A Single-arm, Open-label Phase 4 Study of Darolutamide in Addition to Standard Androgen Deprivation Therapy for Participants in India With High-risk Non-metastatic Castration-resistant Prostate Cancer (nmCRPC)
Overview
- Phase
- Phase 4
- Intervention
- Darolutamide (Nubeqa, BAY1841788)
- Conditions
- Non-metastatic Castration-resistant Prostate Cancer
- Sponsor
- Bayer
- Enrollment
- 50
- Locations
- 48
- Primary Endpoint
- Number of participants with adverse events (AEs) and serious adverse events (SAEs) and their severity.
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
Researchers are looking for a better way to treat men who have non-metastatic castration-resistant prostate cancer (nmCRPC). This is a type of cancer of the prostate that has not yet spread to other parts of the body and that keeps progressing even when the amount of male sex hormones like testosterone (also called androgens) is reduced to very low levels. To reduce androgen levels in prostate cancer patients, androgen deprivation therapy (ADT) is often used. As androgens stimulate the growth of prostate cancer cells, low levels are needed to reduce or slow the growth of these tumors.
In men with nmCRPC, the cancer worsens despite low testosterone levels (also called castration resistant).
Prostate-specific antigen (PSA) is a protein that is made by both normal cells and by cancerous cells in the body. Thus, PSA levels can be taken as a marker for prostate cancer development.
Men with nmCRPC usually have higher levels of (PSA) than normal. They are considered "high risk" if they show signs of quickly increasing PSA levels as this could mean that the tumor is growing and might spread to other parts of the body.
The study treatment darolutamide is already available in certain countries for doctors to prescribe to men with prostate cancer that has not yet spread to other parts of the body. It works by blocking androgens from attaching to proteins in cancer cells in the prostate.
Results of a previous study in men with high-risk nmCRPC who received darolutamide in addition to ADT are already available, but this study had no Indian patients and was not conducted in India.
Therefore, the main purpose of this study is to learn how safe darolutamide is when taken in addition to ADT in Indian participants with high-risk nmCRPC.
To answer this question, the researchers will collect all medical problems the participants have that arise during the study and that may or may not be related to the study treatment. These medical problems are also known as "adverse events" (AE). The following information regarding safety of darolutamide will be collected during the study:
- the number and severity of AEs that are non-serious or serious
- the number of participants who have to permanently stop the treatment due to AEs
- the number of participants who have to change the amount of study drug taken due to AEs
AEs can be:
- abnormal results of laboratory tests, physical examinations, or heart health examinations using ECG (detects heart problems by measuring the electrical activity generated by the heart as it contracts).
- relevant changes in vital signs
- relevant changes of the participant's daily living abilities (ECOG performance status)
These results will then be compared with the results from the previous study to identify any differences for this group of participants.
In addition, researchers will collect and compare data on how well darolutamide worked under real world conditions in this group of participants.
All participants will take darolutamide as tablets by mouth twice a day. The participants will visit the study center at the start of the study, and then every 16 weeks until their cancer gets worse, they develop medical problems, they leave the study or until the study is terminated.
During the study, the study team will
- take blood and urine samples
- do physical examinations
- check vital signs
- examine heart health using ECG
- assess the participant's ECOG performance status
- ask the participants questions about how they are feeling and what AEs they are having.
If the trial is stopped, participants may have the option to continue to receive darolutamide, provided they benefit from the treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Capable of giving signed informed consent.
- •Participant must be male aged ≥ 18 years.
- •Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features.
- •Castration resistance, demonstrated by:
- •a minimum of 3 rising PSA values while the participant is on continuous ADT (started at least 4 weeks prior to the PSA measurement or, PSA measured at least 4 weeks after bilateral orchiectomy) and
- •the interval between each PSA measurement must be ≥ 1 week, and
- •the PSA value at screening must be ≥ 1.0 ng/mL (1.0 μg/L). To confirm this eligibility criterion, it is acceptable for 2 out of the 3 PSA measurements to be taken during the 28-day screening period (after participant has signed consent), provided the measurements are ≥ 1 week apart. In this case, the last PSA value should be recorded as the screening value.
- •Castrate level of serum testosterone (\< 1.7 nmol/L \[50 ng/dL\]) on gonadotropin releasing hormone (GnRH) agonist or antagonist therapy or after bilateral orchiectomy. Participants who have not undergone bilateral orchiectomy must continue GnRH therapy during the study.
- •PSA doubling time (PSADT) of ≤ 10 months.
- •Eastern cooperative oncology group (ECOG) performance status (PS) of 0 or
Exclusion Criteria
- •History of metastatic disease at any time or presence of detectable metastases by investigator assessment within 42 days prior to start of study treatment based on standard medical imaging, i.e., computed tomography/ magnetic resonance imaging (CT/MRI) and bone scan. (Lesions seen on prostate-specific membrane antigen /positron emission tomography (PSMA/PET) scan that are not detected on standard imaging do not exclude participation.) Presence of pelvic lymph nodes \< 1.5 cm in short axis below the aortic bifurcation is allowed.
- •Symptomatic local-regional disease that requires medical intervention including moderate/severe urinary obstruction or hydronephrosis due to prostate cancer.
- •Acute toxicities of prior treatments and procedures not resolved to common terminology criteria for adverse events (CTCAE) v.5.0 grade ≤ 1 or baseline before first dose of study treatment.
- •Severe or uncontrolled concurrent disease, infection, or co-morbidity that, in the opinion of the investigator, would make the participant inappropriate for enrollment.
- •Known hypersensitivity to the study treatment or any of its ingredients.
- •Major surgery within 28 days before first dose of study treatment.
- •Any of the following within 6 months before first dose of study treatment: 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 systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 100 mmHg at screening despite medical management. Participants with hypertension can enroll provided BP is stable and controlled by anti-hypertensive treatment.
- •End-stage renal disease (eGFR \< 15 mL/min/1.73 m\^2).
- •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 participant has been disease-free.
Arms & Interventions
Darolutamide (BAY1841788)
Participants with high-risk nmCRPC will receive darolutamide.
Intervention: Darolutamide (Nubeqa, BAY1841788)
Outcomes
Primary Outcomes
Number of participants with adverse events (AEs) and serious adverse events (SAEs) and their severity.
Time Frame: Approximately 15 months.
Number of participants with discontinuations of study treatment due to AEs
Time Frame: Approximately 15 months
Number of participants with dose modifications of study treatment due to AEs
Time Frame: Approximately 15 months
Number of participants with clinically significant abnormalities in laboratory parameters
Time Frame: Approximately 15 months
Number of participants with clinically significant electrocardiograms abnormalities
Time Frame: Approximately 15 months
Number of participants with clinically significant physical examination abnormalities
Time Frame: Approximately 15 months
Number of participants with clinically significant changes in vital signs
Time Frame: From baseline to approximately 15 months
Number of participants with changes in eastern cooperative oncology group (ECOG) performance status
Time Frame: From baseline to approximately 15 months
Secondary Outcomes
- Time to initiation of first cytotoxic chemotherapy for prostate cancer(At approximately 15 months)
- PSA maximum percent decline from baseline at any time on study treatment(From baseline to approximately 15 months)
- Prostate-specific antigen (PSA) percent change from baseline to 16 weeks(From baseline to 16 weeks)
- Time to initiation of first subsequent systemic antineoplastic therapy(At approximately 15 months)