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


Condition: Metastatic Castration Resistant Prostate Cancer (mCRPC)

Intervention:

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

Purpose: 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.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03480646

Sponsor: Constellation Pharmaceuticals

Primary Outcome Measures:

  • Measure: Frequency of Dose-limiting toxicities (DLTs)
  • Time Frame: 1 year
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: PSA50
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: CTC
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: CTC 30% Response Rate
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: Objective response rate
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: Time to PSA progression
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: Radiographic progression free survival
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: Time to first skeletal-related event (SRE)
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: Time to first symptomatic skeletal event (SSE)
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: Time to clinical progression
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: Time to initiation of new systemic treatment for prostate cancer
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: To further evaluate the incidence of Treatment-Emergent Adverse Events (safety and tolerability)
  • Time Frame: 1 year
  • Safety Issue:
  • Measure: Pharmacokinetic parameters
  • Time Frame: 1 year
  • Safety Issue:

Estimated Enrollment: 242

Study Start Date: November 15, 2017

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

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

Contact:

  • Debbie Johnson
  • 617-714-0555

Locations:

  • Alaska Urological Institute
  • Anchorage Alaska 99503 United States
  • Beverly Hills Cancer Center (BHCC)
  • Beverly Hills California 90211 United States
  • John Wayne Cancer Inst.
  • Duarte California 91010 United States
  • UCLA
  • Los Angeles California 90095 United States
  • Rocky Mountain Cancer Centers
  • Aurora Colorado 80045 United States
  • University of Colorado Hospital – Anschutz Cancer Pavilion
  • Aurora Colorado 80045 United States
  • University of Florida
  • Jacksonville Florida 32209 United States
  • Mount Sinai Comprehensive Cancer Center
  • Miami Florida 33140 United States
  • H. Lee Moffitt Cancer Center & Research Institute
  • Tampa Florida 33612 United States
  • Rush University Medical Center
  • Chicago Illinois 60612 United States
  • University of Illinois Hospital and Health Systems
  • Chicago Illinois 60612 United States
  • Indiana University- Simon Cancer Center
  • Indianapolis Indiana 46202 United States
  • Tulane University Health Sciences Center
  • New Orleans Louisiana 70112 United States
  • University of Maryland
  • Baltimore Maryland 21201 United States
  • John Hopkins Kimmel Cancer Center
  • Baltimore Maryland 21205 United States
  • Maryland Oncology Hematology
  • Rockville Maryland 20850 United States
  • Dana Farber Cancer Institute
  • Boston Massachusetts 02115 United States
  • Henry Ford Health System
  • Detroit Michigan 48202 United States
  • GU Research Network
  • Omaha Nebraska 68130 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89135 United States
  • New Mexico Cancer Center
  • Albuquerque New Mexico 87106 United States
  • Eastchester Center for Cancer Care
  • Bronx New York 10469 United States
  • Roswell Park Comprehensive Cancer Center
  • Buffalo New York 14263 United States
  • North Shore Hematology Oncology Associates
  • East Setauket New York 11733 United States
  • NYU Langone Medical Center Laura and Isaac Permlutter Cancer Center
  • New York New York 10016 United States
  • Icahn School of Medicine at Mt. Sinai
  • New York New York 10029 United States
  • University of North Carolina-Chapel Hill
  • Chapel Hill North Carolina 27599 United States
  • Levine Cancer Institute
  • Charlotte North Carolina 28204 United States
  • Duke University Medical Center
  • Durham North Carolina 22710 United States
  • Ohio State University – James Cancer Hospital and Solove Research Institute
  • Columbus Ohio 43210 United States
  • Toledo Clinic Cancer Center
  • Toledo Ohio 43623 United States
  • Williamette Valley Cancer Institute and Research Center
  • Eugene Oregon 97401 United States
  • Compass Oncology – East
  • Tualatin Oregon 97062 United States
  • St. Luke’s University
  • Bethlehem Pennsylvania 18015 United States
  • Gettysburg Cancer Center
  • Gettysburg Pennsylvania 17331 United States
  • Greenville Hospital System, Institute for Translational Oncology Research
  • Greenville South Carolina 29605 United States
  • Carolina Urologic Research Center
  • Myrtle Beach South Carolina 29572 United States
  • Texas Oncology – Central Austin Cancer Center
  • Austin Texas 78731 United States
  • Texas Oncology- Fort Worth
  • Fort Worth Texas 76104 United States
  • Texas Oncology- Tyler
  • Tyler Texas 75702 United States
  • Virginia Oncology Associates
  • Hampton Virginia 23666 United States

View trial on ClinicalTrials.gov


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