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

Primary Purpose

Prostate Cancer

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Darolutamide 300 mg
Placebo of Darolutamide
Sponsored by
Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Newly diagnosed, histologically confirmed prostate adenocarcinoma
  2. ≥ 18 years old.
  3. Initial staging with Pelvic MRI, CT-scan and or Choline or PSMA PET-CT
  4. Any T stage
  5. 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 LH-RH agonist or antagonist is allowed up to 2-months prior to randomization.
  8. Able to receive either protocol therapy and 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).
  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. 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. Written informed consent.
  13. Willing and expected to comply with follow-up schedule.
  14. Affiliated to the social security system.

Exclusion Criteria:

  1. Lymph nodes metastases outside of the pelvis
  2. Bone or visceral metastases
  3. Prior systemic therapy for locally-advanced prostate cancer.
  4. Prior treatment with:

    • Second generation AR inhibitors such as enzalutamide, ARN-509, ODM-201, other investigational AR inhibitors,
    • CYP17 enzyme inhibitor such as abiraterone acetate, TAK-700 or
    • Oral ketoconazole longer than for 28 days.
    • Use of estrogens, 5-α reductase inhibitors (finasteride, dutasteride) or AR inhibitors (bicalutamide, flutamide, nilutamide, cyproterone acetate) within 28 days before randomization.
  5. Prior chemotherapy or immunotherapy for prostate cancer, except adjuvant/neoadjuvant treatment, completed > 2 years before randomization.
  6. Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days before randomization.
  7. Severe or uncontrolled concurrent disease, infection or co-morbidity that, in the opinion of the investigator, would make the patient inappropriate for enrolment.
  8. 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.
  9. Known hypersensitivity to the study treatment (RT, ADT, darolutamide/placebo) or any of its ingredients.
  10. Major surgery within 28 days before randomization.
  11. 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.
  12. 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.
  13. 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.
  14. Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment.
  15. Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease.
  16. Participation in another interventional clinical trial and any concurrent treatment with any investigational drug within 28 days before randomization.
  17. Any condition that in the opinion of the investigator would impair the patients' ability to comply with the study procedures.
  18. Unable to swallow study medications and comply with study requirements.
  19. Galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
  20. History of bilateral hip replacements making IMRT impossible
  21. Contra-indications for the administration of any of the study treatments (RT, ADT, Darolutamide/placebo) or any of its ingredients.
  22. Patient under guardianship, administrative tutorship and incapable to give informed consent

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Arm A

    Arm B

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    Metastasis-free survival rates
    To evaluate the metastasis-free survival rates
    PSA response levels
    PSA response is defined by the rate of patients having a decrease of > 50% of their PSA level, as measured every 3 months from the date of randomization to the date of a documented biochemical relapse.
    Overall survival rates
    Overall survival is defined as the time from the date of randomization to the date of documented death from any cause, end of 3-year follow-up period or lost to follow-up, whichever occurs first
    Cancer-specific survival rates
    Cancer-specific survival is defined as the time from the date of randomization to the date of documented death from prostate cancer or complication from the treatment, end of 3-year follow-up period or lost to follow-up, whichever occurs first
    Time to pain progression
    Time to pain progression is defined as the time from the date of randomization to the date of documented pain, end of 3-year follow-up period or lost to follow-up, whichever occurs first
    Toxicities
    To evaluate toxicities (CTCAE v5.0) due to treatements
    Quality of life of the patient
    Quality of life will be assessed using self-administered questionnaires (EORTC QLQ-C302)
    Quality of life of the participants
    Quality of life will be assessed using self-administered questionnaires (EORTC QLQ-PR253) by patients

    Full Information

    First Posted
    October 27, 2021
    Last Updated
    February 10, 2022
    Sponsor
    Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
    Collaborators
    Bayer
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05116475
    Brief Title
    Evaluation of dAroLutamide Addition to anDrogen Deprivation Therapy and radIatioN Therapy in Newly Diagnosed Prostate Cancer With Pelvic Lymph Nodes Metastases
    Acronym
    ALADDIN
    Official Title
    Evaluation of dAroLutamide Addition to anDrogen Deprivation Therapy and radIatioN Therapy in Newly Diagnosed Prostate Cancer With Pelvic Lymph Nodes Metastases
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    April 2022 (Anticipated)
    Primary Completion Date
    February 2026 (Anticipated)
    Study Completion Date
    February 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
    Collaborators
    Bayer

