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
About this trial
This is an interventional treatment trial for Prostate Cancer
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
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
NCT ID
NCT05116475
First Posted
October 27, 2021
Last Updated
February 10, 2022
Sponsor
Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
Collaborators
Bayer
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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