Darolutamide for Prostate adenocarcinoma with pelvic lymph node metastases

Inclusion criteria

• {"criterion_text":"- 1. Newly diagnosed, histologically confirmed prostate adenocarcinoma\n- 10. Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) < 2.5 x upper limit of normal (ULN), total bilirubin < 1.5 x ULN (except patients with a diagnosis of Gilbert’s disease), creatinine < 2.0 x ULN.\n- 11. Sexually active patients, unless surgically sterile, must agree to use condoms as an effective barrier method during the study treatment and for 3 months after the end of the study treatment.\n- 12. Written informed consent.\n- 13. Willing and expected to comply with follow-up schedule.\n- 14. Affiliated to the social security system.\n- 15. Use of 5-α reductase inhibitors (finasteride, dutasteride) is allowed\n- 2. ≥ 18 years old.\n- 3. Initial staging with Pelvic MRI + (contrast-enhanced body CT-scan + bone scan or Choline or PSMA PET-CT)\n- 4. Any T stage\n- 5. N stage: N1 - Pelvis lymph nodes metastases (upper limit defined as the L4/L5 interspace).\n- 6. Intention to treat with long-term androgen deprivation therapy (24 months).\n- 7. Hormonal therapy with LHRH agonist or antagonist is allowed up to 3 months prior to treatment initiation\n- 8. Able to receive protocol therapy and have life expectancy of at least 36 months, ECOG Performance Status (PS) 0-2.\n- 9. Blood counts at screening: hemoglobin ≥ 9.0 g/dl, absolute neutrophil count ≥ 1500/μl (1.5x109/l), platelet count ≥ 100,000/μl (100x109/l ) (patient must not have received any growth factor or blood transfusion within 7 days of the hematology laboratory obtained at screening)."}

Exclusion criteria

• {"criterion_text":"- 1. Lymph nodes metastases outside of the pelvis\n- 10. Any of the following within 6 months before treatment initiation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV or arterial thromboembolic event.\n- 11. Uncontrolled hypertension as indicated by a resting systolic BP > 160 mmHg or diastolic BP > 100 mmHg at screening. Patients may be re-screened after adjustments of anti- hypertensive medications.\n- 12. Prior malignancy. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e. pTis, pTa, and pT1) is allowed, as well as any other cancer for which chemotherapy has been completed > 5 years ago and from which the patient has been disease-free.\n- 13. Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment.\n- 14. Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease.\n- 15. Participation in another interventional clinical trial and any concurrent treatment with any investigational drug\n- 16. Any condition that in the opinion of the investigator would impair the patients’ ability to comply with the study procedures.\n- 17. Unable to swallow study medications and comply with study requirements\n- 18. Galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption\n- 19. History of bilateral hip replacements making IMRT impossible\n- 2. Bone or visceral metastases\n- 20. Contra-indications for the administration of any of the study treatments (RT, ADT, darolutamide/placebo) or any of its ingredients.\n- 21. Patient under guardianship, administrative curatorship and not able to give informed consent\n- 3. Prior systemic therapy for locally-advanced prostate cancer except for LHRH agonist or antagonist up to 3 months before treatment initiation\n- 4. Prior treatment with: - Second generation AR inhibitors such as enzalutamide, apalutamide (ARN-509), darolutamide (ODM-201) other investigational AR inhibitors - CYP17 enzyme inhibitor such as abiraterone acetate, TAK-700 or - Oral ketoconazole - Use of estrogens, or AR inhibitors (bicalutamide = Casodex©, flutamide, nilutamide, cyproterone acetate) within 28 days before treatment initiation.\n- 5. Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days before treatment initiation\n- 6. Patients with QTor QTc interval > 450 ms on the ECG\n- 7. Initiation of treatment with bisphosphonate or denosumab within 12 weeks before treatment initiation. Patients receiving bone loss prevention treatment on a stable dose of e.g. bisphosphonate or denosumab for at least 28 days before treatment initiation can continue the treatment during the study.\n- 8. Known hypersensitivity to the study treatment (RT, ADT, darolutamide/placebo) or any of its ingredients.\n- 9. Major surgery within 28 days before treatment initiation."}

