APALUTAMIDE for Prostate adenocarcinoma | Biochemically relapsed prostate cancer

Inclusion criteria

• {"criterion_text":"-Patients must have signed a written informed consent form prior to any trial specific procedures"}
• {"criterion_text":"-Adequate renal function: serum creatinine < 1.5 x upper limit of normal (ULN) or a calculated corrected creatinine clearance ≥ 60 mL/min according to the Cockcroft-Gault formula, creatinemia < 2 ULN"}
• {"criterion_text":"-Adequate hepatic function: total bilirubin ≤ 1.5 x ULN (unless documented Gilbert’s syndrome), AST and ALT ≤ 2.5 x ULN"}
• {"criterion_text":"-Patients with QTc prolongation < 500 ms*, inclusion should considered after close benefit/risk assessment and cardiologist advice *In patients with a history or risk factors for QT prolongation, and in patients receiving concomitant medicines that may prolong the QT interval, a cardiologist should assess the benefit / risk balance taking into account the potential risk of torsade de pointes before initiating treatment with apalutamide"}
• {"criterion_text":"-Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations"}
• {"criterion_text":"-Patients must be affiliated to the Social Security System"}
• {"criterion_text":"-Age ≥ 18 years old and ≤ 80 years old"}
• {"criterion_text":"-Histologically confirmed diagnosis of prostate adenocarcinoma treated primarily with radical prostatectomy"}
• {"criterion_text":"-Tumor stage pT2, pT3 or pT4* (*only in case of bladder neck involvement)"}
• {"criterion_text":"-Patients should have no clinical and radiological signs (18FCH-PET CT-scan or 68Ga-PSMA-PET CT-scan) of metastatic disease. Patients with a local relapse or pelvic nodal relapse (N1) detected on PET CT-scan can be randomized"}
• {"criterion_text":"-ECOG performance status ≤ 1"}
• {"criterion_text":"-PSA ≥ 0.2 ng/mL at the time of randomization with an elevation of PSA over three consecutive PSA increases over a 1-month interval minimum"}
• {"criterion_text":"-At least 3 months between radical prostatectomy and randomization"}
• {"criterion_text":"-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 or pelvic lymph node relapse (N1, ≤ 5 lymph nodes)"}

Exclusion criteria

• {"criterion_text":"-Previous treatment with hormone therapy for prostate cancer"}
• {"criterion_text":"-More than 5 (>5) pelvic lymph node relapses"}
• {"criterion_text":"-Paraaortic, thoracic or supaclavicular nodal relapse (M1a)"}
• {"criterion_text":"-History of Inflammatory bowel disease or any malabsorption syndrome or conditions that would interfere with enteral absorption"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Certain risk factors for abnormal heart rhythmas/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 > 500 ms at baseline"}
• {"criterion_text":"-Medications known to prolong QTc"}
• {"criterion_text":"-Known hypersensitivity to apalutamide or to any of its components"}
• {"criterion_text":"-Galactosemia, Glucose-galactose malabsorption or lactase deficiency"}
• {"criterion_text":"-Inability or willingness to swallow oral medication"}
• {"criterion_text":"-Individual deprived of liberty or placed under the authority of a tutor"}
• {"criterion_text":"-Uncontrolled hypertension (defined as systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 100 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment"}
• {"criterion_text":"-Patients already included in another therapeutic trial with an experimental drug or having been given an experimental drug within the 30 days before inclusion"}
• {"criterion_text":"-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)"}
• {"criterion_text":"-Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry"}
• {"criterion_text":"-Clinically significant history of liver disease consistent with Child-Pugh class B or C"}
• {"criterion_text":"-Histology other than adenocarcinoma"}
• {"criterion_text":"-Surgical or chemical castration"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Previous pelvic radiotherapy"}

Primary endpoints

• {"endpoint_text":"-The primary endpoint is the 5-year-progression free survival (PFS) accordingly to PERCIST 1.0 and RECIST 1.1 criteria. PFS idefined as time from date of randomization to date of first evidence of loco-regional recurrences, or distant metastases, or death from any cause whichever occurs first, or date of last known follow-up alive without any such events. Evidence of loco-regional recurrences is evaluated on PET CT; Evidence of distant metastases is evaluated on PET CT","definition_or_measurement_approach":"Evaluated according to PERCIST 1.0 and RECIST 1.1 criteria. PFS defined as time from randomization to first evidence of loco-regional recurrence (evaluated on PET CT), distant metastases (evaluated on PET CT), or death from any cause; or date of last known follow-up alive without events."}

Secondary endpoints

• {"endpoint_text":"-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.","definition_or_measurement_approach":"Time from randomization to death related to prostate cancer or last known follow-up alive."}
• {"endpoint_text":"-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.","definition_or_measurement_approach":"Time from randomization to death from any cause or last known follow-up; assessed at 10 years."}
• {"endpoint_text":"-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.","definition_or_measurement_approach":"Interval between randomization and first PSA elevation after 6-month treatment (PSA ≥ 0.5 ng/mL confirmed by two consecutive increases over 2 months). Monitoring schedule: every 6 months for 5 years, then annually if no biochemical relapse."}
• {"endpoint_text":"-Time to castration resistance is defined as the time from date of randomization to 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 <50 ng/dl or 1.7 nmol/l plus one of the following types of progression: - Biochemical progression - Radiologic progression:","definition_or_measurement_approach":"Time from randomization to castration resistance per EAU guidelines (Cornford Eur Urol 2017): castrate testosterone <50 ng/dl (1.7 nmol/l) plus biochemical or radiologic progression."}
• {"endpoint_text":"-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 tolerance will be evaluated up until 10 years.","definition_or_measurement_approach":"Adverse events assessed by NCI CTCAE v5.0. Acute RT toxicity = during RT up to 3 months post-RT; late RT toxicity = after 3 months. Safety/tolerance evaluated up to 10 years."}
• {"endpoint_text":"-Patient-reported outcomes: Quality of life will be assessed at baseline, at end of SRT, at end of treatment visit and at every follow up visit until disease progression by using:  EORTC QLQ-C30 questionnaire  EORTC QLQ-PR25 questionnaire  IIEF-5 questionnaire  IADL scale for patients ≥ 75 years old","definition_or_measurement_approach":"Quality of life assessed using EORTC QLQ-C30, EORTC QLQ-PR25, IIEF-5 and IADL (for ≥75 years) at specified visits (baseline, end of SRT, end of treatment, and each follow-up until progression)."}

France

Earliest CTIS Part Ii Submission Date

06-06-2024

Latest Decision Or Authorization Date

19-12-2025

Processing Time Days

561

Number Of Sites

28

Number Of Participants

429

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Janssen pharmaceutica","duties_or_roles":"Source of monetary support","organisation_type":""}