Metastatic Hormone-Sensitive Prostate Cancer
Conditions
Keywords
Prostatic Neoplasms, Hormone-Sensitive/Metastatic Prostate Cancer
Brief summary
This is an international, prospective, open-label, multicenter, multi-cohort, non-interventional observational study designed to describe the real-world effectiveness and safety of darolutamide in combination with androgen deprivation therapy (ADT), with or without docetaxel, in patients with metastatic hormone-sensitive prostate cancer (mHSPC). The study aims to enroll approximately 1,600 male patients (800 per cohort) from multiple countries, primarily in Europe, who have a diagnosis of mHSPC and for whom a decision to treat with darolutamide has been made by the treating physician prior to enrollment. The primary objective is to estimate the proportion of patients achieving undetectable prostate-specific antigen (PSA) levels (\<0.2 ng/mL) at 1 year of treatment in each cohort. Secondary objectives include describing patient demographics, clinical characteristics, prior and concomitant treatments, adverse events, and clinical effectiveness measures such as overall survival, time to new treatment, time to castration resistance, and time to PSA progression. Further objectives involve assessing quality of life, reasons for not adding docetaxel, outcomes by patient subgroups (e.g., Gleason score, disease volume, ECOG status), genomic testing results, and hospitalization rates. Data will be collected using electronic case report forms (eCRF) during routine clinical practice, with no additional diagnostic or monitoring procedures required beyond standard care. All patients must provide informed consent prior to participation. The study will comply with applicable regulatory requirements, including IEC/IRB approval in all participating countries. Statistical analyses will be descriptive and exploratory, with interim analyses planned after 200, 400, and 600 patients per cohort have completed at least 12 months of treatment or discontinued therapy. The study is expected to provide valuable insights into the real-world use of darolutamide in mHSPC, supporting clinical decision-making and enhancing understanding of treatment patterns, effectiveness, and safety in diverse patient populations.
Interventions
Darolutamide administered per local standard of care in combination with ADT.
DRUGADT
Androgen deprivation therapy administered per local standard of care.
DRUGDocetaxel
Docetaxel administered per local standard of care in combination with darolutamide and ADT for cohort 1.
Sponsors
Bayer
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male patient with a diagnosis of mHSPC * Male aged ≥18 years (or country's legal age of adulthood if \>18 years) * Histologically or cytologically confirmed adenocarcinoma of prostate; may have begun ADT (up to 120 days prior to enrollment) * Metastatic disease by conventional or new generation imaging * Decision to initiate treatment with darolutamide with or without docetaxel made prior to enrollment * Signed informed patient consent before start of data collection * Life expectancy of ≥3 months based on clinical judgment
Exclusion criteria
* Participation in an investigational program with interventions outside of routine clinical practice * Contraindications according to local marketing authorization * Any prior treatment with second-generation AR inhibitors (enzalutamide, apalutamide, or investigational AR inhibitors), CYP17 inhibitors (abiraterone acetate or investigational CYP17 inhibitors) as antineoplastic treatment for prostate cancer * Prior hormone therapy in the metastatic setting * Treatment with darolutamide initiated more than 7 days prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients in cohort 1 achieving undetectable PSA (<0.2 ng/mL) at 1 year | after 1 year of treatment | To describe the effectiveness of darolutamide + ADT + docetaxel in patients with mHSPC by means of estimating the prostate-specific antigen (PSA) undetectable rates (PSA\<0.2 ng/mL) after 1 year of study treatment. |
| Proportion of patients in cohort 2 achieving undetectable PSA (<0.2 ng/mL) at 1 year | after 1 year of treatment | To describe the effectiveness of darolutamide + ADT in patients with mHSPC by means of estimating the prostate-specific antigen (PSA) undetectable rates (PSA\<0.2 ng/mL) after 1 year of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival per cohort and per country | up to 4 years | Time from start of darolutamide treatment until death from any cause. |
| Overall survival per cohort in all countries | up to 4 years | Time from start of darolutamide treatment until death from any cause. |
| Time to subsequent treatment per cohort and per country | up to 4 years | Time from start of darolutamide treatment to initiation of a new anti-cancer therapy. |
| Time to subsequent treatment per cohort in all countries | up to 4 years | Time from start of darolutamide treatment to initiation of a new anti-cancer therapy. |
