A Phase 1 Clinical Study to Investigate the Safety and Pharmacokinetics of MK-5684 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 3
- 主要终点
- Number of Participants Who Experience an Adverse Event (AE)
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of opevesostat in the treatment of Japanese men with metastatic castration-resistant prostate cancer (mCRPC) previously treated with Next Generation Hormonal Agent (NHA) and taxane-based chemotherapy.
详细描述
After approval of Protocol amendment 03, participants in the survival follow-up phase will have a final survival contact and then be discontinued from the 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 current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI)
- •Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nmol/L)
- •Participants receiving bone anti-resorptive therapy (including, but not limited to bisphosphonate or denosumab) must have been on stable doses for ≥4 weeks prior to the start of study intervention.
- •Has progressed on or after treatment with at least 1 line of NHAs in metastatic hormone-sensitive prostate cancer (mHSPC) or in castration-resistant prostate cancer (CRPC) for a minimum of 12 weeks (e.g. abiraterone, enzalutamide, darolutamide, apalutamide), and with at least 1 line of taxane-based chemotherapy in mHSPC or in CRPC, or ineligibility for chemotherapy
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to allocation
- •If capable of producing sperm, participant must agree to the following during the study treatment period and for at least 7 days after the last dose of opevesostat: Refrain from donating sperm, plus EITHER be abstinent OR must agree to use male condom.
- •Exclusion Criteria:
- •Has a history of pituitary dysfunction
- •Has brain metastases
- •History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
- •Has an active or uncontrolled autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
- •Has an active infection or other medical condition that would make corticosteroid contraindicated
- •Has serious persistent infection within 2 weeks prior to the start of the study intervention
- •Participants on an unstable dose of thyroid hormone therapy within 6 months prior to the start of the study intervention
- •Has poorly controlled diabetes mellitus
- •Hypotension: systolic blood pressure (BP) < 110 mmHg, or uncontrolled hypertension: systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg, in 2 out of 3 recordings with optimized antihypertensive therapy
- •Has active or unstable cardio/cerebro-vascular disease, including thromboembolic event
- •Is unable to swallow orally administered medication or known gastrointestinal (GI) disease or GI procedure that may interfere with absorption of study intervention
- •Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to the start of the study intervention and not adequately recovered from the toxicities and/or complications
- •Has received aldosterone antagonist (e.g. spironolactone, eplerenone) and phenytoin within 4 weeks prior to the start of the study intervention
- •Has received radiotherapy within 4 weeks prior to the start of the study intervention, or radiation related toxicities, requiring corticosteroids
- •Has received chemotherapy within the last 4 weeks (2 weeks for oral or weekly chemotherapy; 6 weeks for nitrosoureas and mitomycin C) prior to the start of the study intervention
- •Has received prior enzalutamide and apalutamide within 3 weeks, or abiraterone and darolutamide within 2 weeks prior to the start of the study intervention
- •Systemic use of the following medications within 2 weeks prior to the start of study intervention: strong cytochrome P450 (CYP)3A4 inducers: e.g., carbamazepine, rifampicin, phenobarbital, phenytoin, St John's Wort) and strong CYP3A4 inhibitors: e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, grapefruit juice
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
- •Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (eg, saw palmetto) within 4 weeks prior to the start of the study intervention
- •Has received treatment with 5-α reductase inhibitors (eg, finasteride or dutasteride), estrogens, and/or cyproterone within 4 weeks prior to the start of the study intervention
- •Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
- •History of human immunodeficiency virus (HIV) infection
- •Has a history of Hepatitis B or active Hepatitis C virus
- •Has a "superscan" bone scan
- •Has a 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 to the start of the study intervention
研究组 & 干预措施
Opevesostat
Participants receive opevesostat 5 mg by oral tablets twice daily plus dexamethasone 1.5 mg by oral tablets and fludrocortisone acetate 0.1 mg oral tablet once daily continuously until progression. Hydrocortisone up to 100 mg oral dose will also be provided to participants for use as rescue medication.
干预措施: Opevesostat (Drug)
Opevesostat
Participants receive opevesostat 5 mg by oral tablets twice daily plus dexamethasone 1.5 mg by oral tablets and fludrocortisone acetate 0.1 mg oral tablet once daily continuously until progression. Hydrocortisone up to 100 mg oral dose will also be provided to participants for use as rescue medication.
干预措施: Dexamethasone (Drug)
Opevesostat
Participants receive opevesostat 5 mg by oral tablets twice daily plus dexamethasone 1.5 mg by oral tablets and fludrocortisone acetate 0.1 mg oral tablet once daily continuously until progression. Hydrocortisone up to 100 mg oral dose will also be provided to participants for use as rescue medication.
干预措施: Fludrocortisone acetate (Drug)
Opevesostat
Participants receive opevesostat 5 mg by oral tablets twice daily plus dexamethasone 1.5 mg by oral tablets and fludrocortisone acetate 0.1 mg oral tablet once daily continuously until progression. Hydrocortisone up to 100 mg oral dose 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 24 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 Experience a Dose-limiting Toxicity (DLT) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 by the Investigator
时间窗: Up to 28 days
The following events, if considered drug related by the Investigator, will be considered a DLT: Grade 4 hematologic toxicity lasting ≥7 days, except anemia and thrombocytopenia; Grade 3 nausea, vomiting, diarrhea or fatigue lasting \>3 days despite optimal supportive care; other nonhematologic grade ≥3 toxicities of any duration (not laboratory); Grade ≥3 nonhematologic laboratory abnormality (if certain criteria are met); febrile neutropenia Grade 3 or Grade 4; missing \>25% of opevesostat doses as a result of drug-related AE(s) during the first 28 days; Grade 5 toxicity. The number of participants who experience a DLT will be presented.
Number of Participants Who Discontinue Study Intervention Due to an AE
时间窗: Up to approximately 24 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.
次要结局
- Time to Maximum Plasma Concentration (Tmax) of opevesostat(Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months))
- Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator(Up to approximately 24 months)
- Maximum Plasma Concentration (Cmax) of opevesostat(Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months))
- Area Under the Curve from Time 0 to 12 hours postdose (AUC0-12) of opevesostat(Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months))
- Half-Life (t½) of opevesostat(Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months))
- Prostate-specific Antigen (PSA) response(Up to approximately 24 months)
- Time to Prostate-specific Antigen (PSA) Progression(Up to approximately 24 months)
- Objective Response Rate (ORR) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator(Up to approximately 24 months)
- Blood Concentrations of Steroids(Day 1, Day 8, Day 29, Day 85, and at first visit after the last dose of opevesostat (up to approximately 24 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) as Assessed by Investigator(Up to approximately 24 months)
- Overall Survival (OS)(Up to approximately 24 months)
- Apparent Volume of Distribution (Vz/F) of opevesostat(Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months))
- Oral Clearance (CL/F) of opevesostat(Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months))