Clinical trial NCT03480646: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Metastatic Castration Resistant Prostate Cancer (mCRPC)
Keywords: Phase 1/2
Oncology
EZH2 Inhibitor
Lead sponsor: Constellation Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-03-29
Enrollment: 242
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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:

  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

Primary outcomes:
measure: Frequency of Dose-limiting toxicities (DLTs)
timeFrame: 1 year
Secondary outcomes:
measure: PSA50
timeFrame: 1 year
measure: CTC
timeFrame: 1 year
measure: CTC 30% Response Rate
timeFrame: 1 year
measure: Objective response rate
timeFrame: 1 year
measure: Time to PSA progression
timeFrame: 1 year
measure: Radiographic progression free survival
timeFrame: 1 year
measure: Time to first skeletal-related event (SRE)
timeFrame: 1 year
measure: Time to first symptomatic skeletal event (SSE)
timeFrame: 1 year
measure: Time to clinical progression
timeFrame: 1 year
measure: Time to initiation of new systemic treatment for prostate cancer
timeFrame: 1 year
measure: To further evaluate the incidence of Treatment-Emergent Adverse Events (safety and tolerability)
timeFrame: 1 year
measure: Pharmacokinetic parameters
timeFrame: 1 year
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Urological Institute
state: Alaska
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center (BHCC)
state: California
city: Duarte
country: United States
facility: John Wayne Cancer Inst.
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion
state: Colorado
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Hospital and Health Systems
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University- Simon Cancer Center
state: Indiana
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: John Hopkins Kimmel Cancer Center
state: Maryland
city: Rockville
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Omaha
country: United States
facility: GU Research Network
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Albuquerque
country: United States
facility: New Mexico Cancer Center
state: New Mexico
city: Bronx
country: United States
facility: Eastchester Center for Cancer Care
state: New York
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: East Setauket
country: United States
facility: North Shore Hematology Oncology Associates
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center Laura and Isaac Permlutter Cancer Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mt. Sinai
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina-Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University - James Cancer Hospital and Solove Research Institute
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center
state: Ohio
city: Eugene
country: United States
facility: Williamette Valley Cancer Institute and Research Center
state: Oregon
city: Tualatin
country: United States
facility: Compass Oncology - East
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's University
state: Pennsylvania
city: Gettysburg
country: United States
facility: Gettysburg Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Hospital System, Institute for Translational Oncology Research
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Austin
country: United States
facility: Texas Oncology - Central Austin Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology- Fort Worth
state: Texas
city: Tyler
country: United States
facility: Texas Oncology- Tyler
state: Texas
city: Hampton
country: United States
facility: Virginia Oncology Associates
state: Virginia
Study officials:
affiliation: Constellation Pharmaceuticals
name: Debbie Johnson
role: STUDY_DIRECTOR
References: