Prospective, multicenter, comparative, randomized placebo-controlled Phase III trial evaluating dAroLutamide Addition to anDrogen Deprivation therapy and radIatioN therapy in newly diagnosed prostate cancer with pelvic lymph nodes metastases.

Evaluation of dAroLutamide Addition to anDrogen Deprivation therapy and radIatioN therapy in newly diagnosed prostate cancer with pelvic lymph nodes metastases - ALADDIN

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-003542-21-FR

Enrollment

152

Registered

2024-09-19

Start date

2022-02-28

Completion date

Unknown

Last updated

2024-11-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prostate cancer with pelvic lymph nodes metastases.

Interventions

Trade Name: NUBEQA Product Name: DAROLUTAMIDE Product Code: NUBEQA Pharmaceutical Form: Film-coated tablet Pharmaceutical form of the placebo: Film-coated tablet Route of administration of the placebo

Eligibility

Sex/Gender

Male

Inclusion criteria

Inclusion criteria: 1. Newly diagnosed, histologically confirmed prostate adenocarcinoma 2. = 18 years old. 3. Initial staging with Pelvic MRI + (contrast-enhanced body CT-scan + bone scan or Choline or PSMA PET-CT) 4. Any T stage 5. N stage: N1 - Pelvis lymph nodes metastases (upper limit defined as the L4/L5 interspace). 6. Intention to treat with long-term androgen deprivation therapy (24 months). 7. Hormonal therapy with LHRH agonist or antagonist is allowed up to 3 months prior to treatment initiation. 8. Able to receive protocol therapy and have life expectancy of at least 36 months, ECOG Performance Status (PS) 0-2. 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). ARTIC - Clinical Study Protocol ALADDIN GETUG P17 Edition Number 4.0 Date June 13th, 2024 9/44 RESTRICTED 10. Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) =65 years) yes F.1.3.1 Number of subjects for this age range 76

Exclusion criteria

Exclusion criteria: 1. Lymph nodes metastases outside of the pelvis 2. Bone or visceral metastases 3. Prior systemic therapy for locally-advanced prostate cancer except for LHRH agonist or antagonist up to 3 months before treatment initiation 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. 5. Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days before treatment initiation. 6. Patients with QTor QTc interval > 450 ms on the ECG 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. 8. Known hypersensitivity to the study treatment (RT, ADT, darolutamide/placebo) or any of its ingredients. 9. Major surgery within 28 days before treatment initiation. 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. 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. 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. 13. Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment. 14. Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease. 15. Participation in another interventional clinical trial and any concurrent treatment with any investigational drug 16. Any condition that in the opinion of the investigator would impair the patients’ ability to comply with the study procedures. 17. Unable to swallow study medications and comply with study requirements. 18. Galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption 19. History of bilateral hip replacements making IMRT impossible 20. Contra-indications for the administration of any of the study treatments (RT, ADT, darolutamide/placebo) or any of its ingredients. 21. Patient under guardianship, administrative curatorship and not able to give informed consent

Design outcomes

Primary

Measure	Time frame
Main Objective: Evaluate the impact of Darolutamide in addition to ADT and Radiotherapy on the failure-free survival (FFS) in patients with hormone-naïve prostate cancer and pelvic lymph nodes metastases.;Secondary Objective: Evaluate: 1.Failure-free survival rates at 3 years 2.Metastasis-free survival and Metastasis-free survival rates at 3 years 3.Progression-free survival and Progression-free survival rates at 3 years 4.Time to PSA response, Time to PSA progression and PSA response rate (30%, 50%, 90%, undetectable = 0.2 ng/mL), PSA at 6 months after completion of radiotherapy and PSA =0.1 ng/mL at 6 months after completion of radiotherapy 5.Overall survival and Survival rates at 3 years 6.Cancer-specific survival and Cancer-specific survival rates 7.Time to pain progression (EVA scale) 8.Toxicities (CTCAE v5.0) 9.Quality of life ( EORTC QLQ-C302 and QLQ-PR25) ;Primary end point(s): 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 3-year follow-up period or lost to follow-up, whichever occurs first.;Timepoint(s) of evaluation of this end point: Medical visit every 3 months for the first year and then every 6 months until the end of the trial. Blood samples (laboratory safety assessments) wil be taken before each visit = controling PSA level CT scan+ bone scan every 3 months the first year and every 6 months until the end of study.	—

