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

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ClinicalTrials.gov Identifier: NCT03480646
Recruitment Status : Recruiting
First Posted : March 29, 2018
Last Update Posted : April 22, 2019
Sponsor:
Information provided by (Responsible Party):
Constellation Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE March 7, 2018
First Posted Date  ICMJE March 29, 2018
Last Update Posted Date April 22, 2019
Actual Study Start Date  ICMJE November 15, 2017
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 1, 2018)
Frequency of Dose-limiting toxicities (DLTs) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2018)
Frequency of Dose-limiting toxicities (DLTs) [ Time Frame: 1 year ]
The RP2D will be selected based on the overall tolerability of each of the combinations (i.e with either enzalutamide or abiraterone/prednisone), but will not exceed the MTD will be selected based on PK and the overall tolerability of the combination, but will not exceed the MTD.
Change History Complete list of historical versions of study NCT03480646 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 1, 2018)
  • PSA50 [ Time Frame: 1 year ]
    The proportion of patients with a ≥50% reduction in PSA from baseline.
  • CTC [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 1 year ]
    The proportion of patients with a CR or PR per PCWG3.
  • Time to PSA progression [ Time Frame: 1 year ]
  • Radiographic progression free survival [ Time Frame: 1 year ]
  • Time to first skeletal-related event (SRE) [ Time Frame: 1 year ]
  • Time to first symptomatic skeletal event (SSE) [ Time Frame: 1 year ]
  • Time to clinical progression [ Time Frame: 1 year ]
  • Time to initiation of new systemic treatment for prostate cancer [ Time Frame: 1 year ]
  • To further evaluate the incidence of Treatment-Emergent Adverse Events (safety and tolerability) [ Time Frame: 1 year ]
    Adverse Events
  • Pharmacokinetic parameters [ Time Frame: 1 year ]
    Area under the concentration versus time curves (AUC)
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2018)
  • PSA50 [ Time Frame: 1 year ]
    The proportion of patients with a ≥50% reduction in PSA from baseline.
  • Time to PSA progression [ Time Frame: 1 year ]
  • Radiographic progression free survival [ Time Frame: 1 year ]
  • Objective response rate [ Time Frame: 1 year ]
    The proportion of patients with a CR or PR per PCWG3.
  • Time to first skeletal-related event (SRE) [ Time Frame: 1 year ]
  • Time to first symptomatic skeletal event (SSE) [ Time Frame: 1 year ]
  • Time to clinical progression [ Time Frame: 1 year ]
  • Time to initiation of new systemic treatment for prostate cancer [ Time Frame: 1 year ]
  • To further evaluate the incidence of Treatment-Emergent Adverse Events (safety and tolerability) [ Time Frame: 1 year ]
    Adverse Events
  • Pharmacokinetic parameters [ Time Frame: 1 year ]
    Area under the concentration versus time curves (AUC)
  • CTC [ Time Frame: 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Castration Resistant Prostate Cancer (mCRPC)
Intervention  ICMJE
  • Drug: CPI-1205
    Administered orally
  • Drug: Enzalutamide
    Administered orally
  • Drug: Abiraterone/Prednisone
    Administered orally
Study Arms  ICMJE
  • Experimental: CPI-1205 Combination with Enzalutamide
    Interventions:
    • Drug: CPI-1205
    • Drug: Enzalutamide
  • Experimental: CPI-1205 Combination with Abiraterone/Prednisone
    Interventions:
    • Drug: CPI-1205
    • Drug: Abiraterone/Prednisone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 1, 2018)
242
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2018)
54
Estimated Study Completion Date  ICMJE August 2020
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Debbie Johnson 617-714-0555 debbie.johnson@constellationpharma.com
Contact: David Nash david.nash@constellationpharmaceuticals.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03480646
Other Study ID Numbers  ICMJE 1205-201
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Constellation Pharmaceuticals
Study Sponsor  ICMJE Constellation Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Debbie Johnson Constellation Pharmaceuticals
PRS Account Constellation Pharmaceuticals
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP