Apalutamide With Radiotherapy and Androgen Deprivation Therapy in Prostate Cancer (ARN-509)
Prostate Cancer
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Apalutamide Prostate Cancer Radiotherapy
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed diagnosis of prostate adenocarcinoma diagnosed by ultrasound guided biopsy of the prostate containing 10-12 cores showing no neuroendocrine component
- Either of: Favorable intermediate risk (according to EAU risk groups): PSA 10-20 ng/mL, -or Gleason score 7 (3 +4) (ISUP Grade 2), or cT2b. Infavorable intermediate risk (according to EAU risk groups): PSA 10-20 ng/mL, -or Gleason score 7 (4+3) (ISUP Grade 3), or cT2b. Limited high risk : PSA > 20 ng/mL or Gleason score >7 (ISUP Grade 4/5)
- M0 by standard imaging work-up
- Scheduled to be treated with primary prostate RT
- WHO Performance Status ≤ 2
- No risk of urinary retention based on the International Prostate Symptom Score (IPSS) : IPSS < 20
- Adequate liver function determined by the following: aspartate aminotransferase (AST), alanine aminotransferase (ALT), < 2.5 x upper limit of normal (ULN). Total bilirubin <1.5 x upper limit of normal (ULN)
- Adequate renal function: creatinine level < 2 x ULN
- Serum albumin ≥ 3.0 g/dL
- Serum potassium ≥ 3.5 mmol/L
- Hemoglobin ≥ 10.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
- Platelet count ≥ 100,000 x 109/L independent of transfusion and/or growth factors within 3 months prior to randomization
- Be able to swallow whole study drug tablets
Exclusion Criteria:
- cT2c, T3, T4 or pelvic lymph nodes involvement, as assessed by CT scan or MRI (cN1) or pelvic lymph node dissection (pN1)
- Previous pelvic irradiation or radical prostatectomy.
- Bilateral orchiectomy
- Prior systemic (e.g., chemotherapy) or procedural (e.g., prostatectomy, cryotherapy) treatment for prostate cancer
- Prior treatment with 5-alpha reductase inhibitors for benign prostatic hypertrophy not discontinued 4 weeks prior to randomization
- Prior treatment with any LHRH agonist or antagonist, bicalutamide, flutamide or nilutamide, enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents for prostate cancer
- Prior treatment with radiopharmaceutical agents (e.g., strontium-89) or immunotherapy for prostate cancer
- Other malignancy except adequately treated basal cell carcinoma of the skin or other malignancy from which the patient has been cured for at least 5 years.
- History of Ulcerative Colitis, Crohn's Disease, Ataxia Telangiectasia, systemic lupus erythematosus or Fanconi anemia
- History of seizure or condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤ 1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect).
- Medications known to lower the seizure thresholdmust be discontinued or substituted at least 4 weeks prior to study entry
- Certain risk factors for abnormal heart rhythms/QT prolongation: torsade de pointes ventricular arrhythmias (e.g., heart failure, hypokalemia, or a family history of a long QT syndrome), a QT or corrected QT (QTc) interval > 450 ms at baseline
- Uncontrolled hypertension (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg); patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
- Bilateral hip prostheses
- Prior treatment with systemic glucocorticoids ≤ 4 weeks prior to randomization or is expected to require long-term use of corticosteroids during the study
- Use of any investigational agent ≤ 4 weeks prior to randomization
- Current chronic use of opioid analgesics for ≥3 weeks for oral or ≥ 7 days for non-oral formulations
- Major surgery ≤ 4 weeks prior to randomization
- Known or suspected contraindications or hypersensitivity to apalutamide, bicalutamide or LHRHa agonists or any of the components of the formulations
- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm A: ADT + radiation therapy
Arm B: ADT + radiation therapy + Apalutamide
Patient will receive 2 injections of a three-monthly LHRH agonist depot plus non-steroidal anti-androgen (rescue treatment) (e. g. flutamide, bicalutamide) PO daily for 4 weeks, started 2 weeks before the first LHRH agonist injection. All patients will receive standard fractionation radiation therapy (RT) between 0 and 12 weeks after first injection of LHRH agonist.
Patients will receive 2 injections of a three-monthly LHRH agonist depot. Apalutamide treatment: 240 mg PO daily, started the same day as the first LHRHa injection, for 6 months. All patients will receive standard fractionation radiation therapy (RT) between 0 and 12 weeks after first injection of LHRH agonist.