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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
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.
Enzalutamide will be administered orally once daily at a fixed dose of 160 mg, with or without food, in combination with CP-PCA07.
Seoul National University Hospital
Seoul, South Korea
Recommended Phase 2 Dose (RP2D) Based on Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT)
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)
Time frame: Up to 12 weeks after the first dose of the combination therapy
Change From Baseline in Prostate-Specific Antigen (PSA) Levels
Descriptive statistics will be presented for the changes in Prostate-Specific Antigen (PSA) levels from baseline to each evaluated post-baseline time point.
Time frame: 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
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.
Time frame: 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
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.
Time frame: 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
To measure the time to reach maximum plasma concentration (Tmax) at Day 1 and steady-state maximum plasma concentration (Tmax,ss) at Day 29.
Time frame: 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
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.
Time frame: 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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