Castration-Resistant Prostate Cancer (CRPC)
Conditions
Keywords
Castration-resistant prostate cancer, CRPC, CP-PCA07, Enzalutamide, Niclosamide, Phase 1, Dose escalation
Brief summary
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.
Detailed description
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.
Interventions
DRUGCP-PCA07
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.
DRUGEnzalutamide 40 mg capsule
Enzalutamide will be administered orally once daily at a fixed dose of 160 mg, with or without food, in combination with CP-PCA07.
Sponsors
Hyundai Bioscience Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label, single-arm, multicenter, 3+3 dose-escalation Phase 1 study.
Eligibility
Sex/Gender
MALE
Age
19 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose (RP2D) Based on Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT) | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Descriptive statistics will be presented for the changes in Prostate-Specific Antigen (PSA) levels from baseline to each evaluated post-baseline time point. |
| 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 | 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. |
| 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 | 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 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 | To measure the time to reach maximum plasma concentration (Tmax) at Day 1 and steady-state maximum plasma concentration (Tmax,ss) at Day 29. |
| 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 | 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. |
Countries
South Korea
Contacts
CONTACTHyundai Bioscience Clinical Trial Inquiries
Outcome results
None listed