A single-arm, open-label Phase 4 study ofdarolutamide in addition to standard androgendeprivation therapy for participants in India with highrisknon-metastatic castration-resistant prostate cancer(nmCRPC)
Trial Snapshot
- Phase
- Phase 4
- Status
- Recruiting
- Sponsor
- Bayer Consumer Care AG
- Enrollment
- 50
- Locations
- 17
- Primary Endpoint
- Incidence and severity of AEs and SAEs
Study Overview
Brief Summary
Protocol Title:
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)
Short Title: Darolutamide for nmCRPC India PAC study
Rationale: This study aims to demonstrate the safety of darolutamide when administered with
androgen deprivation therapy (ADT) in participants Indian with high-risk non-metastatic
castration-resistant prostate cancer (nmCRPC).
Primary Objectives in this study is :
To characterize the safety profile of
darolutamide in Indian participants with high-risk
nmCRPC.
Secondary Objective in this study is :
To determine the effect of darolutamide on
indicators of efficacy in Indian participants with
high-risk nmCRPC
Study Design
- Study Type
- Interventional
- Allocation
- Not Applicable
- Masking
- Not Applicable
Eligibility Criteria
- Ages
- 18.00 Year(s) to 99.00 Year(s) (—)
- Sex
- Male
Inclusion Criteria
- •Capable of giving signed IC which includes compliance with the requirements, restrictions listed in the informed consent form (ICF), and in this protocol; and providing signed IC.
- •Participant must be male aged ≥ 18 years.
- •Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features.
- •CRPC defined as 3 rising PSA levels after the nadir taken at least 1 week apart during ADT.
- •If the participant has a history of antiandrogen use, the most recent PSA value must be obtained at least 4 weeks after antiandrogen withdrawal.
- •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.
- •PSADT of ≤ 10 months and PSA ≥ 2 ng/mL at screening.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or
- •Estimated glomerular filtration rate (eGFR) > 15 mL/min/1.73 m2
- •Blood counts at screening: hemoglobin ≥ 9.0 g/dL, absolute neutrophil count ≥ 1500/μL (1.5 × 109/L), platelet count ≥ 100,000/μL (100 ×109/L) (participant must not have received any growth factor or blood transfusion within 7 days of the hematology laboratory obtained at screening).
- •Screening values of serum alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2.5 × upper limit of normal (ULN), total bilirubin ≤ 1.5 × ULN (except participants with a diagnosis of Gilbert’s disease), creatinine ≤ 2.0 × ULN.
- •Sexually active participants, unless surgically sterile, must agree to use a male condom plus partner use of a contraceptive method with a failure rate of <1% per year, and refrain from sperm donation during the study treatment and for 1 week after the last dose of study treatment.
- •Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
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.
- •Presence of pelvic lymph nodes < 1.5 cm in short axis below the aortic bifurcation is allowed.
- •Acute toxicities of prior treatments and procedures not resolved to Common Terminology Criteria for Adverse Events (CTCAE) v.4.03 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 m2).
- •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.
- •Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment.
- •Unstable active viral hepatitis with a need for treatment.
- •Known human immunodeficiency virus (HIV) infection with any of the following (Note: HIV testing is not required unless mandated by local authority): CD4+ T-cell (CD4+) count of less than 350 cells/μL History of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the past 12 months On established antiretroviral therapy for less than 4 weeks Presenting with a viral load of more than 400 copies/mL prior to enrollment On antiretroviral therapy or prophylactic antimicrobials that are expected to cause significant drug-drug interactions or overlapping toxicities with study treatment and cannot be changed to alternative agents.
- •Unwilling or unable to comply with all protocol-required visits and assessments or comply with study requirements.
Outcomes
Primary Outcomes
Incidence and severity of AEs and SAEs
Time Frame: From the start of darolutamide treatment up to 30 | days after the last dose of | darolutamide.
Incidence of discontinuations and dose
Time Frame: From the start of darolutamide treatment up to 30 | days after the last dose of | darolutamide.
modifications of study treatment due to
Time Frame: From the start of darolutamide treatment up to 30 | days after the last dose of | darolutamide.
AEs
Time Frame: From the start of darolutamide treatment up to 30 | days after the last dose of | darolutamide.
Laboratory, physical examination, and
Time Frame: From the start of darolutamide treatment up to 30 | days after the last dose of | darolutamide.
ECG abnormalities reported as AEs
Time Frame: From the start of darolutamide treatment up to 30 | days after the last dose of | darolutamide.
Changes in vital signs
Time Frame: From the start of darolutamide treatment up to 30 | days after the last dose of | darolutamide.
Changes in ECOG performance status
Time Frame: From the start of darolutamide treatment up to 30 | days after the last dose of | darolutamide.
Secondary Outcomes
- PSA percent change from baseline at(16 weeks)