Prostate Cancer
Conditions
Keywords
Apalutamide Prostate Cancer Radiotherapy
Brief 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.
Interventions
OTHERRadiation Therapy
Dose escalated Intensity-Modulated Radiation therapy (IMRT) with conventional fractionation, hypofractionation and prostate brachytherapy are allowed.
DRUGApalutamide
240 mg PO daily, started the same day as the first LHRHa injection, for 6 months
DRUGLuteinising Hormone Releasing Hormone analog agonist (LHRHa)
2 injections of a three-monthly LHRH agonist depot
DRUGNon-steroidal anti-androgen
Non-steroidal anti-androgen (e. g. flutamide, bicalutamide) PO daily for 4 weeks, started 2 weeks before the first LHRH agonist injection
Sponsors
European Organisation for Research and Treatment of Cancer - EORTC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free survival | 7.8 years from First Patient In (FPI) | Events for this endpoint include loco-regional recurrence, distant metastases (radiologically or pathologically confirmed), death from any cause, whichever occurs first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distant Metastasis-free survival | 7.8 years from First Patient In (FPI) | — |
| Overall survival | 7.8 years from First Patient In (FPI) | — |
| Prostate cancer specific survival | 7.8 years from First Patient In (FPI) | — |
| Progression-free survival | 7.8 years from First Patient In (FPI) | includes first events of biochemical failure by Phoenix criteria in addition to the events listed in the primary endpoint DFS |
| Adverse events graded according to the National Cancer Institute Common Occurrence of Adverse Events | 7.8 years from First Patient In (FPI) | Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 4.0 |
| Health-related quality of life | 7.8 years from First Patient In (FPI) | Health-related quality of life will be evaluated using self-administered EORTC QLQ-C30 questionnaire |
| Prostate-Specific Antigen (PSA) nadir | 5.5 years from First Patient In (FPI) | Prostate-Specific Antigen (PSA) nadir will be assessed as the lowest value achievement on treatment |
| Prostate-Specific Antigen (PSA) value | 5.5 years from First Patient In (FPI) | Prostate-Specific Antigen (PSA) value will be assessed at the end of the treatment of each patient |
Outcome results
None listed