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)

Prostatic Neoplasms Clinical Trial

Official 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06136650
• Other study ID #: 5684-004
• Secondary ID: MK-5684-004jRCT2
• Status: Recruiting
• Phase: Phase 3
• Start date: December 18, 2023
• Est. completion date: December 2, 2030

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: December 2, 2030
• Est. primary completion date: December 2, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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) 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

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer (mCRPC)
• Prostatic Neoplasms

Intervention

Drug:
• Opevesostat
Administered orally
• Dexamethasone
Administered orally
• Fludrocortisone acetate
Administered orally
• Hydrocortisone
Administered orally or IM as a rescue drug
• Abiraterone acetate
Administered orally
• Prednisone acetate
Administered orally
• Enzalutamide
Administered orally

Locations

Country	Name	City	State
Australia	Macquarie University-MQ Health Clinical Trials Unit ( Site 0214)	Macquarie University	New South Wales
Chile	Bradfordhill-Clinical Area ( Site 0301)	Santiago	Region M. De Santiago
Chile	FALP ( Site 0303)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile-Hemato-Oncology ( Site 0304)	Santiago	Region M. De Santiago
Chile	Clinica Universidad Catolica del Maule-Oncology ( Site 0306)	Talca	Maule
Chile	CIDO SpA-Oncology ( Site 0302)	Temuco	Araucania
Chile	ONCOCENTRO APYS-ACEREY ( Site 0305)	Viña del Mar	Valparaiso
China	First Medical Center of Chinese PLA General Hospital ( Site 1601)	Beijing	Beijing
China	Peking University First Hospital-Urology ( Site 1602)	Beijing	Beijing
China	Zhejiang Provincial People's Hospital-Urology ( Site 1641)	Hangzhou	Zhejiang
China	The First Hospital of Jiaxing-urology ( Site 1605)	Jiaxing	Zhejiang
China	Nanchong Central Hospital-urology ( Site 1647)	Nanchong	Sichuan
China	Ningbo First Hospital-Urology ( Site 1608)	Ningbo	Zhejiang
China	Hubei Cancer Hospital-Urinary surgery ( Site 1631)	Wuhan	Hubei
China	Wuxi People's Hospital ( Site 1612)	Wuxi	Jiangsu
Costa Rica	CIMCA-Hemato-Oncology ( Site 0380)	San José	San Jose
Costa Rica	Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 0379)	Santa Ana	San Jose
Czechia	Fakultni Nemocnice u sv. Anny v Brne-Onkologicko-chirurgicke oddeleni ( Site 0404)	Brno	Jihomoravsky Kraj
Czechia	Masarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 0403)	Brno	Brno-mesto
Czechia	Fakultni nemocnice Olomouc-Onkologicka klinika ( Site 0405)	Olomouc
Czechia	Fakultni nemocnice v Motole-Onkologicka klinika 2. LF UK a FN Motol ( Site 0401)	Praha	Praha 5
France	Sainte Catherine Institut du Cancer Avignon Provence ( Site 0458)	Avignon	Vaucluse
France	Centre Hospitalier Régional Universitaire de Brest - Hôpital Morvan ( Site 0456)	Brest	Finistere
France	Institut de cancérologie Strasbourg Europe (ICANS) ( Site 0451)	Strasbourg	Alsace
Germany	Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0504)	Berlin
Germany	Vivantes Klinikum Am Urban ( Site 0512)	Berlin
Germany	klinikum rechts der isar der technischen universität münchen-Urologische Klinik und Poliklinik ( Sit	Munich	Bayern
Germany	Studienpraxis Urologie ( Site 0529)	Nürtingen	Baden-Wurttemberg
Guatemala	Private Practice- Dr. Rixci Augusto Lenin Ramírez ( Site 0577)	Ciudad de Guatemala
Guatemala	CELAN,S.A ( Site 0579)	Guatemala
Guatemala	INTEGRA Cancer Institute-Oncology ( Site 0578)	Guatemala
Hong Kong	Queen Mary Hospital ( Site 0602)	Hksar
Hungary	Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 0631)	Budapest	Pest
Israel	Emek Medical Center ( Site 0680)	Afula
Israel	Rambam Health Care Campus-Oncology Division ( Site 0676)	Haifa
Israel	Hadassah Medical Center ( Site 0683)	Jerusalem
Israel	Shaare Zedek Medical Center ( Site 0679)	Jerusalem
Israel	Meir Medical Center ( Site 0682)	Kfar Saba
Israel	Rabin Medical Center ( Site 0678)	Petah Tikva
