Hormone Therapy (Apalutamide) and Image-guided Stereotactic Body Radiation Therapy for the Treatment of Patients with Prostate Cancer, HEATWAVE Trial

Open to males ages 18 years and up

• Confirmed diagnosis of prostate adenocarcinoma
• Age ≥ 18
• Classified as having National Comprehensive Cancer Network unfavorable intermediate risk prostate cancer (i.e., [a] 2 of the following: PSA 10-20 ng/mL, clinical T category 2b-2c, or International Society of Urological Pathology [ISUP] grade group 2; [b] OR any 1 of [a] with ISUP grade group 3 disease; OR [c] any 1 of [a] with 50% or more cores on systematic biopsy showing prostate cancer)
• Have a Decipher genomic classifier score
• Have at least one dominant intraprostatic lesion visible on multiparametric MRI (Prostate Imaging-Reporting and Data System [PI-RADS] version 2.1 score 4 or 5)
• Have underwent a prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)
• Have total testosterone >= 150 ng/dL
• Adequate performance status (Eastern Cooperative Oncology Group [ECOG] 0-1)
• Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization (at screening)
• Platelet count ≥ 100,000 x 10⁹/uL independent of transfusion and/or growth factors within 3 months prior to randomization (at screening)
• Serum albumin ≥ 3.0 g/dL (at screening)
• Glomerular filtration rate (GFR) ≥ 45 mL/min (at screening)
• Serum potassium ≥ 3.5 mmol/L (at screening)
• Serum total bilirubin ≤ 1.5 x 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 may be eligible) (at screening)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x ULN (at screening)
• Medications known to lower the seizure threshold (see list under prohibited medications) must be discontinued or substituted at least 4 weeks prior to study entry

• Any evidence of spinal cord compression (radiological or clinical)
• Prior pelvic malignancy
• Prior pelvic radiation
• Concurrent malignancy other than adequately treated basal cell or squamous cell skin cancer, non-muscle invasive bladder cancer (NMIBC), or any other cancer in situ currently without evidence of recurrence or progression
• Inability to undergo radiotherapy, or hormonal therapy
• Primary small cell carcinoma of the prostate (prostate adenocarcinoma with neuroendocrine differentiation is allowed)
• Inflammatory bowel disease or active collagen vascular disease
• History of any of the following:
  • Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to 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 (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
• Current evidence of any of the following:
  • Uncontrolled hypertension
  • Gastrointestinal disorder affecting absorption
  • Known active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)
  • Any condition that in the opinion of the investigator would preclude participation in this study
  • Treatment with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, a dose reduction of the CYP2D6 substrate may be considered
  • Baseline moderate and severe hepatic impairment (Child Pugh class B & C)