Phase 3 study of MK-5684 versus alternative NHA in mCRPC post one NHA

JRCT ID: jRCT2031240030

Registered date:12/04/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Prostate cancer metastatic
• Date of first enrollment: 13/05/2024
• Target sample size: 46
• Countries of recruitment: Australia,Japan,Brazil,Japan,Canada,Japan,Chile,Japan,China,Japan,Colombia,Japan,Costa Rica,Japan,Czech Republic,Japan,Estonia,Japan,France,Japan,Germany,Japan,Greece,Japan,Guatemala,Japan,Hong Kong,Japan,Hungary,Japan,Ireland,Japan,Israel,Japan,Italy,Japan,Kenia,Japan,Latvia,Japan,Lithuania,Japan,Malaysia,Japan,Mexico,Japan,New Zealand,Japan,Peru,Japan,Portugal,Japan,Puerto Rico,Japan,Romania,Japan,Singapore,Japan,Slovakia,Japan
• Study type: Interventional

Intervention(s)

Arm 1:Participants will receive MK-5684 5 mg PO BID with hormone replacement therapy of 1.5 mg dexamethasone PO QD and 0.1 mg fludrocortisone acetate PO QD until documented radiographic disease progression, unacceptable AEs, or any other discontinuation criteria is met.

Arm 2:Participants will receive Enzalutamide 160 mg PO QD or Abiraterone acetate 1000 mg PO QD with hormone replacement therapy of 5 mg Prednisolone PO BID until documented radiographic disease progression, unacceptable AEs, or any other discontinuation criteria is met.

Outcome(s)

Primary Outcome

-Radiographic Progression-Free Survival (rPFS)
-Overall Survival (OS)

Secondary Outcome

-Time to Initiation of First Subsequent Anticancer Therapy (TFST)
-Objective Response (OR) and Duration of Response (DOR)
-Time to Pain Progression (TTPP)
-Time to PSA Progression
-PSA Response Rate
-Time to First Symptomatic Skeletal-Related Event
-Safety and Tolerability

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Male

Include criteria

-Have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology
-Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease shown by computed tomography scan (CT)/magnetic resonance imaging (MRI)
-Has prostate cancer progression while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before Screening
-Has disease that progressed during or after treatment with one next-generation hormonal agent (NHA) for hormone sensitive prostate cancer (HSPC) metastatic hormone sensitive prostate cancer (mHSPC) or non metastatic hormone sensitive prostate cancer (nmHSPC), for at least 8 weeks (at least 14 weeks for participants with bone progression) Note: Participants may have received abiraterone acetate and docetaxel or darolutamide and docetaxel for HSPC. However, participants must have received no more than six cycles of docetaxel and had no radiographic disease progression while receiving docetaxel
-Has an eastern clinical oncology group (ECOG) performance status of 0 or 1 assessed within 7 days before randomization
-Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nM)
-Has had prior treatment with Poly polymerase inhibitors (PARPi) or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment
-Has adequate organ function
-Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed
-Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization
-Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at Screening
-Participants who have adverse event (AEs) due to previous anticancer therapies must have recovered to <=Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement therapy (HRT) or participants who have <=Grade 2 neuropathy are eligible
-Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)

Exclude criteria

-Has presence of gastrointestinal condition
-Is unable to swallow capsules/tablets
-Has history of pituitary dysfunction
-Has poorly controlled diabetes mellitus
-Has active or unstable cardio/cerebro-vascular disease, including thromboembolic events
-Has clinically significant abnormal serum potassium or sodium level
-Has any of the following at Screening Visit: Hypotension: systolic BP <110 mmHg, or Uncontrolled hypertension: systolic BP >=160 mmHg or diastolic BP >=90 mmHg, in 2 out of 3 recordings with optimized antihypertensive therapy
-History or family history of long QTc syndrome
-Has a history of seizure(s) within 6 months prior to signing the IC or has any condition that may predispose to seizure within 12 months prior to the date of enrollment
-Has a history of clinically significant ventricular arrhythmias or Mobitz II second degree or third-degree heart block without a permanent pacemaker in place
-Has received a taxane-based chemotherapy and or NHA for metastatic castration-resistant prostate cancer (mCRPC)
-Has not adequately recovered from major surgery or have ongoing surgical complications
-Has received prior treatment with radium for prostate cancer
-Is currently being treated with Cytochrome P450 (CYP450)-inducing antiepileptic drugs for seizures
-Participants on an unstable dose of thyroid hormone therapy within 6 months before the start of the study intervention
-Receives prior radiotherapy within 2 weeks before the first dose of study intervention, or radiation-related toxicities, requiring corticosteroids
-Receives prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
-Has systemic use of strong Cytochrome P450 3A4 (CYP3A4) inducers and P-glycoprotein (P-gp) inhibitors within 2 weeks before the first dose of study intervention
-Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention
-Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
-Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
-Has known hypersensitivity to the components or excipients in abiraterone acetate, prednisone or prednisolone, or enzalutamide
-Has a "superscan" bone scan defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan such that the presence of additional metastases in the future could not be evaluated
-Has known additional malignancy that is progressing or has required active treatment within the past 3 years
-Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
-Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days prior to the first dose of study intervention
-Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is allowed
-Active infection requiring systemic therapy
-Has concurrent active Hepatitis B virus and Hepatitis C virus infection

Related Information

• Primary Sponsor: Koh Yasuhiro
• Source(s) of Monetary Support: Orion Corporation
• Secondary ID(s): NCT06136650