NCT04181203Active, not recruitingPhase 3
An Open Label, Randomized, Phase III Study, Evaluating the Efficacy of a Combination of Apalutamide With Radiotherapy and LHRH Agonist in High-risk Postprostatectomy Biochemically Relapsed Prostate Cancer Patients
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- UNICANCER
- Enrollment
- 490
- Locations
- 14
- Primary Endpoint
- Progression-free survival (PFS)
Study Overview
Brief Summary
This is a multicenter, randomized, open label, phase III study comparing the efficacy and safety of apatulamide combined with concomitant prostate-bed salvage radiotherapy (SRT) and androgen deprivation therapy (ADT) versus concomitant prostate-bed SRT and ADT in high-risk postprostatectomy biochemically relapsed prostate cancer patients.
Detailed Description
The purpose of the CARLHA-2 study is to determine if the combination of apalutamide with 6 months of LHRH agonists and radiotherapy results in an improvement of progression-free survival (PFS) in comparison to the combination of 6 months of LHRH agonists with radiotherapy in high-risk postprostatectomy biochemically relapsed prostate cancer patients.
Radical prostatectomy must have been done at least 6 months before inclusion and is not part of this study.
Patients after radical prostatectomy and biochemical relapse will be randomized in a 1:1 ratio to receive either 6 months of LHRH agonists + SRT or 6 months of LHRH agonists + SRT + 6 months of apalutamide.
The stratification variables include Gleason score, prostate-specific antigen (PSA), negative resection margins, extension to seminal vesicle(s), and PSA doubling time.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients must have signed a written informed consent form prior to any trial specific procedures
- •Age ≥18 years old and ≤80 years old
- •Histologically confirmed diagnosis of prostate adenocarcinoma treated primarily with radical prostatectomy
- •Tumor stage pT2, pT3 or pT4* (*only in case of bladder neck involvement)
- •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
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •PSA ≥0.2 ng/mL at the time of randomization with an elevation of PSA over three consecutive assays. PSA increases over a 1-month interval minimum
- •At least 3 months between radical prostatectomy and randomization.
- •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)
- •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
- •Adequate hepatic function: total bilirubin ≤1.5 x ULN (unless documented Gilbert's syndrome), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN
- •Patients with QTc prolongation <500 ms, inclusion should considered after close benefit/risk assessment and cardiologist advice
- •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
- •Patients must be affiliated to the Social Security System
Exclusion Criteria
- •Previous treatment with hormone therapy for prostate cancer
- •Histology other than adenocarcinoma
- •Surgical or chemical castration
- •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
- •Previous pelvic radiotherapy
- •More than 5 (>5) pelvic lymph node relapses
- •Paraaortic, thoracic or supaclavicular nodal relapse (M1a)
- •History of Inflammatory bowel disease or any malabsorption syndrome or conditions that would interfere with enteral absorption
- •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
- •Clinically significant history of liver disease consistent with Child-Pugh class B or C
- •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)
- •Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry
- •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
- •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 >500 ms at baseline
- •Medications known to prolong QTc
- •Known hypersensitivity to apalutamide or to any of its components
- •Galactosemia, Glucose-galactose malabsorption or lactase deficiency
- •Inability or willingness to swallow oral medication
- •Individual deprived of liberty or placed under the authority of a tutor
- •Patients already included in another therapeutic trial with an experimental drug or having been given an experimental drug within the 30 days before inclusion
Arms & Interventions
SRT + 6 months of LHRHa
Active Comparator
- Treatment with LHRHa will start 4 weeks before the first RT fraction (i.e Day 1 of Week 1 of treatment period.) The total duration of the LHRHa treatment is 6 months.
- SRT will start 4 weeks after the first administration of LHRHa (i.e Day 1 of Week 5 of treatment period.). The total duration of SRT is 6.5 weeks.
Intervention: Salvage radiotherapy (SRT) (Radiation)
SRT + 6 months of LHRHa
Active Comparator
- Treatment with LHRHa will start 4 weeks before the first RT fraction (i.e Day 1 of Week 1 of treatment period.) The total duration of the LHRHa treatment is 6 months.
- SRT will start 4 weeks after the first administration of LHRHa (i.e Day 1 of Week 5 of treatment period.). The total duration of SRT is 6.5 weeks.
Intervention: Luteinising Hormone Releasing Hormone agonist (LHRHa) (Drug)
SRT + 6 months of LHRHa + 6 months of Apalutamide
Experimental
- Treatment with LHRHa will start 4 weeks before the first RT fraction (i.e Day 1 of Week 1 of treatment period.) The total duration of the LHRHa treatment is 6 months.
- Treatment with apalutamide (240 mg PO daily) should start the same day as the first LHRHa administration, for 6 months.
- SRT will start 4 weeks after the first administration of LHRHa (i.e Day 1 of Week 5 of treatment period.). The total duration of SRT is 6.5 weeks.
Intervention: Apalutamide (Drug)
SRT + 6 months of LHRHa + 6 months of Apalutamide
Experimental
- Treatment with LHRHa will start 4 weeks before the first RT fraction (i.e Day 1 of Week 1 of treatment period.) The total duration of the LHRHa treatment is 6 months.
- Treatment with apalutamide (240 mg PO daily) should start the same day as the first LHRHa administration, for 6 months.
- SRT will start 4 weeks after the first administration of LHRHa (i.e Day 1 of Week 5 of treatment period.). The total duration of SRT is 6.5 weeks.
Intervention: Salvage radiotherapy (SRT) (Radiation)
SRT + 6 months of LHRHa + 6 months of Apalutamide
Experimental
- Treatment with LHRHa will start 4 weeks before the first RT fraction (i.e Day 1 of Week 1 of treatment period.) The total duration of the LHRHa treatment is 6 months.
- Treatment with apalutamide (240 mg PO daily) should start the same day as the first LHRHa administration, for 6 months.
- SRT will start 4 weeks after the first administration of LHRHa (i.e Day 1 of Week 5 of treatment period.). The total duration of SRT is 6.5 weeks.
Intervention: Luteinising Hormone Releasing Hormone agonist (LHRHa) (Drug)
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: 5 years
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.
Secondary Outcomes
- Biochemical relapse-free survival(10 years)
- Cancer-specific overall survival(10 years)
- Overall survival (OS)(10 years)
- Time to castration resistance(10 years)
- Adverse events graded according to the NCI Common Terminology Criteria for Adverse Events version 5.0(Throughout study completion, up to 10 years)
- Quality of life questionnaire - Core 30 (QLQ-C30)(At baseline, 3 months, 6 months, every 6 months up to 5 years then every 12 months up to 10 years)
- Quality of Life Questionnaire - Prostate Cancer Module (QLQ-PR25)(At baseline, 3 months, 6 months, every 6 months up to 5 years then every 12 months up to 10 years)
- International Index of Erectile Function (IIEF-5)(At baseline, 3 months, 6 months, every 6 months up to 5 years then every 12 months up to 10 years)
- Lawton Instrumental Activities of Daily Living (IADL) Scale(At baseline, 3 months, 6 months, every 6 months up to 5 years then every 12 months up to 10 years)
Investigators
Study Sites (14)
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