High-risk, non-metastatic castration-resistant prostate cancer (MedDRA: hormonerefractory prostate cancer) MedDRA version: 21.1 Level: LLT Classification code 10066489 Term: Progression of prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and po
Conditions
Interventions
Product Name: Darolutamide
Product Code: BAY 1841788
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Darolutamide
CAS Number: 1297538-32-9
Current Sponsor code: BAY 1841788
Other descri
Sponsors
Bayer AG
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Written informed consent (IC) obtained. 2. Males aged = 18 years. 3. Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features. 4. CRPC is defined as 3 rising PSA levels after the nadir taken at least 1 week apart during ADT. If the patient has a history of antiandrogen use, the most recent PSA value must be obtained at least 4 weeks after antiandrogen withdrawal. See Section 6.1.1 of the Protocol for further details. 5. Castrate level of serum testosterone ( 2 ng/ml at screening.See Section 6.1.1 of the Protocol for further details. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 8. Blood counts at screening: haemoglobin = 9.0 g/dl, absolute neutrophil count = 1500/µl (1.5x10^9/l), platelet count = 100,000/µl (100x10^9/l ) (patient must not have received any growth factor or blood transfusion within 7 days of the haematology laboratory obtained at screening). 9. Screening values of serum alanine aminotransferase (ALT) and 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. 10. Sexually active patients, unless surgically sterile, must agree to use condoms as an effective barrier method and refrain from sperm donation during the study treatment and for 3 months after the end of the study treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1200
Exclusion criteria
Exclusion criteria: 1. History of metastatic disease at any time or presence of detectable metastases by blinded central reading within 42 days prior to start of study treatment. Presence of pelvic lymph nodes 2 years before randomisation. 7. Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days before randomisation. 8. Radiation therapy (external beam radiation therapy [EBRT], brachytherapy, or radiopharmaceuticals) within 12 weeks before randomisation. 9. Severe or uncontrolled concurrent disease, infection or co-morbidity that, in the opinion of the investigator, would make the patient inappropriate for enrolment. 10. Treatment with an osteoclast-targeted therapy (bisphosphonate or denosumab) to prevent skeletal-related events within 12 weeks before randomisation. Patients receiving osteoclast-targeted therapy to prevent bone loss at a dose and schedule indicated for osteoporosis may continue treatment at the same dose and schedule. 11. Known hypersensitivity to the study treatment or any of its ingredients. 12. Major surgery within 28 days before randomisation. 13. Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV. 14. Uncontrolled hypertension as indicated by a systolic BP >=160 mmHg or diastolic BP >=100 mmHg at screening. 15. 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 treatment has been completed >=5 years ago and from which the patient has been disease-free. 16. Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment. 17. Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease. 18. Treatment with any investigational drug within 28 days before randomisation. 19. Any condition that in the opinion of the investigator would impair the patients’ ability to comply with the study procedures. 20. Unable to swallow study medications and comply with study requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate the superiority of darolutamide vs. placebo in metastasis free survival (MFS) in patients with high-risk nmCRPC;Primary end point(s): The primary efficacy variable is metastasis free survival (MFS), defined as time between randomisation and evidence of metastasis or death from any cause, whichever occurs first;Timepoint(s) of evaluation of this end point: Will be evaluated at about 385 events;Secondary Objective: The secondary objectives of this study are to demonstrate the benefit of darolutamide for: Overal survival (OS), time to first symptomatic skeletal related event (SSE), time to initiation of first cytotoxic chemotherapy for prostate cancer, time to pain progression and to characterise the safety and tolerability of darolutamide | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival (OS) is defined as time from randomisation to date of death from any cause. Survival status will be assessed from randomisation until the end of follow-up period. Time to first Symptomatic Skeletal Event (SSE) is defined as time from randomisation to the first occurrence of SSE. SSE is defined as External Beam Radiation Therapy (EBRT) to relieve skeletal symptoms, new symptomatic pathologic bone fracture, or occurrence of spinal cord compression or tumour-related orthopaedic surgical intervention, whichever comes first. Time to cytotoxic chemotherapy is defined as time from randomisation to initiation of the first cytotoxic chemotherapy. Pain progression is defined as an increase of 2 points from baseline in question 3 of Brief Pain Inventory - Short Form (BPI-SF) (related to the worst pain in the last 24 hours) taken as a 7-day average, or initiation of short or long-acting opioids for pain, whichever comes first. ;Timepoint(s) of evaluation of this end point: Survival status will be assessed from randomisation until the end of follow-up period. SSE will be assessed from randomisation until the first occurrence of SSE. Use of cytotoxic chemotherapy will be assessed from randomisation until the first use of cytotoxic chemotherapy. Pain will be assessed with the BPI-SF questionnaire (Appendix 4), pain diary and opioid use from baseline until the end of follow-up period. | — |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, Colombia, Czech Republic, Estonia, Finland, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Peru, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactBayer Clini Trials Contact
Bayer AG
Outcome results
None listed