Israel	Sheba Medical Center ( Site 0677)	Ramat Gan
Israel	Sourasky Medical Center ( Site 0681)	Tel Aviv
Italy	IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"-Oncologia Medica ( Site 14	Meldola	Emilia-Romagna
Korea, Republic of	Kyungpook National University Chilgok Hospital-Urology ( Site 1252)	Deagu	Taegu-Kwangyokshi
Korea, Republic of	National Cancer Center-Center for Urologic Cancer ( Site 1254)	Goyang-si	Kyonggi-do
Korea, Republic of	Seoul National University Bundang Hospital-Urology ( Site 1253)	Seongnam	Kyonggi-do
Korea, Republic of	Seoul National University Hospital-Urology ( Site 1251)	Seoul
Portugal	2CA BRAGA ( Site 1151)	Braga
Portugal	Hospital CUF - Tejo ( Site 1157)	Lisboa
Portugal	Centro Hospitalar Universitário Lisboa Norte, E.P.E. - Hospi-Centro De Investigaçao Clínica ( Site 1	Lisbon	Lisboa
Portugal	Centro Hospitalar de Vila Nova de Gaia/Espinho - Unidade I ( Site 1156)	Vila Nova de Gaia	Porto
Puerto Rico	Ad-Vance Medical Research-Research ( Site 1177)	Ponce
Puerto Rico	Advance Urology and Laparoscopic Center ( Site 1178)	Ponce
Puerto Rico	Pan American Center for Oncology Trials - Ciudadela ( Site 1176)	San Juan
Romania	Spitalul Universitar de Urgen?a Elias ( Site 1504)	Bucure?ti	Bucuresti
Romania	Cardiomed SRL Cluj-Napoca ( Site 1503)	Cluj-Napoca	Cluj
Romania	Centrul de Oncologie "Sfântul Nectarie" ( Site 1501)	Craiova	Dolj
Romania	SC Radiotherapy Center Cluj SRL ( Site 1502)	Flore?ti	Cluj
Spain	Hospital Universitario de Burgos-Oncología ( Site 1281)	Burgos
Spain	Hospital Quirón Málaga ( Site 1286)	Málaga	Malaga
Spain	HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 1283)	Pozuelo de Alarcon	Madrid
Sweden	Akademiska sjukhuset-Blod- och tumörsjukdomar ( Site 1301)	Uppsala	Uppsala Lan
Taiwan	China Medical University Hospital-Department of Urology ( Site 1335)	Taichung
Taiwan	Chi Mei Medical Center ( Site 1336)	Tainan City	Tainan
Taiwan	Taipei Veterans General Hospital ( Site 1332)	Taipei
Turkey	Hacettepe Universite Hastaneleri-oncology hospital ( Site 1376)	Ankara
United Kingdom	The Royal Cornwall Hospital ( Site 1430)	Truro	England
United States	MidLantic urology ( Site 0022)	Bala-Cynwyd	Pennsylvania
United States	Baltimore Veterans Affairs Medical Center ( Site 0069)	Baltimore	Maryland
United States	St. Vincent Frontier Cancer Center-Research ( Site 0037)	Billings	Montana
United States	University of Virginia Health System ( Site 0054)	Charlottesville	Virginia
United States	Urology Clinics of North Texas, PLLC ( Site 0077)	Dallas	Texas
United States	Edward-Elmhurst Healthcare, Elmhurst Hospital-Nancy W. Knowles Cancer Center ( Site 0074)	Elmhurst	Illinois
United States	The West Clinic, PLLC dba West Cancer Center ( Site 0063)	Germantown	Tennessee
United States	Cancer and Hematology Centers of Western Michigan ( Site 0005)	Grand Rapids	Michigan
United States	Colorado Clinical Research ( Site 0067)	Lakewood	Colorado
United States	Comprehensive Cancer Centers of Nevada ( Site 0010)	Las Vegas	Nevada
United States	OptumCare Cancer Care-Research Department ( Site 0078)	Las Vegas	Nevada
United States	UCLA Hematology/Oncology - Santa Monica ( Site 0044)	Los Angeles	California
United States	Edward-Elmhurst Healthcare, Edward Hospital-Edward Cancer Center ( Site 0075)	Naperville	Illinois
United States	Oncology Hematology West P.C. dba Nebraska Cancer Specialists ( Site 0026)	Omaha	Nebraska
United States	Emad Ibrahim,MD,INC. ( Site 0012)	Redlands	California
United States	VCU Health Adult Outpatient Pavillion ( Site 0061)	Richmond	Virginia
United States	Blue Ridge Cancer Care ( Site 0004)	Roanoke	Virginia
United States	HealthPartners Cancer Research Center-HealthPartners Frauenshuh Cancer Center ( Site 0072)	Saint Louis Park	Minnesota
United States	HealthPartners Cancer Research Center-HealthPartners Cancer Center at Regions Hospital ( Site 0092)	Saint Paul	Minnesota
United States	Chesapeake Urology ( Site 0009)	Towson	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Orion Corporation, Orion Pharma

