Evaluation of dAroLutamide Addition to anDrogen Deprivation Therapy and radIatioN Therapy in Newly Diagnosed Prostate Cancer With Pelvic Lymph Nodes Metastases

NCT05116475 | Recruiting Phase 3 DMC

• 1 other identifier: ALADDIN
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

Prospective, multicenter, comparative, randomized placebo-controlled Phase III trial - patients with hormone-naïve prostate cancer and pelvic lymph nodes metastases

Conditions

Prostate Cancer

Keywords

Prostate cancer; Darolutamide; ARTIC; Bayer

Outcome Measures

Primary Outcomes (1)

• Failure-free survival FFS

  The failure-free survival is defined as the time from the date of randomization to clinical (new cancer-related symptoms), biochemical (PSA rising) or radiological (local relapse or new metastases) progression, death, end of 3-year follow-up period or lost to follow-up, whichever occurs first.

  3 years

Secondary Outcomes (10)

• Metastasis-free survival rates

  3 years

• Progression free survival rate

  3 years

• PSA response levels

  3 years

• Overall survival rates

  3 years

• Cancer-specific survival rates

  3 years

Study Arms (2)

Arm A

EXPERIMENTAL

Arm A: ADT + Intensity-Modulated Image-Guided Radiation Therapy + Darolutamide ADT will be associated with LHRH agonists or antagonists for 24 months4. Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months.

Drug: Darolutamide 300 mg

Arm B

PLACEBO COMPARATOR

Arm B: ADT + Intensity-Modulated Image-Guided Radiation Therapy + Placebo of Darolutamide ADT will be associated with LHRH agonists or antagonists for 24 months4. Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months.

Drug: Placebo of Darolutamide

Interventions

Darolutamide 300 mg DRUG

Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months.

Arm A

Placebo of Darolutamide DRUG

Placebo of Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months.

Arm B

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed, histologically confirmed prostate adenocarcinoma
• ≥ 18 years old.
• Initial staging with Pelvic MRI, body CT-scan/bone scan or Choline or PSMA PET-CT
• Any T stage
• N stage: N1 - Pelvis lymph nodes metastases (upper limit defined as the L4/L5 interspace).
• Intention to treat with long-term androgen deprivation therapy (24 months).
• Hormonal therapy with LH-RH agonist or antagonist is allowed up to 3months prior to randomization.
• Able to receive protocol therapy and have life expectancy of at least 36 months, ECOG Performance Status (PS) 0-2.
• 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).
• 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.
• 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.
• Written informed consent.
• Willing and expected to comply with follow-up schedule.
• Affiliated to the social security system.
• Use of 5-α reductase inhibitors (finasteride, dutasteride) is allowed

You may not qualify if:

• Lymph nodes metastases outside of the pelvis
• Bone or visceral metastases
• Prior systemic therapy for locally-advanced prostate cancer except for LH-RH agonist or antagonist up to 3 months before randomization
• 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, flutamide, nilutamide, cyproterone acetate)
• Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days before randomization.
• Patients with QTor QTc interval \> 450 ms on the ECG
• Initiation of treatment with bisphosphonate or denosumab within 12 weeks before randomization. Patients receiving bone loss prevention treatment on a stable dose of e.g. bisphosphonate or denosumab for at least 28 days before randomization can continue the treatment during the study.
• Known hypersensitivity to the study treatment (RT, ADT, darolutamide/placebo) or any of its ingredients.
• Major surgery within 28 days before randomization.
• Any of the following within 6 months before randomization: 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.
• 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.

Sponsors & Collaborators

• Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie: lead
• Bayer: collaborator

Study Sites (1)

Pôle Santé Léonard de Vinci

Chambray-lès-Tours, 37170, France

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

darolutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Pierre COMBE, MD

  Centre Oncologie Radiothérapie 37 - CORT37

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ishak Senouci

CONTACT

0766185461; ishak.senouci@association-artic.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: placebo-controlled trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2021
• First Posted: November 11, 2021
• Study Start: August 30, 2022
• Primary Completion: February 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)