| Time to castration resistance (CRPC) per cohort and per country | up to 4 years | Time from enrollment until documented clinical or PSA progression with testosterone level \<50 ng/dL or documented medical/surgical castration. |
| Time to castration resistance (CRPC) per cohort in all countries | up to 4 years | Time from enrollment until documented clinical or PSA progression with testosterone level \<50 ng/dL or documented medical/surgical castration. |
| Time to PSA progression per cohort and per country | up to 4 years | Time from start of darolutamide treatment to PSA progression (≥25% increase above nadir and ≥2 ng/mL, confirmed by a second value ≥3 weeks later, but prior to 6 months, while on treatment). |
| Time to PSA progression per cohort in all countries | up to 4 years | Time from start of darolutamide treatment to PSA progression (≥25% increase above nadir and ≥2 ng/mL, confirmed by a second value ≥3 weeks later, but prior to 6 months, while on treatment). |
| PSA response rate per cohort and per country | 1 year | Proportion of patients with blood PSA level \<0.2 ng/mL, confirmed by a second subsequent PSA value \<0.2 ng/mL 3 or more weeks later |
| PSA response rate per cohort in all countries | 1 year | Proportion of patients with blood PSA level \<0.2 ng/mL, confirmed by a second subsequent PSA value \<0.2 ng/mL 3 or more weeks later |
| Survival rate per cohort and per country | up to 4 years | Survival rate at specified time points. |
| Survival rate per cohort and all countries | up to 4 years | Survival rate at specified time points. |
| Time to discontinuation per cohort and per country | up to 4 years | Time from start of darolutamide treatment to permanent discontinuation or death |
| Time to discontinuation per cohort in all countries | up to 4 years | Time from start of darolutamide treatment to permanent discontinuation or death |
| Reason for discontinuation percohort and per country | up to 4 years | Reason for permanent darolutamide discontinuation |
| Reason for discontinuation per cohort in all countries | up to 4 years | Reason for permanent darolutamide discontinuation |
| Patient demographics per cohort and per country | at baseline | Demographic characteristics at the first documented regular visit ion the study, referred to as baseline). |
| Patient demographics per cohort in all countries | at baseline | Demographic characteristics at the first documented regular visit ion the study, referred to as baseline). |
| Medical History per cohort and per country | at baseline | The medical history will be documented at study start. |
| Medical History per cohort in all countries | at baseline | The medical history will be documented at study start. |
| Concomitant medication per cohort and per country | up to 4 years | Documentation of Concomitant medication. |
| Concomitant medication per cohort in all countries | up to 4 years | Documentation of Concomitant medication. |
| Concomitant treatment per cohort and per country | up to 4 years | Documentation of Concomitant treatments. |
| Concomitant treatment per cohort in all countries | up to 4 years | Documentation of Concomitant treatments. |
| Darolutamide use per cohort and per country | up to 4 years | To describe real-world use of darolutamide in mHSPC patients. |
| Darolutamide use per cohort in all countries | up to 4 years | To describe real-world use of darolutamide in mHSPC patients. |
| Diagnostic Imaging Technology per cohort and per country | at baseline | Documentation of Diagnostic Imaging Technology at the initial study visits (baseline). |
| Diagnostic Imaging Technology per cohort in all countries | at baseline | Documentation of Diagnostic Imaging Technology at the initial study visits (baseline). |
| Adverse events per cohort and per country | up to 4 years | Number of all adverse events. |
| Adverse events per cohort in all countries | up to 4 years | Number of all adverse events. |
| Serious Adverse events per cohort and per country | up to 4 years | Number of all serious adverse events. |
| Serious Adverse events per cohort in all countries | up to 4 years | Number of all serious adverse events. |
| Drug-related Adverse events per cohort and per country | up to 4 years | Number of all drug-related (darolutamide) adverse events. |
| Drug-related Adverse events per cohort in all countries | up to 4 years | Number of all drug-related (darolutamide) adverse events. |
| Serious Drug-related Adverse events per cohort and per country | up to 4 years | Number of all serious drug-related (darolutamide) adverse events. |
| Serious Drug-related Adverse events per cohort in all countries | up to 4 years | Number of all serious drug-related (darolutamide) adverse events. |
| Adverse events leading to treatment discontinuation per cohort and per country | up to 4 years | Number of adverse events leading to treatment discontinuation. |
| Adverse events leading to treatment discontinuation per cohort in all countries | up to 4 years | Number of adverse events leading to treatment discontinuation. |
