Treating Prostate Cancer That Has Come Back after Surgery with Apalutamide and Targeted Radiation Based on PET Imaging, INDICATE Trial

Inclusion Criteria

• STEP 0: REGISTRATION ELIGIBILITY CRITERIA
• Patient must be male and >= 18 years of age
• Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma
• Patient must have biochemical recurrence (BCR) after RP, meeting one of the criteria below: * PSA level of ≥ 0.2 ng/mL at any time after RP if patient had first detectable PSA within 12 months after RP. First detectable = first non-zero value reported, any value higher than the lower limit of normal for that assay (Note: Patients with a persistent post-RP PSA reading of > 0.2 ng/mL are automatically eligible). OR * PSA level of ≥ 0.5 ng/mL at any time after RP if patient had first detectable PSA more than 12 months after RP. First detectable = first non-zero value reported, any value higher than the lower limit of normal for that assay. OR * NO minimum PSA requirement if the patient has a detectable PSA (any value higher than the lower limit of normal for that assay) at any time after RP AND has an eligible baseline SOC PET (PET1) with at least one positive lesion in any body location
• Patients must have no definite evidence for extrapelvic metastatic disease. This may be determined by CIM (CT abdomen/pelvis or MRI abdomen/pelvis AND bone scintigraphy or equivalent) within 26 weeks prior to step 0 registration. If patient does not have prior CIM, an existing study-eligible = PET using FDA-approved radiotracer may be used to determine whether patient requires CIM. For patients who have study-eligible PET done without prior CIM: * Baseline CIM is required if the study-eligible PET is positive for extrapelvic lesions. Patient should have a baseline CT/MRI (e.g. for soft tissue lesions) and performed within 16 weeks prior to study registration./or a bone scan (e.g. for osseous lesions), for further evaluation of the PET-detected extrapelvic lesion(s). * Baseline CIM is not required if the study-eligible PET is negative for extrapelvic lesions. NOTE: Extra-pelvic metastases are defined as extrapelvic soft tissue, lymph node and organ metastases, and/or any osseous metastases; extra-pelvic is defined as superior to common iliac bifurcation, and/or outside of standard fields for prostate bed + whole pelvis nodal RT fields
• Patient must be a candidate for SOC post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (ADT)
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patient must not have started short term ADT for biochemical recurrence prior to baseline PET (PET1), but may start short term ADT after PET and up to 7 days prior to study registration. * NOTE: A short course (e.g., ~ 4 weeks) of low-dose anti-androgen (e.g. bicalutamide), started given after PET1, either before or after study registration, is also permitted as a brief temporizing measure/bridge to protocol-approved SOC short term ADT
• Patient must not be actively receiving treatment in another therapeutic clinical trial
• Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET scan and radiation treatment planning and delivery
• Patients undergoing a PET/MR must meet local institutional safety guidelines for MRI
• 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 prior to registration
• Patient must not have history of inflammatory bowel disease or gastrointestinal disorder affecting absorption that is expected to increase risk of complication from radiotherapy to an unacceptable level, per institutional standard
• Hemoglobin (Hgb) >= 9.0 g/dL (independent of transfusion and/or growth factors within 3 months prior to Step 0 registration) (obtained within 8 weeks prior to Step 0 registration)
• Leukocytes >= 3,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Absolute neutrophil count >= 1,500/mcL (obtained within 8 weeks prior to Step 0 registration)
• Platelets >= 100,000/mcL (obtained within 8 weeks prior to Step 0 registration)
• Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (patients with Gilbert’s syndrome, if total bilirubin is > 1.5 x ULN, must have a direct bilirubin of < 1.5 x ULN to be eligible) (obtained within 8 weeks prior to Step 0 registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 8 weeks prior to Step 0 registration)
• Creatinine < 1.5 x institutional ULN (or measured creatinine clearance > 30 mL/min) (obtained within 8 weeks prior to Step 0 registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• 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)
• Patient must not have completed a course of prior pelvic external beam radiation therapy that would overlap with SOC RT fields used in this protocol, such that normal tissue constraints cannot be met
• Patient must agree not to father children while on study
• Patient must be English or Spanish speaking to be eligible for the QOL component of the study * NOTE: Sites cannot translate the associated QOL forms
• STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
• Patient must have completed a baseline SOC PET/CT or PET/MR (PET1 scan) using an FDA approved radiotracer to establish presence or absence of extra-pelvic metastases on PET (positive or negative). The PET1 must have been completed after Step 0 registration and prior to Step 1 randomization OR up to 16 weeks prior to Step 0 registration
• For patients with PET scan results that are negative for extra-pelvic metastases, PET-imaging status of intra-pelvic nodes must be known (positive or negative)
• For patients with PET scan results that are positive for 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 (1 - 5 or > 5 extra-pelvic lesions)