Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06353386




Registration number
NCT06353386
Ethics application status
Date submitted
3/04/2024
Date registered
9/04/2024
Date last updated
27/06/2024

Titles & IDs
Public title
Substudy 01A: Safety and Efficacy of Opevesostat (MK-5684)-Based Treatment Combinations or Opevesostat Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-01A)
Scientific title
MK-5684-01A Substudy: A Phase 1/2 Umbrella Substudy of MK-5684-U01 Master Protocol to Evaluate the Safety and Efficacy of MK-5684-based Treatment Combinations or MK-5684 Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC)
Secondary ID [1] 0 0
MK-5684-01A
Secondary ID [2] 0 0
5684-01A
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms, Castration-Resistant 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 - Olaparib
Treatment: Drugs - Docetaxel
Treatment: Drugs - Cabazitaxel
Treatment: Drugs - Fludrocortisone acetate
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Prednisone

Experimental: Arm A1: Opevesostat - Participants receive 5 mg of opevesostat twice daily (BID) via oral tablet plus dexamethasone 1.5 mg by oral tablets once daily (QD) and 0.1 mg fludrocortisone acetate by oral tablet QD until progression or discontinuation.

Experimental: Arm A2: Olaparib + Opevesostat - Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 300 mg of olaparib BID via oral tablet until progressive disease or discontinuation.

Experimental: Arm A3: Docetaxel + Opevesostat - Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 75 mg/m\^2 of docetaxel once every 3 weeks (Q3W) via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.

Experimental: Arm A4: Cabazitaxel + Opevesostat - Participants receive 5 mg of opevesostat BID via oral tablet plus dexamethasone 1.5 mg by oral tablets QD and 0.1 mg fludrocortisone acetate by oral tablet QD, PLUS 20 mg/m\^2 of cabazitaxel Q3W via IV infusion, plus prednisone per approved product label BID by oral tablets until progressive disease or discontinuation.


Treatment: Drugs: Opevesostat
Oral Tablet

Treatment: Drugs: Olaparib
Oral Tablet

Treatment: Drugs: Docetaxel
IV Infusion

Treatment: Drugs: Cabazitaxel
IV Infusion

Treatment: Drugs: Fludrocortisone acetate
Oral Tablet

Treatment: Drugs: Dexamethasone
Oral Tablet

Treatment: Drugs: Prednisone
Oral Tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants who experience one or more dose-limiting toxicities (DLTs)
Timepoint [1] 0 0
Up to approximately 28 days
Primary outcome [2] 0 0
Number of participants who experience one or more adverse events (AEs)
Timepoint [2] 0 0
Up to approximately 46 months
Primary outcome [3] 0 0
Number of participants who discontinue study intervention due to an AE
Timepoint [3] 0 0
Up to approximately 46 months
Primary outcome [4] 0 0
Prostate-specific antigen (PSA) response rate
Timepoint [4] 0 0
Up to approximately 46 months
Secondary outcome [1] 0 0
Objective response rate (ORR)
Timepoint [1] 0 0
Up to approximately 46 months
Secondary outcome [2] 0 0
Radiographic progression-free survival (rPFS)
Timepoint [2] 0 0
Up to approximately 46 months
Secondary outcome [3] 0 0
Overall survival (OS)
Timepoint [3] 0 0
Up to approximately 46 months
Secondary outcome [4] 0 0
Duration of response (DOR)
Timepoint [4] 0 0
Up to approximately 46 months
Secondary outcome [5] 0 0
Time to first subsequent anticancer therapy (TFST)
Timepoint [5] 0 0
Up to approximately 46 months
Secondary outcome [6] 0 0
Time to pain progression (TTPP)
Timepoint [6] 0 0
Up to approximately 46 months

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

* Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate without small cell histology.
* Prostate cancer progression and received androgen deprivation therapy (ADT) or post bilateral orchiectomy within 6 months before screening.
* Evidence of disease progression from either, >4 weeks from last flutamide treatment, or >6 weeks from last bicalutamide or nilutamide treatment, if receiving first generation anti-androgen therapy as last treatment therapy.
* Current evidence of metastatic disease.
* Prior treatment with 1 to 2 novel hormonal agent(s) (NHA) for non-metastatic, or metastatic, hormone-sensitive prostate cancer or castration-resistant prostate cancer and have disease progression during or after treatment.
* Treatment with bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for >4 weeks before randomization.
* Participants who experienced adverse events (AEs) due to previous anticancer therapies must have recovered to <Grade 1 or baseline.
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy.
* 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.
* Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable.
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:

* History of pituitary dysfunction.
* Poorly controlled diabetes mellitus.
* Active or unstable cardio/cerebro-vascular disease, including thromboembolic events.
* History or family history of long corrected QT interval (QTc) syndrome.
* Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or features suggestive of MDS/AML.
* History or current condition of adrenal insufficiency.
* History of (noninfectious) pneumonitis requiring steroids, or current pneumonitis.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Undergone major surgery, including local prostate intervention (except prostate biopsy) within 28 days before randomization, and has not recovered from the toxicities and/or complications.
* Is on an unstable dose of thyroid hormone therapy within 6 months prior to first dose of study intervention.
* Received a whole blood transfusion in the last 120 days before randomization (packed red blood cells and platelet transfusions are acceptable if not given within 28 days before randomization).
* Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
* Received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities, requiring corticosteroids.
* Received a live or live-attenuated vaccine within 30 days before the first does of study intervention. Administration of killed vaccines is allowed.
* Diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy, or any other form of immunosuppressive therapy, within 7 days prior to the first dose of study intervention.
* Known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Active autoimmune disease that has required systemic treatment in the past 2 years.
* Active infection requiring systemic therapy.
* Concurrent active HBV and HCV infections.

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 1
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
20/05/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2028
Actual
Sample size
Target
220
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 0108) - Macquarie University
Recruitment hospital [2] 0 0
Gallipoli Medical Research Ltd-GMRF CTU ( Site 0107) - Greenslopes
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0110) - Melbourne
Recruitment postcode(s) [1] 0 0
2109 - Macquarie University
Recruitment postcode(s) [2] 0 0
4120 - Greenslopes
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Israel
State/province [1] 0 0
Haifa
Country [2] 0 0
Israel
State/province [2] 0 0
Petah Tikva
Country [3] 0 0
Israel
State/province [3] 0 0
Ramat Gan
Country [4] 0 0
Korea, Republic of
State/province [4] 0 0
Seoul
Country [5] 0 0
Taiwan
State/province [5] 0 0
Taichung

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
Substudy 01A is part of a larger research study that is testing experimental treatments for metastatic castration-resistant prostate cancer (mCRPC). The larger study is the umbrella study (U01).

The goal of substudy 01A is to evaluate the safety and efficacy of opevesostat-based treatment combinations, or as a single agent, in participants with mCRPC.

This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for the opevesostat-based treatment combinations. There will be no hypothesis testing in this study.
Trial website
https://clinicaltrials.gov/study/NCT06353386
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/NCT06353386