| Vital Signs: Blood Pressure per cohort and per country | up to 4 years | Blood Pressure is measured in mmHg throughout the study, at all major visit types, over the full observation period. |
| Vital Signs: Blood Pressure per cohort in all countries | up to 4 years | Blood Pressure is measured in mmHg throughout the study, at all major visit types, over the full observation period. |
| Vital Signs: Body Temperature per cohort and per country | up to 4 years | Body Temperature is measured in degrees Celsius (°C) or Fahrenheit (°F) (as per local practice) throughout the study, at all major visit types, over the full observation period. |
| Vital Signs: Body Temperature per cohort in all countries | up to 4 years | Body Temperature is measured in degrees Celsius (°C) or Fahrenheit (°F) (as per local practice) throughout the study, at all major visit types, over the full observation period. |
| Vital Signs: Weight per cohort and per country | up to 4 years | Weight is measured in kilograms (kg) throughout the study, at all major visit types, over the full observation period. |
| Vital Signs: Weight per cohort in all countries | up to 4 years | Weight is measured in kilograms (kg) throughout the study, at all major visit types, over the full observation period. |
| Vital Signs: Height per cohort and per country | up to 4 years | Height is measured in centimeters (cm) throughout the study, at all major visit types, over the full observation period. |
| Vital Signs: Height per cohort in all countries | up to 4 years | Height is measured in centimeters (cm) throughout the study, at all major visit types, over the full observation period. |
| Laboratory Parameters: Hematology (Hemoglobin) per cohort and per country | up to 4 years | Hemoglobin (g/dL)) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Hematology (Hemoglobin) per cohort in all countries | up to 4 years | Hemoglobin (g/dL)) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Hematology (WBC) per cohort and per country | up to 4 years | White Blood Cell Count (WBC) (x10\^9/L) is performed throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Hematology (WBC) per cohort in all countries | up to 4 years | White Blood Cell Count (WBC) (x10\^9/L) is performed throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Hematology (Platelet Count) per cohort and per country | up to 4 years | Platelet Count (x10\^9/L) is performed throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Hematology (Platelet Count) per cohort in all countries | up to 4 years | Platelet Count (x10\^9/L) is performed throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Clinical Chemistry (Creatinine) per cohort and per country | up to 4 years | Serum Creatinine (mg/dL or µmol/L) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Clinical Chemistry (Creatinine) per cohort in all countries | up to 4 years | Serum Creatinine (mg/dL or µmol/L) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Clinical Chemistry (ALT) per cohort and per country | up to 4 years | Alanine Aminotransferase (ALT) (U/L) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Clinical Chemistry (ALT) per cohort in all countries | up to 4 years | Alanine Aminotransferase (ALT) (U/L) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Clinical Chemistry (AST) per cohort and per country | up to 4 years | Aspartate Aminotransferase (AST) (U/L) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Clinical Chemistry (AST) per cohort in all countries | up to 4 years | Aspartate Aminotransferase (AST) (U/L) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Clinical Chemistry (Bilirubin) per cohort and per country | up to 4 years | Total Bilirubin (mg/dL or µmol/L) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Clinical Chemistry (Bilirubin) per cohort in all countries | up to 4 years | Total Bilirubin (mg/dL or µmol/L) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Clinical Chemistry (Alkaline Phosphatase) per cohort and per country | up to 4 years | Alkaline Phosphatase (U/L) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Clinical Chemistry (Alkaline Phosphatase) per cohort in all countries | up to 4 years | Alkaline Phosphatase (U/L) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Clinical Chemistry (PSA) per cohort and per country | up to 4 years | Prostate-Specific Antigen (PSA) (ng/mL) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
| Laboratory Parameters: Clinical Chemistry (PSA) per cohort in all countries | up to 4 years | Prostate-Specific Antigen (PSA) (ng/mL) is determined throughout the study, at all major visit types, for the duration of darolutamide treatment and as needed during follow-up, up to the end of observation. |
Countries
Belgium, Finland, France, Germany, Greece, Israel, Italy, Lithuania, Norway, Poland, Portugal, Saudi Arabia, Spain, Sweden, Switzerland, United Kingdom
Outcome results
None listed