A Study to Learn How Well Darolutamide Administered Together With Androgen Deprivation Therapy (ADT) Works in Men With Metastatic Hormone-sensitive Prostate Cancer. Results Will be Compared With ADT Alone From a Previously Conducted Study.
Age: 18 years - 66+
Healthy Subjects: No
Study Phase: Phase 2
Recruitment Status: Recruiting
Start Date: November 29, 2021
End Date: June 22, 2026
- Histologically or cytologically confirmed adenocarcinoma of prostate. Participants may have begun androgen-deprivation therapy (up to 120 days prior to enrollment). Note: Relugolix is not permitted as ADT in this study.
- Metastatic disease and will be stratified by presence of high volume or low volume disease.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2
- Adequate bone marrow, liver and renal function within 4 weeks of enrollment
- At least 4 weeks since prior major surgery and recovered from all toxicity from such surgery prior to enrollment
- Prior adjuvant or neoadjuvant hormonal therapy allowed provided the following criteria are met:
- Therapy was discontinued ≥ 12 months ago AND there was a clinical state without evidence of disease at least 12 months after completing adjuvant or neoadjuvant hormonal therapy, as defined by 1 of the following:
- PSA < 0.1 ng/mL after prostatectomy plus hormonal therapy
- PSA < 0.5 ng/mL and has not doubled above nadir after radiotherapy plus hormonal therapy
- Therapy lasted no more than 24 months
- Prior palliative radiotherapy allowed for participants, if commenced within 30 days before starting androgen deprivation.
- Bicalutamide, nilutamide or flutamide are allowed as single-agent therapy ≤ 28 days before medical castration to prevent flare.
- PSA met criteria for PSA progression
- History of malignancy in the past 5 years, with the exception of basal cell and squamous cell carcinoma of the skin.
- Had any of the following within 6 months before randomization: myocardial infarction, severe/unstable angina pectoris, congestive heart failure, hospitalization for any cardiac event, including conduction abnormalities
- Pathological finding consistent with small cell, or neuroendocrine carcinoma of the prostate
- Known brain/ leptomeningeal metastases
- An active viral hepatitis (defined as Hepatitis B surface antigen [HBsAg] reactive or detectable [qualitative] HBV DNA defined as HCV Ribonucleic Acid [RNA] [qualitative] is detected), known human immunodeficiency virus infection with detectable viral load, or chronic liver disease with a need of treatment
- 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 other serious or unstable illness, or medical, social, or psychological condition, that could jeopardize the safety of the participant and/or his compliance with study procedures or may interfere with the participant's participation in the study or evaluation of the study results.
- Prior hormone therapy in the metastatic setting
- Prior chemotherapy in the adjuvant or neoadjuvant setting
- Concurrent use or previous exposure of 5-alpha reductase inhibitors (within 28 days before the start of darolutamide or 5 half-lives of the drug, whichever is longer)
- Any Prior treatment with second-generation androgen receptor (AR) inhibitors such as enzalutamide, apalutamide, darolutamide, or other investigational AR inhibitors, Cytochrome P17 enzyme inhibitor such as abiraterone acetate or other investigational CYP 17 as antineoplastic treatment for prostate cancer
- Previous (within 28 days before the start of darolutamide or 5 half-lives of the investigational treatment of the previous study, whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s).
- Contraindication to both CT and MRI contrast agent
- Hypersensitivity to any of the study treatments, study treatment classes, or excipients in the formulation of the study treatments
- Inability to swallow oral medications