Safety, Tolerability, and Efficacy of CP-PCA07 in Combination With Enzalutamide in Patients With Castration-Resistant Prostate Cancer
An Open-Label, Dose-Escalation, Multicenter Phase 1 Study to Evaluate the Safety, Tolerability, and Efficacy of CP-PCA07 in Combination With Enzalutamide in Patients With Castration-Resistant Prostate Cancer
The purpose of this clinical study is to evaluate the safety, tolerability, and efficacy of CP-PCA07 in combination with enzalutamide in patients with castration-resistant prostate cancer (CRPC).
This is an open-label, dose-escalation, multicenter Phase 1 study. The primary objective is to assess the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) to determine the recommended Phase 2 dose (RP2D) of the combination therapy.
The secondary objective is to assess changes in Prostate-Specific Antigen (PSA) levels and pharmacokinetic characteristics.
Exploratory objectives include assessment of tumor response, disease control, progression-free survival, and biomarker analyses, including AR-V7 status, according to RECIST version 1.1 and other applicable criteria.
研究概览
详细说明
研究类型
注册 (估计的)
阶段
- 阶段1
联系人和位置
学习联系方式
- 姓名:Hyundai Bioscience Clinical Trial Inquiries
- 电话号码:+82-1544-3194
- 邮箱:clinical@hyundaibio.com
学习地点
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Seoul、韩国、03080
- Seoul National University Hospital
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首席研究员:
- Chang Wook Jeong, MD, PhD
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- 1. Male patients aged ≥19 years at the time of providing written informed consent.
- 2. Patients with histologically or cytologically confirmed castration-resistant prostate cancer without small-cell features, who have experienced treatment failure with monotherapy of Enzalutamide or Abiraterone.
- 3. Patients with a serum testosterone level < 50 ng/dL at screening.
- 4. Patients with an increase in PSA compared to baseline, confirmed by two consecutive measurements within 8 weeks prior to the date of written informed consent (with at least 1 week between measurements and an increase of ≥ 50% compared to baseline).
- 5. Patients with PSA levels ≥ 2 ng/mL both prior to the date of written informed consent and at screening.
- 6. Patients with an ECOG performance status ≤ 2 and an expected survival of at least 6 months.
- 7. Patients whose spouse or partner is a woman of childbearing potential must agree to use one of the protocol-specified highly effective methods of contraception from the time of study participation consent until 3 months after the last administration of the investigational product.
- 8. Patients who voluntarily agree to participate in this study and provide written informed consent.
Exclusion Criteria:
- 1. Patients who have received chemotherapy, chemoradiotherapy, biologic therapy, immunotherapy, or radiotherapy within 4 weeks prior to the first administration of the investigational product (for docetaxel or cabazitaxel therapy, within 9 weeks prior to the screening date).
- 2. Patients diagnosed with immunodeficiency or who are in an immune-suppressed condition.
- 3. Patients with autoimmune diseases.
- 4. Patients with a pacemaker or severe heart failure [Class III or IV heart failure according to the New York Heart Association (NYHA) classification], or patients with uncontrolled arrhythmia (all patients with implanted medical devices other than a pacemaker are excluded).
- 5. Patients with a history of chronic liver disease or evidence of cirrhosis.
- 6. Patients with a history of gastrectomy or other conditions that may affect drug absorption.
- 7. Patients with a history of deep vein thrombosis, pulmonary embolism, acute coronary syndrome, or major cerebrovascular disease within 6 months prior to screening.
- 8. Patients with a history of major surgery requiring general anesthesia or assisted ventilation within 4 weeks prior to screening.
- 9. Patients with active hepatitis B, a history of hepatitis B, or known active hepatitis C virus infection at screening.
- 10. Patients who meet any of the following laboratory criteria at screening:
- ① Absolute neutrophil count (ANC) < 1,500/uL without G-CSF administration within 2 weeks prior to screening
- ② Platelet < 100,000/uL without transfusion within 2 weeks prior to screening
- ③ Hemoglobin < 9.0 g/dL without transfusion within 2 weeks prior to screening
- ④ Serum creatinine > 1.8 mg/dL or eGFR (or GFR) < 40 mL/min/1.73 m2
- ⑤ AST and ALT > 2.5 x ULN
- ⑥ Total bilirubin > 2.0 x ULN
- 11. Patients expected to have hypersensitivity to the active ingredient or components of the investigational product.
- 12. Patients who have received another investigational drug or investigational medical device within 4 weeks prior to the first administration of the investigational product.
