Back to resultsProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer
Primary Purpose
Metastatic Castration Resistant Prostate Cancer (mCRPC)
Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CPI-1205
Enzalutamide
Abiraterone/Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Castration Resistant Prostate Cancer (mCRPC) focused on measuring Phase 1/2, Oncology, EZH2 Inhibitor
Eligibility Criteria
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
Sites / Locations
- Alaska Urological Institute
- Beverly Hills Cancer Center (BHCC)
- John Wayne Cancer Inst.
- UCLA
- Rocky Mountain Cancer Centers
- University of Colorado Hospital - Anschutz Cancer Pavilion
- University of Florida
- Mount Sinai Comprehensive Cancer Center
- H. Lee Moffitt Cancer Center & Research Institute
- Rush University Medical Center
- University of Illinois Hospital and Health Systems
- Indiana University- Simon Cancer Center
- Tulane University Health Sciences Center
- University of Maryland
- John Hopkins Kimmel Cancer Center
- Maryland Oncology Hematology
- Dana Farber Cancer Institute
- Henry Ford Health System
- GU Research Network
- Comprehensive Cancer Centers of Nevada
- New Mexico Cancer Center
- Eastchester Center for Cancer Care
- Roswell Park Comprehensive Cancer Center
- North Shore Hematology Oncology Associates
- NYU Langone Medical Center Laura and Isaac Permlutter Cancer Center
- Icahn School of Medicine at Mt. Sinai
- University of North Carolina-Chapel Hill
- Levine Cancer Institute
- Duke University Medical Center
- Ohio State University - James Cancer Hospital and Solove Research Institute
- Toledo Clinic Cancer Center
- Williamette Valley Cancer Institute and Research Center
- Compass Oncology - East
- St. Luke's University
- Gettysburg Cancer Center
- Greenville Hospital System, Institute for Translational Oncology Research
- Carolina Urologic Research Center
- Texas Oncology - Central Austin Cancer Center
- Texas Oncology- Fort Worth
- Texas Oncology- Tyler
- Virginia Oncology Associates
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
CPI-1205 Combination with Enzalutamide
CPI-1205 Combination with Abiraterone/Prednisone
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
PSA50
The proportion of patients with a ≥50% reduction in PSA from baseline.
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.
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
Objective response rate
The proportion of patients with a CR or PR per PCWG3.
Time to PSA progression
Radiographic progression free survival
Time to first skeletal-related event (SRE)
Time to first symptomatic skeletal event (SSE)
Time to clinical progression
Time to initiation of new systemic treatment for prostate cancer
To further evaluate the incidence of Treatment-Emergent Adverse Events (safety and tolerability)
Adverse Events
Pharmacokinetic parameters
Area under the concentration versus time curves (AUC)
Full Information
NCT ID
NCT03480646
First Posted
March 7, 2018
Last Updated
July 23, 2021
Sponsor
Constellation Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03480646
Brief Title
ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Unknown status
Study Start Date
November 15, 2017 (Actual)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Constellation Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Castration Resistant Prostate Cancer (mCRPC)
Keywords
Phase 1/2, Oncology, EZH2 Inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
242 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CPI-1205 Combination with Enzalutamide
Arm Type
Experimental
Arm Title
CPI-1205 Combination with Abiraterone/Prednisone
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
CPI-1205
Intervention Description
Administered orally
Intervention Type
Drug
Intervention Name(s)
Enzalutamide
Intervention Description
Administered orally
Intervention Type
Drug
Intervention Name(s)
Abiraterone/Prednisone
Intervention Description
Administered orally
Primary Outcome Measure Information:
Title
Frequency of Dose-limiting toxicities (DLTs)
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
PSA50
Description
The proportion of patients with a ≥50% reduction in PSA from baseline.
Time Frame
1 year
Title
CTC
Description
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.
Time Frame
1 year
Title
CTC 30% Response Rate
Description
CTC 30% response is defined as a ≥30% reduction in CTCs from baseline in patients who enter the trial with unfavorable CTCs
Time Frame
1 year
Title
Objective response rate
Description
The proportion of patients with a CR or PR per PCWG3.
Time Frame
1 year
Title
Time to PSA progression
Time Frame
1 year
Title
Radiographic progression free survival
Time Frame
1 year
Title
Time to first skeletal-related event (SRE)
Time Frame
1 year
Title
Time to first symptomatic skeletal event (SSE)
Time Frame
1 year
Title
Time to clinical progression
Time Frame
1 year
Title
Time to initiation of new systemic treatment for prostate cancer
Time Frame
1 year
Title
To further evaluate the incidence of Treatment-Emergent Adverse Events (safety and tolerability)
Description
Adverse Events
Time Frame
1 year
Title
Pharmacokinetic parameters
Description
Area under the concentration versus time curves (AUC)
Time Frame
1 year
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Debbie Johnson
Organizational Affiliation
Constellation Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Alaska Urological Institute
City
Anchorage
State/Province
Alaska
ZIP/Postal Code
99503
Country
United States
Facility Name
Beverly Hills Cancer Center (BHCC)
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
John Wayne Cancer Inst.
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Colorado Hospital - Anschutz Cancer Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Mount Sinai Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Illinois Hospital and Health Systems
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Indiana University- Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Tulane University Health Sciences Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
John Hopkins Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Maryland Oncology Hematology
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
GU Research Network
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68130
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89135
Country
United States
Facility Name
New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Eastchester Center for Cancer Care
City
Bronx
State/Province
New York
ZIP/Postal Code
10469
Country
United States
Facility Name
Roswell Park Comprehensive Cancer Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
North Shore Hematology Oncology Associates
City
East Setauket
State/Province
New York
ZIP/Postal Code
11733
Country
United States
Facility Name
NYU Langone Medical Center Laura and Isaac Permlutter Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Icahn School of Medicine at Mt. Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of North Carolina-Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
22710
Country
United States
Facility Name
Ohio State University - James Cancer Hospital and Solove Research Institute
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Toledo Clinic Cancer Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43623
Country
United States
Facility Name
Williamette Valley Cancer Institute and Research Center
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Compass Oncology - East
City
Tualatin
State/Province
Oregon
ZIP/Postal Code
97062
Country
United States
Facility Name
St. Luke's University
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18015
Country
United States
Facility Name
Gettysburg Cancer Center
City
Gettysburg
State/Province
Pennsylvania
ZIP/Postal Code
17331
Country
United States
Facility Name
Greenville Hospital System, Institute for Translational Oncology Research
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Carolina Urologic Research Center
City
Myrtle Beach
State/Province
South Carolina
ZIP/Postal Code
29572
Country
United States
Facility Name
Texas Oncology - Central Austin Cancer Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
Facility Name
Texas Oncology- Fort Worth
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Texas Oncology- Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Virginia Oncology Associates
City
Hampton
State/Province
Virginia
ZIP/Postal Code
23666
Country
United States
12. IPD Sharing Statement
Learn more about this trial
ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer
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