Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer

Study Overview
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Brief Summary
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The purpose of the study is to assess the efficacy and safety of darolutamide in combination with standard androgen deprivation therapy (ADT) in patients with metastatic hormone sensitive prostate cancer.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Darolutamide in Addition to Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Men With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: Darolutamide (Nubeqa, BAY1841788)
* Drug: Placebo
* Other: Androgen deprivation therapy (ADT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of prostate Metastatic disease Started ADT (LHRH agonist/antagonist or orchiectomy) with or without first generation anti-androgen, but not earlier than 12 weeks before randomization Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2 Adequate bone marrow, liver and renal function Exclusion Criteria: Prior treatment with: LHRH agonist/antagonists except neoadjuvant and /or adjuvant therapy; Second-generation androgen receptor (AR) inhibitors such as enzalutamide, darolutamide, apalutamide or other investigational AR inhibitors; Cytochrome P17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as anti-cancer treatment for prostate cancer; Chemotherapy including docetaxel or immunotherapy for prostate cancer; Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days prior to randomization; Radiopharmaceuticals; Any other anti-cancer treatment for prostate cancer, excluding local therapies and ADT. Treatment with radiotherapy within 2 weeks before randomization Contraindication to iodinated CT and gadolinium chelate MRI intravenous contrast agent(s) Had 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 Class III or IV) Uncontrolled hypertension as indicated by a resting systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical management A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of study drug Any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to randomization Inability to swallow oral medications

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Darolutamide+ADT<br>Participants will receive darolutamide 600 mg (2 tablets of 300 mg) twice daily with food and ADT of investigator's choice as standard therapy | Drug: Darolutamide (Nubeqa, BAY1841788)<br>* Coated tablet, oral administration<br>Other: Androgen deprivation therapy (ADT)<br>* Luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or orchiectomy<br>|
| Placebo Comparator: Placebo+ADT<br>Participants will receive placebo twice daily with food and ADT of investigator's choice as standard therapy | Drug: Placebo<br>* Coated tablet matching Darolutamide in appearance, oral administration<br>Other: Androgen deprivation therapy (ADT)<br>* Luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or orchiectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiological progression-free survival (rPFS) | Time from the date of randomization to the date of first documentation of radiological progressive disease or death due to any cause, whichever occurs first. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Time from the date of randomization to the date of death from any cause. | Up to 55 months | 
| Time to castration-resistant prostate cancer (CRPC) | Time from the date of randomization to the date of first castration resistant event (radiological progression, PSA progression or symptomatic skeletal events, whichever occurs first). | Up to 55 months | 
| Time to initiation of subsequent anti-cancer therapy | Time from the date of randomization to initiation of first subsequent anti-cancer therapy for prostate cancer. | Up to 55 months | 
| Time to PSA progression | Time from the date of randomization to the date of first prostate-specific antigen (PSA) progression. PSA progression is defined as a ≥25% increase above the nadir (lowest Screening or baseline) value, which is confirmed by a second value 3 or more weeks later, and an increase in absolute value of ≥ 2 ng/mL above nadir, at least 12 weeks from baseline. | Up to 55 months | 
| PSA undetectable rates (<0.2 ng/mL) | The percentage of participants with detectable PSA values (≥0.2 ng/mL) at baseline which become undetectable (<0.2 ng/mL) during the study treatment. | Up to 55 months | 
| Time to pain progression | Time from the date of randomization to pain progression, where progression is defined as an increase of 2 or more points from baseline. Pain to be assessed with a patient reported questionaire. | Up to 55 months | 
| Number of participants with adverse events as a measure of safety |  | Up to 55 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic hormone-sensitive prostate cancer