ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer
- Conditions
- Metastatic Castration Resistant Prostate Cancer (mCRPC)
- Interventions
- Registration Number
- NCT03480646
- Lead Sponsor
- Constellation Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Male
- Target Recruitment
- 242
-
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
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Progressive disease in the setting of medical or surgical castration (i.e. CRPC)
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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
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Receipt of prior line of second generation androgen inhibitor
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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
-
Known symptomatic brain metastases (NOTE: patients with treated epidural disease are allowed)
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CPI-1205 Combination with Enzalutamide CPI-1205 - CPI-1205 Combination with Enzalutamide Enzalutamide - CPI-1205 Combination with Abiraterone/Prednisone CPI-1205 - CPI-1205 Combination with Abiraterone/Prednisone Abiraterone/Prednisone -
- Primary Outcome Measures
Name Time Method Frequency of Dose-limiting toxicities (DLTs) 1 year 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
Name Time Method PSA50 1 year The proportion of patients with a ≥50% reduction in PSA from baseline.
CTC 1 year 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 1 year 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 1 year The proportion of patients with a CR or PR per PCWG3.
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) 1 year Adverse Events
Pharmacokinetic parameters 1 year Area under the concentration versus time curves (AUC)
Trial Locations
- Locations (41)
University of Illinois Hospital and Health Systems
🇺🇸Chicago, Illinois, United States
John Hopkins Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Williamette Valley Cancer Institute and Research Center
🇺🇸Eugene, Oregon, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
NYU Langone Medical Center Laura and Isaac Permlutter Cancer Center
🇺🇸New York, New York, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Ohio State University - James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Eastchester Center for Cancer Care
🇺🇸Bronx, New York, United States
Gettysburg Cancer Center
🇺🇸Gettysburg, Pennsylvania, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Alaska Urological Institute
🇺🇸Anchorage, Alaska, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
University of Florida
🇺🇸Jacksonville, Florida, United States
St. Luke's University
🇺🇸Bethlehem, Pennsylvania, United States
Texas Oncology - Central Austin Cancer Center
🇺🇸Austin, Texas, United States
Rocky Mountain Cancer Centers
🇺🇸Aurora, Colorado, United States
Icahn School of Medicine at Mt. Sinai
🇺🇸New York, New York, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Beverly Hills Cancer Center (BHCC)
🇺🇸Beverly Hills, California, United States
John Wayne Cancer Inst.
🇺🇸Duarte, California, United States
UCLA
🇺🇸Los Angeles, California, United States
Indiana University- Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Maryland Oncology Hematology
🇺🇸Rockville, Maryland, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
Compass Oncology - East
🇺🇸Tualatin, Oregon, United States
Greenville Hospital System, Institute for Translational Oncology Research
🇺🇸Greenville, South Carolina, United States
Toledo Clinic Cancer Center
🇺🇸Toledo, Ohio, United States
North Shore Hematology Oncology Associates
🇺🇸East Setauket, New York, United States
Texas Oncology- Fort Worth
🇺🇸Fort Worth, Texas, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
University of North Carolina-Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Virginia Oncology Associates
🇺🇸Hampton, Virginia, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
Texas Oncology- Tyler
🇺🇸Tyler, Texas, United States
GU Research Network
🇺🇸Omaha, Nebraska, United States