Countries where clinical trial is conducted

United States,  Australia,  Chile,  China,  Costa Rica,  Czechia,  France,  Germany,  Guatemala,  Hong Kong,  Hungary,  Israel,  Italy,  Korea, Republic of,  Portugal,  Puerto Rico,  Romania,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiographic Progression-free Survival (rPFS)	rPFS is defined as the time from randomization to the first documented disease progression per PCWG-modified RECIST 1.1 by BICR or death due to any cause, whichever occurs first.	Up to approximately 82 months
Primary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 82 months
Secondary	Time to Initiation of the First Subsequent Anticancer Therapy (TFST)	TFST is defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first.	Up to approximately 82 months
Secondary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.	Up to approximately 82 months
Secondary	Duration of Response (DOR)	For participants who demonstrate confirmed CR or PR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression per PCWG-modified RECIST 1.1 as assessed by BICR or death from any cause, whichever occurs first.	Up to approximately 82 months
Secondary	Time to Pain Progression (TTPP)	TTPP is defined as the time from randomization to pain progression. TTTP is assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and opiate analgesic use (Analgesic Quantification Algorithm [AQA] Score).	Up to approximately 82 months
Secondary	Prostrate-specific Antigen (PSA) Response Rate	The Prostate-specific Antigen (PSA) response rate is the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by =50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed =3 weeks from the original response.	Up to approximately 82 months
Secondary	Time to Prostate-specific Antigen (PSA) Progression	The time to PSA progression is the time from randomization to PSA progression. The PSA progression date is defined as the date of: 1) =25% increase and =2 ng/mL above the nadir, confirmed by a second value =3 weeks later if there was PSA decline from baseline; OR 2) =25% increase and =2 ng/mL increase from baseline.	Up to approximately 82 months
Secondary	Time to first symptomatic skeletal-related event (TSSRE)	TSSRE is the time from randomization to the first symptomatic skeletal-related event defined as: 1. use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms 2. occurrence of new symptomatic pathologic bone fracture (vertebral or non-vertebral) 3. occurrence of spinal cord compression 4. tumor-related orthopedic surgical intervention, whichever occurs first.	Up to approximately 82 months
Secondary	Number of Participants Who Experience an Adverse Event (AE)	An AE is defined as any unfavorable and unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience one or more AE will be reported.	Up to approximately 82 months
Secondary	Number of Participants Who Discontinue Study Treatment Due to an AE	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study treatment due to an AE will be reported.	Up to approximately 82 months
Secondary	Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Total Score	The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in participants being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 (not at all) to 4 (very much). The total score can range from 0 to 108. Higher scores indicate higher HRQoL. The change from baseline in FACT-G total score will be reported.	Baseline, and up to approximately 82 months
Secondary	Time to Deterioration (TTD) in FACT-G Total Score	The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in participants being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 (not at all) to 4 (very much). The total score can range from 0 to 108. Higher scores indicate higher HRQoL. TTD in FACT-G total score will be reported.	Up to approximately 82 months
Secondary	Overall Improvement in FACT-G Total Score	The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in participants being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 (not at all) to 4 (very much). The total score can range from 0 to 108. Higher scores indicate higher HRQoL. The overall improvement in FACT-G total score will be reported.	Up to approximately 82 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary