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

Phase 3

Not yet recruiting

• Conditions: Newly diagnosed prostate cancer with pelvic lymph nodes metastases

• Registration Number: 2024-517285-41-00
• Lead Sponsor: ARTIC

Brief Summary

Evaluate the impact of darolutamide in addition to ADT and Radiotherapy on the failurefree survival (FFS) in patients with hormone-naïve prostate cancer and pelvic lymph nodes metastases

Detailed Description

Standard of care for patients with prostate cancer (PC) with pelvic lymph nodes metastases is radiotherapy (RT) with long-term androgen deprivation therapy (ADT). . Darolutamide improves survival in men with castration-refractory non metastatic prostate cancer. We hypothesize that adding Darolutamide to ADT and RT could improve FFS for these high-risk patients.

Study Timeline

• Study First Posted: 2024-11-05
• Last Update Posted: 2024-12-24

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Male
• Target Recruitment: 152

Inclusion Criteria

1. Newly diagnosed, histologically confirmed prostate adenocarcinoma

2. 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.

3. 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.

4. Written informed consent.

5. Willing and expected to comply with follow-up schedule.

6. Affiliated to the social security system.

7. Use of 5-α reductase inhibitors (finasteride, dutasteride) is allowed

8. ≥ 18 years old.

9. Initial staging with Pelvic MRI + (contrast-enhanced body CT-scan + bone scan or Choline or PSMA PET-CT)

10. Any T stage

11. N stage: N1 - Pelvis lymph nodes metastases (upper limit defined as the L4/L5 interspace).

12. Intention to treat with long-term androgen deprivation therapy (24 months).

13. Hormonal therapy with LHRH agonist or antagonist is allowed up to 3 months prior to treatment initiation

14. Able to receive protocol therapy and have life expectancy of at least 36 months, ECOG Performance Status (PS) 0-2.

15. 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

1. Lymph nodes metastases outside of the pelvis

2. 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.

3. 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.

4. 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.

5. Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment.

6. Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease.

7. Participation in another interventional clinical trial and any concurrent treatment with any investigational drug

8. Any condition that in the opinion of the investigator would impair the patients’ ability to comply with the study procedures.

9. Unable to swallow study medications and comply with study requirements

10. Galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption

11. History of bilateral hip replacements making IMRT impossible

12. Bone or visceral metastases

13. Contra-indications for the administration of any of the study treatments (RT, ADT, darolutamide/placebo) or any of its ingredients.

14. Patient under guardianship, administrative curatorship and not able to give informed consent

15. Prior systemic therapy for locally-advanced prostate cancer except for LHRH agonist or antagonist up to 3 months before treatment initiation

16. 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.

17. Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days before treatment initiation

18. Patients with QTor QTc interval > 450 ms on the ECG

19. 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.

20. Known hypersensitivity to the study treatment (RT, ADT, darolutamide/placebo) or any of its ingredients.

21. Major surgery within 28 days before treatment initiation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.		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.

Secondary Outcome Measures

Name	Time	Method
• Failure-free survival rates at 3 years.		• 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.		• 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.		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.		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.
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.		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		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)		Time to pain progression (EVA scale)
Toxicities (CTCAE v5.0)		Toxicities (CTCAE v5.0)
Quality of life ( EORTC QLQ-C302 and QLQ-PR253)		Quality of life ( EORTC QLQ-C302 and QLQ-PR253)

Trial Locations

Locations (19)

Georges-Pompidou European Hospital; 🇫🇷 Paris, France

Institut Bergonie; 🇫🇷 Bordeaux, France

Centre D'Oncologie Et De Radiotherapie 37; 🇫🇷 Chambray-Les-Tours, France

CHRU Brest site hôpital MORVAN; 🇫🇷 Brest, France

CHU Grenoble Alpes - Hôpital Michallon; 🇫🇷 La Tronche, France

CHU Toulouse; 🇫🇷 Toulouse, France

Centre Jean BERNARD; 🇫🇷 Le Mans, France

Centre de Cancérologie Les Dentellières; 🇫🇷 France

Centre Georges François Leclerc; 🇫🇷 Dijon, France

Institut De Cancerologie De L Ouest; 🇫🇷 Angers, France

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Georges-Pompidou European Hospital

🇫🇷Paris, France

Bibault Jean Emmanuel

Site contact

0156093447

jean-emmanuel.bibault@aphp.fr