ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer

Study Overview
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Brief Summary
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This is a two-arm, open label Phase 1b/2 study with an oral administration of CPI-1205 in combination with either enzalutamide or abiraterone/prednisone in male patients with metastatic Castration Resistant Prostate Cancer. This study is designed to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) based on safety, tolerability, pharmacokinetic, and efficacy profiles of CPI-1205 in combination with either enzalutamide or abiraterone/prednisone. Following determination of MTD and RP2D will proceed to phase 2. Patients in phase 2 will receive CPI-1205 at the RP2D in combination with either enzalutamide or abiraterone/prednisone vs either enzalutamide or abiraterone/prednisone as a control arm.

Official Title
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A Phase 1b/2 Study of CPI-1205, a Small Molecule Inhibitor of EZH2, Combined With Enzalutamide or Abiraterone/Prednisone in Patients With Metastatic Castration Resistant Prostate Cancer

Conditions
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Metastatic Castration Resistant Prostate Cancer (mCRPC)

Intervention / Treatment
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* Drug: CPI-1205
* Drug: Enzalutamide
* Drug: Abiraterone/Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (Age ≥ 18 years) Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Life expectancy of at least 12 weeks Histologically or cytologically confirmed adenocarcinoma of the prostate Progressive disease in the setting of medical or surgical castration (i.e. CRPC) Documented metastatic disease Must have undergone bilateral orchiectomy (surgical castration) or be willing to continue gonadotropin-releasing hormone (GnRH) analog or antagonist (medical castration) Serum testosterone <50 ng/dL Receipt of prior line of second generation androgen inhibitor Demonstrate adequate organ function as defined below: Absolute Neutrophil Count (ANC) ≥ 1,000/μL Platelet Count ≥ 100,000/μL Hemoglobin (Hgb) ≥ 8 g/dL Serum creatinine ≤ 2 × upper limit of normal (ULN) OR Creatinine clearance (CrCl) ≥ 40 mL/min as estimated by the Cockcroft and Gault formula1 in subjects with creatinine > 2 X ULN Bilirubin ≤ 1.5 × ULN unless evidence of Gilbert's disease in which case < 3 x ULN Aspartate aminotransferase (AST) ≤ 2.5 × ULN without liver metastases; must be ≤ 5 × ULN with liver metastases Alanine aminotransferase (ALT) ≤ 2.5 × ULN without liver metastases; must be ≤ 5 × ULN with liver metastases Exclusion Criteria: Known symptomatic brain metastases (NOTE: patients with treated epidural disease are allowed) Treatment with any of the following for prostate cancer within the indicated timeframe prior to day 1 of treatment: First generation: AR antagonists (e.g., bicalutamide, nilutamide, flutamide) within 4 weeks 5 alpha reductase inhibitors, ketoconazole, estrogens (including diethylstilbesterol [DES]), or progesterones within 2 weeks Chemotherapy within 3 weeks Biologic therapy within 4 weeks Investigational therapy within 3 weeks (or within a time interval less than at least 5 half-lives of the investigational agent [if known], whichever is longer). Immunotherapy within 4 weeks Prior radionuclide therapy within 4 weeks

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPI-1205 Combination with Enzalutamide<br> | Drug: CPI-1205<br>* Administered orally<br>Drug: Enzalutamide<br>* Administered orally<br>|
| Experimental: CPI-1205 Combination with Abiraterone/Prednisone<br> | Drug: CPI-1205<br>* Administered orally<br>Drug: Abiraterone/Prednisone<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Dose-limiting toxicities (DLTs) | The RP2D will be selected based on PK and the overall tolerability of each of the combinations (i.e with either enzalutamide or abiraterone/prednisone), but will not exceed the MTD. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA50 | The proportion of patients with a ≥50% reduction in PSA from baseline. | 1 year | 
| CTC | In patients who enter the trial with unfavorable CTCs (five or more cells per 7.5mL of blood), conversion to favorable status is defined as four or fewer cells per 7.5 mL of blood. The CTC conversion rate is the proportion of patients who convert to favorable status. | 1 year | 
| CTC 30% Response Rate | CTC 30% response is defined as a ≥30% reduction in CTCs from baseline in patients who enter the trial with unfavorable CTCs | 1 year | 
| Objective response rate | The proportion of patients with a CR or PR per PCWG3. | 1 year | 
| Time to PSA progression |  | 1 year | 
| Radiographic progression free survival |  | 1 year | 
| Time to first skeletal-related event (SRE) |  | 1 year | 
| Time to first symptomatic skeletal event (SSE) |  | 1 year | 
| Time to clinical progression |  | 1 year | 
| Time to initiation of new systemic treatment for prostate cancer |  | 1 year | 
| To further evaluate the incidence of Treatment-Emergent Adverse Events (safety and tolerability) | Adverse Events | 1 year | 
| Pharmacokinetic parameters | Area under the concentration versus time curves (AUC) | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1/2, Oncology, EZH2 Inhibitor