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

Metastatic Castration Resistant Prostate Cancer (mCRPC) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03480646
• Other study ID #: 1205-201
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 15, 2017
• Est. completion date: December 2021

Study information

• Verified date: July 2021
• Source: Constellation Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 242
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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:

1. First generation: AR antagonists (e.g., bicalutamide, nilutamide, flutamide) within 4 weeks

2. 5 alpha reductase inhibitors, ketoconazole, estrogens (including diethylstilbesterol [DES]), or progesterones within 2 weeks

3. Chemotherapy within 3 weeks

4. Biologic therapy within 4 weeks

5. 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).

6. Immunotherapy within 4 weeks

7. Prior radionuclide therapy within 4 weeks

Related Conditions & MeSH terms

• Metastatic Castration Resistant Prostate Cancer (mCRPC)
• Prostatic Neoplasms

Intervention

Drug:
• CPI-1205
Administered orally
• Enzalutamide
Administered orally
• Abiraterone/Prednisone
Administered orally

Locations

Country	Name	City	State
United States	New Mexico Cancer Center	Albuquerque	New Mexico
United States	Alaska Urological Institute	Anchorage	Alaska
United States	Rocky Mountain Cancer Centers	Aurora	Colorado
United States	University of Colorado Hospital - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Texas Oncology - Central Austin Cancer Center	Austin	Texas
United States	John Hopkins Kimmel Cancer Center	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	St. Luke's University	Bethlehem	Pennsylvania
United States	Beverly Hills Cancer Center (BHCC)	Beverly Hills	California
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Eastchester Center for Cancer Care	Bronx	New York
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	University of North Carolina-Chapel Hill	Chapel Hill	North Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois Hospital and Health Systems	Chicago	Illinois
United States	Ohio State University - James Cancer Hospital and Solove Research Institute	Columbus	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	John Wayne Cancer Inst.	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	North Shore Hematology Oncology Associates	East Setauket	New York
United States	Williamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Texas Oncology- Fort Worth	Fort Worth	Texas
United States	Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Greenville Hospital System, Institute for Translational Oncology Research	Greenville	South Carolina
United States	Virginia Oncology Associates	Hampton	Virginia
United States	Indiana University- Simon Cancer Center	Indianapolis	Indiana
United States	University of Florida	Jacksonville	Florida
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	UCLA	Los Angeles	California
United States	Mount Sinai Comprehensive Cancer Center	Miami	Florida
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Icahn School of Medicine at Mt. Sinai	New York	New York
United States	NYU Langone Medical Center Laura and Isaac Permlutter Cancer Center	New York	New York
United States	GU Research Network	Omaha	Nebraska
United States	Maryland Oncology Hematology	Rockville	Maryland
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Toledo Clinic Cancer Center	Toledo	Ohio
United States	Compass Oncology - East	Tualatin	Oregon
United States	Texas Oncology- Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Constellation Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	PSA50	The proportion of patients with a =50% reduction in PSA from baseline.	1 year
Secondary	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
Secondary	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
Secondary	Objective response rate	The proportion of patients with a CR or PR per PCWG3.	1 year
Secondary	Time to PSA progression		1 year
Secondary	Radiographic progression free survival		1 year
Secondary	Time to first skeletal-related event (SRE)		1 year
Secondary	Time to first symptomatic skeletal event (SSE)		1 year
Secondary	Time to clinical progression		1 year
Secondary	Time to initiation of new systemic treatment for prostate cancer		1 year
Secondary	To further evaluate the incidence of Treatment-Emergent Adverse Events (safety and tolerability)	Adverse Events	1 year
Secondary	Pharmacokinetic parameters	Area under the concentration versus time curves (AUC)	1 year