Apalutamide With Radiotherapy and Androgen Deprivation Therapy in Prostate Cancer

• Status: Withdrawn
• Trial end date: 2026-06-15
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Treatments: Androgen Antagonists; Androgens; Hormones; Nonsteroidal Anti-Androgens

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