Prostatic Neoplasms, Metastatic Castration-Resistant Prostate Cancer
Conditions
Brief summary
The primary objectives of this study are to evaluate the safety and tolerability of opevesostat in the treatment of male Chinese participants with metastatic castration-resistant prostate cancer (mCRPC) and to characterize the pharmacokinetic profile of opevesostat. There are no formal hypotheses to be tested in this study.
Interventions
DRUGOpevesostat
Tablets to be taken orally.
DRUGDexamethasone
Tablets to be taken orally
DRUGFludrocortisone
Tablets to be taken orally.
DRUGHydrocortisone
Tablet to be taken orally as a rescue medication.
Sponsors
Merck Sharp & Dohme LLC
Orion Corporation, Orion Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * Has histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology. * Has prostate cancer while receiving androgen deprivation therapy (ADT), or post-bilateral orchiectomy, within 6 months before screening. * Has evidence of progression \>4 weeks since last flutamide treatment or \>6 weeks since last bicalutamide or nilutamide treatment. * Has evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue shown by CT/MRI. * Has disease that progressed during or after treatment with at least 1 line of next-generation hormonal agents (NHAs) for hormone-sensitive prostate cancer (HSPC) or castration-resistant prostate cancer (CRPC) for at least 8 weeks (at least 14 weeks for participants with bone progression). * Has received at least 1 line of taxane-based chemotherapy for HSPC or CRPC and have had progressed disease during or on treatment, or refused or ineligible to receive chemotherapy. * Has a life expectancy of \>3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oral Clearance (CL/F) of opevesostat | Day 1 and Day 8: predose and 0.5, 1, 2, 3, 4, 6, 9, and 12 hours postdose, Day 29, Day 57, and Day 89: pre-dose | Blood samples will be collected at pre-specified timepoints to determine the CL/F of opevesostat. |
| Half-Life (t1/2) of opevesostat | Day 1 and Day 8: predose and 0.5, 1, 2, 3, 4, 6, 9, and 12 hours postdose, Day 29, Day 57, and Day 89: pre-dose | Blood samples will be collected at pre-specified timepoints to determine the t1/2 of opevesostat. |
| Number of Participants Who Experience an Adverse Event (AE) | Up to approximately 20 months | An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. |
| Number of Participants Who Discontinue Study Intervention Due to an AE | Up to approximately 20 months | An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. |
| Maximum Plasma Concentration (Cmax) of opevesostat | Day 1 and Day 8: predose and 0.5, 1, 2, 3, 4, 6, 9, and 12 hours postdose, Day 29, Day 57, and Day 89: pre-dose | Blood samples will be collected at pre-specified timepoints to determine the Cmax of opevesostat. |
| Time to Maximum Plasma Concentration (Tmax) of opevesostat | Day 1 and Day 8: predose and 0.5, 1, 2, 3, 4, 6, 9, and 12 hours postdose, Day 29, Day 57, and Day 89: pre-dose | Blood samples will be collected at pre-specified timepoints to determine the Tmax of opevesostat. |
| Area Under the Curve from Time 0 to 12 hours postdose (AUC0-12) of opevesostat | Day 1 and Day 8: predose and 0.5, 1, 2, 3, 4, 6, 9, and 12 hours postdose, Day 29, Day 57, and Day 89: pre-dose | Blood samples will be collected at pre-specified timepoints to determine the AUC0-12 of opevesostat. |
| Apparent Volume of Distribution (Vz/F) of opevesostat | Day 1 and Day 8: predose and 0.5, 1, 2, 3, 4, 6, 9, and 12 hours postdose, Day 29, Day 57, and Day 89: pre-dose | Blood samples will be collected at pre-specified timepoints to determine the Vz/F of opevesostat. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) Per PCWG-modified RECIST 1.1 | Up to approximately 37 months | For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per PCWG-modified RECIST 1.1, DOR is defined as the time from first documented evidence of confirmed CR or PR until disease progression or death from any cause, whichever occurs first. |
| Blood Concentrations of Steroids | At designated timepoints (up to approximately 37 months) | Blood samples collected at multiple timepoints after the administration of opevesostat will be used to determine the blood concentrations of steroids. |
| Prostate-specific Antigen (PSA) Response Rate | Up to approximately 37 months | The PSA response rate is defined as the percentage of participants in the analysis population with a reduction in PSA level of ≥50% measured twice ≥3 weeks apart. |
| Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | Up to approximately 37 months | rPFS is defined as the time from first dose of study intervention to radiographic progression per PCWG-modified RECIST 1.1 as assessed by the investigator OR death due to any cause, whichever occurs first. |
| Objective Response Rate (ORR) Per PCWG-modified RECIST 1.1 | Up to approximately 37 months | ORR is defined as the percentage of participants who have a best overall response of either confirmed Complete Response (CR: disappearance of all target lesions) or a confirmed Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per PCWG-modified RECIST 1.1 as assessed by the investigator. |
| Overall Survival (OS) | Up to approximately 37 months | OS is defined as time from first dose of study intervention to death due to any cause. |
Countries
China
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed