Metastatic Hormone-sensitive Prostate Cancer
Conditions
Keywords
Metastatic hormone-sensitive prostate cancer (mHSPC), Prostate Cancer, Darolutamide, Nubeqa
Brief summary
The purpose of the study is to assess if the addition of darolutamide to ADT compared with ADT alone would result in superior clinical efficacy in participants with metastatic hormone-sensitive prostate cancer (mHSPC) by progression-free survival. The researchers want to learn how long it takes for the cancer to get worse (also known as "progression-free survival") by either increasing symptoms, new metastases, PSA rise or death. All participants will be on treatment and take darolutamide with ADT until their cancer spreads, they have a medical problem, or they leave the study. The results will then be compared with patients' results from another study who received ADT alone (CHAARTED). This study will also assess safety by gathering adverse event information throughout the duration of the study. An adverse event is any medical problem, related or not to study treatment that a participant has during a study. The study drug, is already available for doctors to prescribe to patients with prostate cancer, including those with metastatic disease as well as those whose cancer has not yet spread to other parts of the body. The study drug, darolutamide, works by blocking a protein called a receptor from attaching to a hormone called androgen that is found in men. This protein can also be found in prostate cancer cells. ADT is a treatment that doctors are currently able to prescribe to patients with mHSPC. ADT is used to lower the amount of the androgen hormone. Darolutamide is approved for use with ADT, with or without docetaxel, in patients with mHSPC, and with ADT alone in non-metastatic castration-resistant prostate cancer (nmCRPC) in patients who are at high risk of developing metastatic disease.
Interventions
300 mg per tablet, oral administration with food
OTHERADT
LHRH agonist/antagonist or orchiectomy
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From start of treatment to the date when approximately 161 PFS events were observed across the ARASEC cohort and the matched controls, approximately 40 months | Time interval from enrollment to PSA progression, clinical progression or death, whichever occurs first. PSA progression is defined as when the PSA demonstrates an increase that is more than 50% of nadir, taking as reference the lowest recorded PSA level since starting androgen deprivation therapy (ADT). Clinical progression is defined as increasing symptomatic bone metastases, radiographic progression per Response Evaluation Criteria In Solid Tumors (RECIST) criteria (v. 1.1) for soft tissue metastases and PCWG3 criteria for bone metastases, or clinical deterioration due to cancer per investigator's opinion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From start of treatment to the date when approximately 161 PFS events were observed across the ARASEC cohort and the matched controls, approximately 40 months. | Time from the date of enrollment until death resulting from any cause or the date last known alive. |
| Radiographic Progression-free Survival (rPFS) | From start of treatment to the date when approximately 161 PFS events were observed across the ARASEC cohort and the matched controls, approximately 40 months. | Time from enrollment to investigator-assessed radiographic progression per Response Evaluation Criteria In Solid Tumors (RECIST) criteria (v. 1.1) for soft tissue metastases and PCWG3 criteria for bone metastases or death, whichever occurs first. |
| Time to Castration-resistant Prostate Cancer (CRPC) | From start of treatment to the date when approximately 161 PFS events were observed across the ARASEC cohort and the matched controls, approximately 40 months. | Time from enrollment until documented clinical or PSA progression with a testosterone level of less than 50 ng per deciliter or documented medical castration or surgical castration. |
| Undetectable PSA Response Rate | At 6 months after study drug first administration. | PSA level of less than 0.2 ng per milliliter on two consecutive measurements at least 4 weeks apart. |
| Number of Participants With Adverse Events | From start of study drug administration until 30 days after the last administration. | Adverse Events (AEs) were assessed by National Cancer Institute-Common Terminology Criteria (NCI CTCAE) v. 5.0. Treatment-emergent AE (TEAEs) is defined as any event any event arising or worsening after the first dose of study drug until 30 days after the last dose of study drug. |
Countries
United States
Participant flow
Recruitment details
Study was conducted between 04 Nov 2021 (first participant first visit) and 30 May 2025 (primary completion date).
Pre-assignment details
In total 293 participants were screened (signed the informed consent) and 70 were screen failures. Overall, 223 participants were assigned to treatment. Efficacy analyses used the ARASEC Match Full Analysis Set (M-FAS), which comprised 160 ARASEC participants who were matched 1:1 with participants from the CHAARTED ADT control arm (NCT00309985). Safety was assessed in both ARASEC populations (223 in Match-Eligible FAS; 160 in M-FAS).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 72.0 Years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 199 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 15 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 29 Participants |
| Race/Ethnicity, Customized Not Reported | 6 Participants |
| Race/Ethnicity, Customized White | 181 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 223 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 22 / 160 | 26 / 223 |
| other Total, other adverse events | 137 / 160 | 196 / 223 |
| serious Total, serious adverse events | 39 / 160 | 52 / 223 |
Outcome results
None listed