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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06136650




Registration number
NCT06136650
Ethics application status
Date submitted
13/11/2023
Date registered
18/11/2023
Date last updated
27/06/2024

Titles & IDs
Public title
A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004)
Scientific title
A Phase 3, Randomized, Open-label Study of MK-5684 Versus Alternative Abiraterone Acetate or Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) That Progressed On or After Prior Treatment With One Next-generation Hormonal Agent (NHA)
Secondary ID [1] 0 0
MK-5684-004
Secondary ID [2] 0 0
5684-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration-resistant Prostate Cancer (mCRPC) 0 0
Prostatic Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Opevesostat
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Fludrocortisone acetate
Treatment: Drugs - Hydrocortisone
Treatment: Drugs - Abiraterone acetate
Treatment: Drugs - Prednisone acetate
Treatment: Drugs - Enzalutamide

Experimental: hormone replacement therapy (HRT)+ opevesostat - Participants receive opevesostat 5 mg by oral tablets twice daily (BID) plus dexamethasone 1.5 mg by oral tablets and fludrocortisone acetate 0.1 mg oral tablet once daily (QD) continuously until disease progression. Hydrocortisone 100 mg (oral or intramuscular \[IM\]) will also be provided to participants for use as rescue medication.

Active comparator: Alternative next generation hormonal agent (NHA) - Participants receive Abiraterone 1000 mg QD by oral tablets plus Prednisone 5 mg BID by oral tablets or Enzalutamide 160 mg QD by oral tablets until disease progression.


Treatment: Drugs: Opevesostat
Administered orally

Treatment: Drugs: Dexamethasone
Administered orally

Treatment: Drugs: Fludrocortisone acetate
Administered orally

Treatment: Drugs: Hydrocortisone
Administered orally or IM as a rescue drug

Treatment: Drugs: Abiraterone acetate
Administered orally

Treatment: Drugs: Prednisone acetate
Administered orally

Treatment: Drugs: Enzalutamide
Administered orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Radiographic Progression-free Survival (rPFS)
Timepoint [1] 0 0
Up to approximately 82 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 82 months
Secondary outcome [1] 0 0
Time to Initiation of the First Subsequent Anticancer Therapy (TFST)
Timepoint [1] 0 0
Up to approximately 82 months
Secondary outcome [2] 0 0
Objective Response Rate (ORR)
Timepoint [2] 0 0
Up to approximately 82 months
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
Up to approximately 82 months
Secondary outcome [4] 0 0
Time to Pain Progression (TTPP)
Timepoint [4] 0 0
Up to approximately 82 months
Secondary outcome [5] 0 0
Prostrate-specific Antigen (PSA) Response Rate
Timepoint [5] 0 0
Up to approximately 82 months
Secondary outcome [6] 0 0
Time to Prostate-specific Antigen (PSA) Progression
Timepoint [6] 0 0
Up to approximately 82 months
Secondary outcome [7] 0 0
Time to first symptomatic skeletal-related event (TSSRE)
Timepoint [7] 0 0
Up to approximately 82 months
Secondary outcome [8] 0 0
Number of Participants Who Experience an Adverse Event (AE)
Timepoint [8] 0 0
Up to approximately 82 months
Secondary outcome [9] 0 0
Number of Participants Who Discontinue Study Treatment Due to an AE
Timepoint [9] 0 0
Up to approximately 82 months
Secondary outcome [10] 0 0
Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Total Score
Timepoint [10] 0 0
Baseline, and up to approximately 82 months
Secondary outcome [11] 0 0
Time to Deterioration (TTD) in FACT-G Total Score
Timepoint [11] 0 0
Up to approximately 82 months
Secondary outcome [12] 0 0
Overall Improvement in FACT-G Total Score
Timepoint [12] 0 0
Up to approximately 82 months

Eligibility
Key inclusion criteria
The main inclusion criteria include but are not limited to the following:

* 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The main exclusion criteria include but are not limited to the following:

* Has presence of gastrointestinal condition
* Is unable to swallow capsules/tablets
* Has history of pituitary dysfunction
* Has poorly controlled diabetes mellitus
* Has a history of 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 blood pressure (BP) <110 mmHg, or Uncontrolled hypertension: systolic BP >160mmHg or diastolic blood BP >90 mmHg, in 2 out of the 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 informed consent (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, enzalutamide, fludrocortisone, dexamethasone, or opevesostat.
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
2/12/2030
Actual
Sample size
Target
1500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Macquarie University-MQ Health Clinical Trials Unit ( Site 0214) - Macquarie University
Recruitment hospital [2] 0 0
Westmead Hospital-Department of Medical Oncology ( Site 0212) - Westmead
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si - Brisbane
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0210) - Melbourne
Recruitment postcode(s) [1] 0 0
2109 - Macquarie University
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Brisbane
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment outside Australia
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Maule
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Chile
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Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Orion Corporation, Orion Pharma
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the efficacy and safety of opevesostat plus hormone replacement therapy (HRT) compared to alternative abiraterone acetate or enzalutamide in participants with Metastatic Castration-resistant Prostate Cancer (mCRPC) previously treated with one next-generation hormonal agent (NHA). The primary study hypotheses are that opevesostat is superior to alternative abiraterone acetate or enzalutamide with respect to radiographic progression free survival (rPFS) per Prostate Cancer Working Group (PCWG) Modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) and overall survival (OS), in androgen receptor ligand binding domain (AR LBD) mutation positive and negative participants.
Trial website
https://clinicaltrials.gov/study/NCT06136650
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06136650