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)
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| ClinicalTrials.gov Identifier: NCT06136650 |
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Recruitment Status :
Recruiting
First Posted : November 18, 2023
Last Update Posted : April 26, 2024
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Sponsor:
Merck Sharp & Dohme LLC
Collaborator:
Orion Corporation, Orion Pharma
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Castration-resistant Prostate Cancer (mCRPC) Prostatic Neoplasms | Drug: Opevesostat Drug: Dexamethasone Drug: Fludrocortisone acetate Drug: Hydrocortisone Drug: Abiraterone acetate Drug: Prednisone acetate Drug: Enzalutamide | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 1500 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | December 18, 2023 |
| Estimated Primary Completion Date : | December 2, 2030 |
| Estimated Study Completion Date : | December 2, 2030 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Prostate cancer
MedlinePlus related topics:
Prostate Cancer
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Opevesostat
Administered orally
Other Name: MK-5684 Drug: Dexamethasone Administered orally Drug: Fludrocortisone acetate Administered orally Drug: Hydrocortisone Administered orally or IM as a rescue drug |
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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.
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Drug: Abiraterone acetate
Administered orally
Other Names:
Drug: Prednisone acetate Administered orally Drug: Enzalutamide Administered orally
Other Name: Xtandi |
Primary Outcome Measures :
- Radiographic Progression-free Survival (rPFS) [ Time Frame: Up to approximately 82 months ]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.
- Overall Survival (OS) [ Time Frame: Up to approximately 82 months ]OS is defined as the time from randomization to death due to any cause.
Secondary Outcome Measures :
- Time to Initiation of the First Subsequent Anticancer Therapy (TFST) [ Time Frame: Up to approximately 82 months ]TFST is defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first.
- Objective Response Rate (ORR) [ Time Frame: Up to approximately 82 months ]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.
- Duration of Response (DOR) [ Time Frame: Up to approximately 82 months ]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.
- Time to Pain Progression (TTPP) [ Time Frame: Up to approximately 82 months ]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).
- Prostrate-specific Antigen (PSA) Response Rate [ Time Frame: Up to approximately 82 months ]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.
- Time to Prostate-specific Antigen (PSA) Progression [ Time Frame: Up to approximately 82 months ]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.
- Time to first symptomatic skeletal-related event (TSSRE) [ Time Frame: Up to approximately 82 months ]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.
- Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 82 months ]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.
- Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 82 months ]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.
- Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Total Score [ Time Frame: Baseline, and up to approximately 82 months ]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.
- Time to Deterioration (TTD) in FACT-G Total Score [ Time Frame: Up to approximately 82 months ]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.
- Overall Improvement in FACT-G Total Score [ Time Frame: Up to approximately 82 months ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06136650
Contacts
| Contact: Toll Free Number | 1-888-577-8839 | Trialsites@merck.com |
Locations
Show 51 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Orion Corporation, Orion Pharma
Investigators
| Study Director: | Medical Director | Merck Sharp & Dohme LLC |
Additional Information:
| Responsible Party: | Merck Sharp & Dohme LLC |
| ClinicalTrials.gov Identifier: | NCT06136650 |
| Other Study ID Numbers: |
5684-004 MK-5684-004 ( Other Identifier: Merck ) jRCT2031240030 ( Registry Identifier: Japan Registry of Clinical Trial (jRCT) ) |
| First Posted: | November 18, 2023 Key Record Dates |
| Last Update Posted: | April 26, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
| URL: | http://engagezone.msd.com/ds_documentation.php |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases, Male Genital Diseases Urogenital Diseases Prostatic Diseases Male Urogenital Diseases Dexamethasone Prednisone Hydrocortisone Fludrocortisone Abiraterone Acetate |
Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Steroid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Hormone Antagonists |