- 13. Patients deemed by the investigator to be unsuitable for participation in the study or unable to comply with the study requirements due to other diseases or conditions.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Enzalutamide + CP-PCA07
Patients will receive combination therapy with CP-PCA07 and Enzalutamide.
Enzalutamide will be administered orally once daily at a fixed dose of 160 mg.
CP-PCA07 will be administered orally three times daily, starting at 600 mg/day, with planned dose escalation to 900 mg/day and 1,200 mg/day according to the protocol-specified 3+3 dose-escalation criteria and dose-limiting toxicity evaluation.
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CP-PCA07 will be administered orally three times daily.
The starting dose is 600 mg/day, with planned escalation to 900 mg/day and 1,200 mg/day based on protocol-specified 3+3 dose-escalation criteria and dose-limiting toxicity evaluation.
其他名称:
Enzalutamide will be administered orally once daily at a fixed dose of 160 mg, with or without food, in combination with CP-PCA07.
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Recommended Phase 2 Dose (RP2D) Based on Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT)
大体时间:Up to 12 weeks after the first dose of the combination therapy
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The recommended Phase 2 dose (RP2D) will be determined by assessing the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) using a 3+3 dose-escalation design.
Safety and tolerability data collected during the first 12 weeks of treatment in each dose cohort will be evaluated by the Safety Review Committee (SRC)
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Up to 12 weeks after the first dose of the combination therapy
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Change From Baseline in Prostate-Specific Antigen (PSA) Levels
大体时间:Baseline, Week 1 (Day 8), Week 2 (Day 15), Week 4 (Day 29), Week 8 (Day 57), and Week 12 (Day 85)
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Descriptive statistics will be presented for the changes in Prostate-Specific Antigen (PSA) levels from baseline to each evaluated post-baseline time point.
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Baseline, Week 1 (Day 8), Week 2 (Day 15), Week 4 (Day 29), Week 8 (Day 57), and Week 12 (Day 85)
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Maximum Observed Plasma Concentration (Cmax and Cmax,ss) of Niclosamide, Metabolite M1, and Enzalutamide
大体时间:Day 1 and Week 4 (Day 29): pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose
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To determine the peak plasma concentration (Cmax) at Day 1 and steady-state peak plasma concentration (Cmax,ss) at Day 29 for Niclosamide (administered as CP-PCA07), its metabolite M1, and Enzalutamide.
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Day 1 and Week 4 (Day 29): pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose
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Area Under the Plasma Concentration-Time Curve (AUCt and AUCtau) of Niclosamide, Metabolite M1, and Enzalutamide
大体时间:Day 1 and Week 4 (Day 29): pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose
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To evaluate the area under the plasma concentration-versus-time curve from time zero to the last quantifiable concentration (AUCt) at Day 1 and during a dosing interval at steady state (AUCtau) at Day 29 to assess systemic exposure.
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Day 1 and Week 4 (Day 29): pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose
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Time to Maximum Observed Plasma Concentration (Tmax and Tmax,ss) of Niclosamide, Metabolite M1, and Enzalutamide
大体时间:Day 1 and Week 4 (Day 29): pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose
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To measure the time to reach maximum plasma concentration (Tmax) at Day 1 and steady-state maximum plasma concentration (Tmax,ss) at Day 29.
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Day 1 and Week 4 (Day 29): pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose
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Elimination Half-life (t1/2) of Niclosamide, Metabolite M1, and Enzalutamide
大体时间:Day 1 and Week 4 (Day 29): pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose
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To estimate the terminal elimination half-life (t1/2) of Niclosamide, its metabolite M1, and Enzalutamide, where mathematically feasible based on the plasma concentration-time profile.
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Day 1 and Week 4 (Day 29): pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post-dose
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
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Objective Response Rate (ORR)
大体时间:At 4, 8, and 12 weeks after the first dose of combination therapy
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The objective response rate is defined as the proportion of patients who achieve a Complete Response (CR) or Partial Response (PR) at the evaluated time points, assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
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At 4, 8, and 12 weeks after the first dose of combination therapy
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Disease Control Rate (DCR)
大体时间:At 12 weeks after the first dose of combination therapy
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The Disease Control Rate is defined as the proportion of patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at 12 weeks after administration, assessed according to RECIST 1.1 criteria.
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At 12 weeks after the first dose of combination therapy
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Incidence of New Metastases
大体时间:Before administration (Baseline) and at 12 weeks after the first dose of combination therapy
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Descriptive statistics will be presented for the incidence and evaluation of new tumor metastases using RECIST 1.1 criteria.
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Before administration (Baseline) and at 12 weeks after the first dose of combination therapy
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合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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