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

NCT03480646

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 1205-201
  • NCT ID: NCT03480646

Conditions

  • Metastatic Castration Resistant Prostate Cancer (mCRPC)

Interventions

DrugSynonymsArms
CPI-1205CPI-1205 Combination with Enzalutamide
EnzalutamideCPI-1205 Combination with Enzalutamide
Abiraterone/PrednisoneCPI-1205 Combination with 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.

Trial Arms

NameTypeDescriptionInterventions
CPI-1205 Combination with EnzalutamideExperimental
  • CPI-1205
  • Enzalutamide
CPI-1205 Combination with Abiraterone/PrednisoneExperimental
  • CPI-1205
  • Abiraterone/Prednisone

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:PSA50
Time Frame:1 year
Safety Issue:
Description:The proportion of patients with a ≥50% reduction in PSA from baseline.
Measure:CTC
Time Frame:1 year
Safety Issue:
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.
Measure:CTC 30% Response Rate
Time Frame:1 year
Safety Issue:
Description:CTC 30% response is defined as a ≥30% reduction in CTCs from baseline in patients who enter the trial with unfavorable CTCs
Measure:Objective response rate
Time Frame:1 year
Safety Issue:
Description:The proportion of patients with a CR or PR per PCWG3.
Measure:Time to PSA progression
Time Frame:1 year
Safety Issue:
Description:
Measure:Radiographic progression free survival
Time Frame:1 year
Safety Issue:
Description:
Measure:Time to first skeletal-related event (SRE)
Time Frame:1 year
Safety Issue:
Description:
Measure:Time to first symptomatic skeletal event (SSE)
Time Frame:1 year
Safety Issue:
Description:
Measure:Time to clinical progression
Time Frame:1 year
Safety Issue:
Description:
Measure:Time to initiation of new systemic treatment for prostate cancer
Time Frame:1 year
Safety Issue:
Description:
Measure:To further evaluate the incidence of Treatment-Emergent Adverse Events (safety and tolerability)
Time Frame:1 year
Safety Issue:
Description:Adverse Events
Measure:Pharmacokinetic parameters
Time Frame:1 year
Safety Issue:
Description:Area under the concentration versus time curves (AUC)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Constellation Pharmaceuticals

Trial Keywords

  • Phase 1/2
  • Oncology
  • EZH2 Inhibitor

Last Updated

October 10, 2019