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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Artic

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Decision date (initial)

2024-11-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bayer

External identifiers

EU CT number

2024-517285-41-00

EudraCT number

2021-003542-21

ClinicalTrials.gov

NCT05116475

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

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

Secondary objectives 9

1. 1. Failure-free survival rates at 5 years
2. 2. Metastasis-free survival and Metastasis-free survival rates at 5 years
3. 3. Progression-free survival and Progression-free survival rates at 5 years
4. 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 and 12 months after completion of radiotherapy and PSA ≥0.1 ng/mL at 6 months and 12 months after completion of radiotherapy
5. 5. Overall survival and Survival rates at 5 years
6. 6. Cancer-specific survival and Cancer-specific survival rates
7. 7. Time to pain progression (EVA scale)
8. 8. Toxicities (CTCAE v5.0)
9. 9. Quality of life ( EORTC QLQ-C302 and QLQ-PR253 )

Conditions and MedDRA coding

Newly diagnosed prostate cancer with pelvic lymph nodes metastases

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 1. Newly diagnosed, histologically confirmed prostate adenocarcinoma
2. 2. ≥ 18 years old.
3. 3. Initial staging with Pelvic MRI + (contrast-enhanced body CT-scan + bone scan or Choline or PSMA PET-CT)
4. 4. Any T stage
5. 5. N stage: N1 - Pelvis lymph nodes metastases (upper limit defined as the L4/L5 interspace).
6. 6. Intention to treat with long-term androgen deprivation therapy (24 months).
7. 7. Hormonal therapy with LHRH agonist or antagonist is allowed up to 3 months prior to treatment initiation
8. 8. Able to receive protocol therapy and have life expectancy of at least 36 months, ECOG Performance Status (PS) 0-2.
9. 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).
10. 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.
11. 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.
12. 12. Written informed consent.
13. 13. Willing and expected to comply with follow-up schedule.
14. 14. Affiliated to the social security system.
15. 15. Use of 5-α reductase inhibitors (finasteride, dutasteride) is allowed

Exclusion criteria 21

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 9

1. • Failure-free survival rates at 5 years.
2. • 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.
3. 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.
4. 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 and 12 months after completion of radiotherapy and PSA ≥0.1 ng/mL at 6 months and 12 months after completion of radiotherapy
5. 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.
6. 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
7. Time to pain progression (EVA scale)
8. Toxicities (CTCAE v5.0)
9. Quality of life ( EORTC QLQ-C302 and QLQ-PR253)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Artic

Sponsor organisation

ARTIC

Address

20 Rue Leblanc

City

Paris

Postcode

75015

Country

France

Scientific contact point

Organisation

Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie

Contact name

Scientific coordinator

Public contact point

Organisation

Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie

Contact name

Scientific coordinator

Third parties 3

Locations

1 EU/EEA country · 20 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications