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
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 Dose (RP2D) Based on Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT)
研究概览
简要总结
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.
详细描述
This is an open-label, single-arm, multicenter Phase 1, 3+3 dose-escalation study evaluating CP-PCA07 administered in combination with enzalutamide in patients with castration-resistant prostate cancer (CRPC). A 12-week dose-limiting toxicity (DLT) evaluation period will be implemented for each cohort. A Safety Review Committee (SRC) will function as the independent body for safety monitoring and dose-escalation decisions.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Recommended Phase 2 Dose (RP2D) Based on Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT)
时间窗: Up to 12 weeks after the first dose of the combination therapy
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)
次要结局
- Change From Baseline in Prostate-Specific Antigen (PSA) Levels(Baseline, Week 1 (Day 8), Week 2 (Day 15), Week 4 (Day 29), Week 8 (Day 57), and Week 12 (Day 85))
- Maximum Observed Plasma Concentration (Cmax and Cmax,ss) of Niclosamide, Metabolite M1, and Enzalutamide(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)
- Area Under the Plasma Concentration-Time Curve (AUCt and AUCtau) of Niclosamide, Metabolite M1, and Enzalutamide(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)
- Time to Maximum Observed Plasma Concentration (Tmax and Tmax,ss) of Niclosamide, Metabolite M1, and Enzalutamide(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)
- Elimination Half-life (t1/2) of Niclosamide, Metabolite M1, and Enzalutamide(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)