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Prospective, multicenter, comparative, randomized placebo-controlled Phase III trial - 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Prostate Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Masking Description
    placebo-controlled trial
    Allocation
    Randomized
    Enrollment
    152 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm A
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Arm B
    Arm Type
    Placebo Comparator
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Darolutamide 300 mg
    Intervention Description
    Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo of Darolutamide
    Intervention Description
    Placebo of Darolutamide regimen will be of 2 tablets of 300 mg orally twice daily for 24 months.
    Primary Outcome Measure Information:
    Title
    Failure-free survival FFS
    Description
    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.
    Time Frame
    3 years
    Secondary Outcome Measure Information:
    Title
    Metastasis-free survival rates
    Description
    To evaluate the metastasis-free survival rates
    Time Frame
    3 years
    Title
    PSA response levels
    Description
    PSA response is defined by the rate of patients having a decrease of > 50% of their PSA level, as measured every 3 months from the date of randomization to the date of a documented biochemical relapse.
    Time Frame
    3 years
    Title
    Overall survival rates
    Description
    Overall survival is defined as the time from the date of randomization to the date of documented death from any cause, end of 3-year follow-up period or lost to follow-up, whichever occurs first
    Time Frame
    3 years
    Title
    Cancer-specific survival rates
    Description
    Cancer-specific survival is defined as the time from the date of randomization to the date of documented death from prostate cancer or complication from the treatment, end of 3-year follow-up period or lost to follow-up, whichever occurs first
    Time Frame
    3 years
    Title
    Time to pain progression
    Description
    Time to pain progression is defined as the time from the date of randomization to the date of documented pain, end of 3-year follow-up period or lost to follow-up, whichever occurs first
    Time Frame
    3 years
    Title
    Toxicities
    Description
    To evaluate toxicities (CTCAE v5.0) due to treatements
    Time Frame
    3 years
    Title
    Quality of life of the patient
    Description
    Quality of life will be assessed using self-administered questionnaires (EORTC QLQ-C302)
    Time Frame
    3 years
    Title
    Quality of life of the participants
    Description
    Quality of life will be assessed using self-administered questionnaires (EORTC QLQ-PR253) by patients
    Time Frame
    3 years

    10. Eligibility

    Sex
    Male
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    120 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Newly diagnosed, histologically confirmed prostate adenocarcinoma ≥ 18 years old. Initial staging with Pelvic MRI, CT-scan and or Choline or PSMA PET-CT Any T stage 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 2-months prior to randomization. Able to receive either protocol therapy and 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. Exclusion Criteria: Lymph nodes metastases outside of the pelvis Bone or visceral metastases Prior systemic therapy for locally-advanced prostate cancer. Prior treatment with: Second generation AR inhibitors such as enzalutamide, ARN-509, ODM-201, other investigational AR inhibitors, CYP17 enzyme inhibitor such as abiraterone acetate, TAK-700 or Oral ketoconazole longer than for 28 days. Use of estrogens, 5-α reductase inhibitors (finasteride, dutasteride) or AR inhibitors (bicalutamide, flutamide, nilutamide, cyproterone acetate) within 28 days before randomization. Prior chemotherapy or immunotherapy for prostate cancer, except adjuvant/neoadjuvant treatment, completed > 2 years before randomization. Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days before randomization. Severe or uncontrolled concurrent disease, infection or co-morbidity that, in the opinion of the investigator, would make the patient inappropriate for enrolment. 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. 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. Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment. Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease. Participation in another interventional clinical trial and any concurrent treatment with any investigational drug within 28 days before randomization. Any condition that in the opinion of the investigator would impair the patients' ability to comply with the study procedures. Unable to swallow study medications and comply with study requirements. Galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption History of bilateral hip replacements making IMRT impossible Contra-indications for the administration of any of the study treatments (RT, ADT, Darolutamide/placebo) or any of its ingredients. Patient under guardianship, administrative tutorship and incapable to give informed consent
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Mouna ROUABAH
    Phone
    01 56 09 50 16
    Email
    mouna.rouabah-ext@aphp.fr
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Pierre COMBE, MD
    Organizational Affiliation
    Centre Oncologie Radiothérapie 37 - CORT37
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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

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