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
Overview
- Phase
- Phase 3
- Intervention
- Salvage radiotherapy (SRT)
- Conditions
- Prostate Cancer
- Sponsor
- UNICANCER
- Enrollment
- 490
- Locations
- 14
- Primary Endpoint
- Progression-free survival (PFS)
- Status
- Active, not recruiting
- Last Updated
- 9 months ago
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
SRT + 6 months of LHRHa
* 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)
SRT + 6 months of LHRHa
* 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)
SRT + 6 months of LHRHa + 6 months of Apalutamide
* 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
SRT + 6 months of LHRHa + 6 months of Apalutamide
* 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)
SRT + 6 months of LHRHa + 6 months of Apalutamide
* 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)
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)