Measure

Time frame

Main Objective: Evaluate the impact of Darolutamide in addition to ADT and Radiotherapy on the failure-free survival (FFS) in patients with hormone-naïve prostate cancer and pelvic lymph nodes metastases.;Secondary Objective: Evaluate: 1.Failure-free survival rates at 3 years 2.Metastasis-free survival and Metastasis-free survival rates at 3 years 3.Progression-free survival and Progression-free survival rates at 3 years 4.Time to PSA response, Time to PSA progression and PSA response rate (30%, 50%, 90%, undetectable = 0.2 ng/mL), PSA at 6 months after completion of radiotherapy and PSA =0.1 ng/mL at 6 months after completion of radiotherapy 5.Overall survival and Survival rates at 3 years 6.Cancer-specific survival and Cancer-specific survival rates 7.Time to pain progression (EVA scale) 8.Toxicities (CTCAE v5.0) 9.Quality of life ( EORTC QLQ-C302 and QLQ-PR25) ;Primary end point(s): 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 3-year follow-up period or lost to follow-up, whichever occurs first.;Timepoint(s) of evaluation of this end point: Medical visit every 3 months for the first year and then every 6 months until the end of the trial. Blood samples (laboratory safety assessments) wil be taken before each visit = controling PSA level CT scan+ bone scan every 3 months the first year and every 6 months until the end of study.

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Secondary

Measure	Time frame
Secondary end point(s): Failure-free survival rates at 3 years. • Metastasis-free survival and Metastasis-free survival rates at 3 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. • Progression-free survival and Progression-free survival rates at 3 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. • Time to PSA response, Time to PSA progression defined as the time from baseline to the date of biochemical relapse as defined by the Phoenix criteria (increase of 2 ng/mL from nadir). PSA response rate (30%, 50%, 90%, undetectable = 0.2 ng/mL). PSA response is defined by the rate of patients having a decrease of > 30%, 50%, 90% or undetectable (0.2ng/mL) of their PSA level from baseline, as measured every 3 months. PSA at 6 months after completion of radiotherapy and PSA =0.1 ng/mL at 6 months after completion of radiotherapy. • Overall survival and Survival rates at 3 years. Overall survival is defined as the time from treatment initiation to the date of documented death from any cause. • 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. • Time to pain progression (EVA scale) • Toxicities (CTCAE v5.0) • Quality of life ( EORTC QLQ-C302 and QLQ-PR253) ;Timepoint(s) of evaluation of this end point: CT scan+ bone scan every 3 months the first year and every 6 months until the end of study. Blood samples (laboratory safety assessments) wil be taken before each visit = controling PSA level Time t	—

Measure

Time frame

Secondary end point(s): Failure-free survival rates at 3 years. • Metastasis-free survival and Metastasis-free survival rates at 3 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. • Progression-free survival and Progression-free survival rates at 3 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. • Time to PSA response, Time to PSA progression defined as the time from baseline to the date of biochemical relapse as defined by the Phoenix criteria (increase of 2 ng/mL from nadir). PSA response rate (30%, 50%, 90%, undetectable = 0.2 ng/mL). PSA response is defined by the rate of patients having a decrease of > 30%, 50%, 90% or undetectable (0.2ng/mL) of their PSA level from baseline, as measured every 3 months. PSA at 6 months after completion of radiotherapy and PSA =0.1 ng/mL at 6 months after completion of radiotherapy. • Overall survival and Survival rates at 3 years. Overall survival is defined as the time from treatment initiation to the date of documented death from any cause. • 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. • Time to pain progression (EVA scale) • Toxicities (CTCAE v5.0) • Quality of life ( EORTC QLQ-C302 and QLQ-PR253) ;Timepoint(s) of evaluation of this end point: CT scan+ bone scan every 3 months the first year and every 6 months until the end of study. Blood samples (laboratory safety assessments) wil be taken before each visit = controling PSA level Time t

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Countries

France

Contacts

Public ContactSponsor

ARTIC - Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie

mouna.rouabah-ext@aphp.fr+330156 09 50 16

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026