Primary endpoints

• {"endpoint_text":"- The failure-free survival is defined as the time from the date of randomization to clinical (new cancer-related symptoms), biochemical (PSA rising above nadir + 2ng/mL, phoenix criteria) or radiological (local relapse or new metastases) progression, death, end of 5-year follow-up period or lost to follow-up, whichever occurs first.","definition_or_measurement_approach":"Defined in text: time from randomization to clinical, biochemical (PSA rise above nadir +2 ng/mL, Phoenix criteria), or radiological progression, death, end of 5-year follow-up, or lost to follow-up, whichever occurs first."}

Secondary endpoints

• {"endpoint_text":"- • Failure-free survival rates at 5 years.","definition_or_measurement_approach":"Rates of failure-free survival at 5 years (proportion of patients meeting primary endpoint criteria at 5 years)."}
• {"endpoint_text":"- • Metastasis-free survival and Metastasis-free survival rates at 5 years : Metastasis-free survival is defined as the time from the date of treatment initiation to the date of increase in the number of metastatic pelvic lymph nodes, or death due to any cause, whichever is first.","definition_or_measurement_approach":"Defined as time from treatment initiation to increase in number of metastatic pelvic lymph nodes or death from any cause, whichever is first; rates at 5 years measured."}
• {"endpoint_text":"- Progression-free survival and Progression-free survival rates at 5 years : Progression free survival is defined as the time from the date of treatment initiation to disease progression or death from any whichever is first. A progression is defined by radiological progression or biological progression or a clinical progression.","definition_or_measurement_approach":"Defined as time from treatment initiation to disease progression (radiological, biological, or clinical) or death from any cause; rates at 5 years measured."}
• {"endpoint_text":"- 4.\tTime to PSA response, Time to PSA progression and PSA response rate (30%, 50%, 90%, undetectable = 0.2 ng/mL), PSA at 6 months and 12 months after completion of radiotherapy and PSA ≥0.1 ng/mL at 6 months and 12 months after completion of radiotherapy","definition_or_measurement_approach":"Measures include time to PSA response/progression and PSA response rates (≥30%, ≥50%, ≥90%, undetectable = 0.2 ng/mL); PSA measured at 6 and 12 months post-radiotherapy; PSA ≥0.1 ng/mL at 6 and 12 months noted."}
• {"endpoint_text":"- Overall survival and Survival rates at 5 years. Overall survival is defined as the time from treatment initiation to the date of documented death from any cause.","definition_or_measurement_approach":"Overall survival: time from treatment initiation to documented death from any cause; 5-year survival rates measured."}
• {"endpoint_text":"- Cancer-specific survival and Cancer-specific survival rates. Cancer-specific survival is defined as the time from treatment initiation to the date of documented death from prostate cancer or complication from the treatment, whichever occurs first","definition_or_measurement_approach":"Cancer-specific survival: time from treatment initiation to death due to prostate cancer or treatment complication, whichever occurs first; rates measured."}
• {"endpoint_text":"- Time to pain progression (EVA scale)","definition_or_measurement_approach":"Time until pain progression as measured on the EVA (visual analogue) scale."}
• {"endpoint_text":"- Toxicities (CTCAE v5.0)","definition_or_measurement_approach":"Adverse events graded according to CTCAE v5.0."}
• {"endpoint_text":"- Quality of life ( EORTC QLQ-C302 and QLQ-PR253)","definition_or_measurement_approach":"Quality of life assessed using EORTC QLQ-C30 and QLQ-PR25 instruments."}

France

Earliest CTIS Part Ii Submission Date

17-10-2024

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

512

Number Of Sites

20

Number Of Participants

152

Primary sponsor

Full Name

ARTIC

Organisation Type

Patient organisation/association

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"Unicancer","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"France","full_name":"Exystat","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Eurofins BioPharma Product Testing Biologics","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}