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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 : November 5, 2018
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Metastatic Castration Resistant Prostate Cancer (mCRPC) Drug: CPI-1205 Drug: Enzalutamide Drug: Abiraterone/Prednisone Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 242 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 15, 2017
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CPI-1205 Combination with Enzalutamide Drug: CPI-1205
Administered orally

Drug: Enzalutamide
Administered orally

Experimental: CPI-1205 Combination with Abiraterone/Prednisone Drug: CPI-1205
Administered orally

Drug: Abiraterone/Prednisone
Administered orally




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. PSA50 [ Time Frame: 1 year ]
    The proportion of patients with a ≥50% reduction in PSA from baseline.

  2. 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.

  3. 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

  4. Objective response rate [ Time Frame: 1 year ]
    The proportion of patients with a CR or PR per PCWG3.

  5. Time to PSA progression [ Time Frame: 1 year ]
  6. Radiographic progression free survival [ Time Frame: 1 year ]
  7. Time to first skeletal-related event (SRE) [ Time Frame: 1 year ]
  8. Time to first symptomatic skeletal event (SSE) [ Time Frame: 1 year ]
  9. Time to clinical progression [ Time Frame: 1 year ]
  10. Time to initiation of new systemic treatment for prostate cancer [ Time Frame: 1 year ]
  11. To further evaluate the incidence of Treatment-Emergent Adverse Events (safety and tolerability) [ Time Frame: 1 year ]
    Adverse Events

  12. Pharmacokinetic parameters [ Time Frame: 1 year ]
    Area under the concentration versus time curves (AUC)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03480646


Contacts
Contact: Debbie Johnson 617-714-0555 debbie.johnson@constellationpharma.com
Contact: David Nash david.nash@constellationpharmaceuticals.com

  Show 32 Study Locations
Sponsors and Collaborators
Constellation Pharmaceuticals
Investigators
Study Director: Debbie Johnson Constellation Pharmaceuticals

Responsible Party: Constellation Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03480646     History of Changes
Other Study ID Numbers: 1205-201
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: November 5, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Constellation Pharmaceuticals:
Phase 1/2
Oncology
EZH2 Inhibitor

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents