a minimum absolute PSA of 0.5 ng/mL is required
    • NOTE: Qualifying PSA values per above must be collected at least 4 weeks after RP, with confirmatory persistent or elevated PSA collected at any subsequent time point
• Patient must be negative or equivocal for extrapelvic metastatic disease by conventional imaging modalities (CIM) (i.e., bone scans, pelvic CT, or pelvic MRI), which must be done within 10-12 weeks prior to registration. Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT fields
• Baseline PET/CT scan (PET1) are eligible for this study if the SOC PET scan using 18F-fluciclovine (Axumin) is completed during step 0 registration or up to 12 weeks prior to step 0 registration. The PET/CT scanners must meet scanner qualifications and scans must have an interpretation (or confirmation of an institutional clinical read) by a nuclear medicine physician or radiologist who has undergone 18F-fluciclovine (Axumin) reader training
• Patient must be a candidate for standard-of-care (SOC) post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (adjuvant)
• Patient must have the ability to provide written informed consent
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET/CT scan and radiation treatment planning and delivery
• Patient must be at a participating institution, which has agreed to perform the imaging research studies, completed the ECOG-American College of Radiology Imaging Network (ACRIN) defined PET/CT scanner qualification procedures and received ECOG-ACRIN PET/CT scanner approval
• Leukocytes >= 3,000/mcL (obtained within 4 weeks prior to registration)
• Absolute neutrophil count >= 1,500/mcL (obtained within 4 weeks prior to registration)
• Platelets >= 100,000/mcL (obtained within 4 weeks prior to registration)
• Total bilirubin =< institutional upper limit of normal (ULN) (obtained within 4 weeks prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 4 weeks prior to registration)
• Glomerular filtration rate (GFR) > 35 mL/min estimated by Cockcroft-Gault or measured directly by 24 hour urine creatinine (obtained within 4 weeks prior to registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• 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
• 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. To be eligible for this trial, patients should be class I or II (by patient symptoms) or A or B (by objective assessment)
• STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
• Patient must have completed a baseline SOC PET scan (PET1) with results of extra-pelvic metastases involvement known (positive or negative)
• For patients with negative extra-pelvic metastases, PET-imaging status of intra-pelvic nodes must be known (positive or negative)
• For patients with positive extra-pelvic metastases (defined as any PET positive lesions outside of standard salvage RT fields [prostate bed +/- typical whole pelvis]), the number of extra-pelvic lesions must be known (=< 5 or > 5 pelvic lesions)

• Patient must not have started androgen deprivation therapy for biochemical recurrence prior to baseline study PET/CT imaging
• Patient must not be enrolled in another therapeutic clinical trial
• Patient must not have any other malignancy within the last 2 years, other than superficial bladder cancer and skin basal cell carcinoma or cutaneous superficial squamous cell carcinoma that has not metastasized
• Patient must not have history of seizures or known condition that may cause predisposal to seizures (e.g., stroke or head trauma resulting in loss of consciousness) within 1 year of registration
• Patient must not have history of inflammatory bowel disease as this would increase risk of complication from radiotherapy or any gastrointestinal disorder affecting absorption
• Patient must not have had prior radiation therapy