apalutamide with radiotherapy and androgen deprivation therapy in prostate cancer

Conditions: Prostate Cancer

Summary: the main objective of the trial to determine if the combination of apalutamide with 6 months of androgen deprivation therapy by lhrh agonists in patients with intermediate and limited high-risk, localized prostate cancer receiving primary radiation therapy (rt) results in an improvement of disease-free survival (dfs) evaluated by the treating physician, in comparison to the combination of radiation and androgen deprivation therapy without the addition of apalutamide.


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

Keywords: apalutamide prostate cancer radiotherapy