A Phase 1 Clinical Study to Investigate the Safety and Pharmacokinetics of MK-5684 in China Participants With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 14
- 试验地点
- 6
- 主要终点
- Number of Participants Who Experience an Adverse Event (AE)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •The main inclusion and
排除标准
- •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.
- •Exclusion Criteria:
- •Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.
- •Has presence of gastrointestinal condition, e.g. malabsorption, that might affect the adsorption of study intervention.
- •Has a history of pituitary dysfunction.
- •Has poorly controlled diabetes mellitus.
- •Has active or unstable cardio/cerebro-vascular disease, including thromboembolic events.
- •Has undergone major surgery, including local prostate intervention (except prostate biopsy), within 4 weeks of the date of allocation.
- •Has received an anticancer monoclonal antibody (mAb) within 4 weeks of allocation, or has not recovered from adverse events (AEs) due to mAbs administered more than 4 weeks before the date of allocation.
- •Received prior systemic anticancer therapy including investigational agents within 4 weeks before the date of allocation.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any form of immunosuppressive therapy within 7 days prior to the start of study intervention.
- •Has a known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years.
- •Has a history of or current human immunodeficiency virus (HIV) infection.
- •Has a concurrent Hepatitis B or Hepatitis C virus infection.
- •Has a history of allogenic tissue or solid organ transplant.
研究组 & 干预措施
Opevesostat
Participants will receive opevesostat by oral tablets twice daily plus dexamethasone and fludrocortisone by oral tablets once daily continuously until unacceptable toxicity or documented progression. Hydrocortisone will also be provided to participants for use as rescue medication.
干预措施: Opevesostat (Drug)
Opevesostat
Participants will receive opevesostat by oral tablets twice daily plus dexamethasone and fludrocortisone by oral tablets once daily continuously until unacceptable toxicity or documented progression. Hydrocortisone will also be provided to participants for use as rescue medication.
干预措施: Dexamethasone (Drug)
Opevesostat
Participants will receive opevesostat by oral tablets twice daily plus dexamethasone and fludrocortisone by oral tablets once daily continuously until unacceptable toxicity or documented progression. Hydrocortisone will also be provided to participants for use as rescue medication.
干预措施: Fludrocortisone (Drug)
Opevesostat
Participants will receive opevesostat by oral tablets twice daily plus dexamethasone and fludrocortisone by oral tablets once daily continuously until unacceptable toxicity or documented progression. Hydrocortisone will also be provided to participants for use as rescue medication.
干预措施: Hydrocortisone (Drug)
结局指标
主要结局
Number of Participants Who Experience an Adverse Event (AE)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
Oral Clearance (CL/F) of opevesostat
时间窗: 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
时间窗: 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.
次要结局
- Prostate-specific Antigen (PSA) Response Rate(Up to approximately 37 months)
- 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)
- Objective Response Rate (ORR) Per PCWG-modified RECIST 1.1(Up to approximately 37 months)
- Duration of Response (DOR) Per PCWG-modified RECIST 1.1(Up to approximately 37 months)
- Overall Survival (OS)(Up to approximately 37 months)
- Blood Concentrations of Steroids(At designated timepoints (up to approximately 37 months))