High-risk biochemically-relapsed prostate adenocarcinoma following radical prostatectomy. MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Apalutamide
Product Code: JNJ-56021927
Pharmaceutical Form: Tablet
INN or Proposed INN: APALUTAMIDE
CAS Number: 204420
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
UNICANCER
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Patients must have signed a written informed consent form prior to any trial specific procedures 2. Age = 18 years old and = 80 years old 3. Histologically confirmed diagnosis of prostate adenocarcinoma treated primarily with radical prostatectomy 4. Pathologically proven to be lymph node negative by pelvic lymphadenectomy (N0) or lymph node status pathologically unknown (undissected pelvic lymph nodes [Nx]) 5. Tumor stage pT2, pT3 or pT4* (*only in case of bladder neck involvement) 6. Patients should have no clinical and radiological signs (18FCH-PET CT-scan or 68Ga-PSMA-PET) of metastatic disease. Patients with a local relapse detected on PET scan be randomized 7. ECOG performance status = 1 8. PSA = 0.1 ng/mL after radical prostatectomy (dosage performed within 3 months after surgery) 9. PSA = 0.2 ng/mL and = 2 ng/mL at the time of randomization with an elevation of PSA over three consecutive assays 10. At least 6 months between radical prostatectomy and biochemical relapse 11. High-risk features as defined by at least one of these characteristics: PSA at relapse > 0.5 ng/mL or Gleason score > 7 or tumor stage pT3b or resection margins R0 or PSA doubling time = 6 months 12. Adequate renal function: serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 290
Exclusion criteria
Exclusion criteria: 1. Histologically proven lymph nodes involvement at initial lymphadenectomy: pN1,pN2, pN3 2. Previous treatment with hormone therapy for prostate cancer 3. Histology other than adenocarcinoma 4. Surgical or chemical castration 5. 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 6. Previous pelvic radiotherapy 7. History of Inflammatory bowel disease or any malabsorption syndrome or conditions that would interfere with enteral absorption 8. Uncontrolled hypertension (defined as systolic blood pressure (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 9. Clinically significant history of liver disease consistent with Child-Pugh class B or C 10. History of seizure or condition that may pre-dispose 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) 11. Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry 12. Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g pulmonary embolism, cerebrovascular accident including transient ischemic attacks) or clinically significant ventricular arrhythmias within 6 months prior to randomization 13. Known hypersensitivity to apalutamide or to any of its components 14. Galactosemia, Glucose-galactose malabsorption or lactase deficiency 15. Inability or willingness to swallow oral medication 16. Individual deprived of liberty or placed under the authority of a tutor 17. Patients already included in another therapeutic trial with an experimental drug or having been given an experimental drug within the 30 days before inclusion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the clinical benefit of adding the androgen receptor competitive inhibitor apalutamide in combination with a Luteinizing Hormone Releasing Hormone (LHRH) agonist concomitantly to salvage radiotherapy (SRT) after biochemical progression following radical prostatectomy in patients with high-risk prostate adenocarcinoma. The clinical benefit will be evaluated using the progression-free survival (PFS) rate at 5 years.;Secondary Objective: 1. To evaluate the prostate-cancer specific survival rate 2. To evaluate the overall survival rate at 10 years 3. To evaluate the biochemical relapse rate 4. To evaluate the time to castration resistant prostate cancer 5. To evaluate safety 6. To assess patients’ quality of life;Primary end point(s): The primary endpoint is the 5-year-progression free survival (PFS). PFS is defined as the time from the date of randomization to the date of first evidence of loco-regional recurrences, or distant metastases, or death from any cause whichever occurs first, or the date of last known follow-up alive without any such events. Evidence of loco-regional recurrences is evaluated on PET CT (18FCH-PET CT-scan or 68Ga-PSMA PET) Evidence of distant metastases is evaluated on PET CT (18FCH-PET CT-scan or 68Ga- PSMA PET) Relapse at a distant metastatic site is defined as the occurrence of PET CT defined bone or soft tissue distant metastasis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: 1. Cancer-specific overall survival is defined as the time from the date of randomization to the date of death related to prostate cancer or the date of last known follow-up alive. 2. Overall survival (OS) will be assessed at 10 years. OS is defined as the time from the date of randomization to the date of death from any cause or the date of last known follow-up alive. 3. Biochemical relapse-free survival will be retrospectively defined by the interval between the date of randomization and the date of the first PSA elevation following the 6-months treatment in both arms (PSA = 0.5 ng/mL confirmed by two consecutive PSA increases over a 2-months interval). If no biochemical relapse is observed, the PSA concentration will be measured every 6 months for 5 years and every year thereafter. In order to compare PSA values, PSA assays must always be performed for each patient in the same laboratory. Following biochemical relapse, clinical staging (18FCH-PET CT-scan or 68Ga-PSMA PET) will be repeated every 6 months until local or metastatic progression is detected. 4. The time to castration resistance is defined as the time from the date of randomization to the date of appearance of castration resistance defined in the EAU guidelines (Cornford Eur Urol 2017). Castration-resistant prostate cancer (CRPC) is defined as castrate serum testosterone 2 ng/ml - Radiologic progression: The appearance of new lesions: either two or more new bone lesions on bone scan or a soft tissue lesion using the Response Evaluation Criteria in Solid Tumours Safety: Frequency, nature and severity of adverses events will be assessed according to the NCI CTCAE version 5.0 (see Appendix 4) Acute toxicity related to radiotherapy is defined as occurring during radiotherapy and up to 3 months after completion of radiotherapy. Late toxicity related to radiotherapy is defined as occurring later than 3 months after end of radiotherapy. The toler | — |
Countries
France
Contacts
Public ContactProject Manager
UNICANCER
Outcome results
None listed