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

• ClinicalTrials.gov Identifier: NCT03480646
• Recruitment Status: Unknown
• First Posted: March 29, 2018
• Last Update Posted: July 26, 2021
• Sponsor: Constellation Pharmaceuticals
• Information provided by (Responsible Party): Constellation Pharmaceuticals

Tracking Information

• First Submitted Date: March 7, 2018
• First Posted Date: March 29, 2018
• Last Update Posted Date: July 26, 2021
• Actual Study Start Date: November 15, 2017
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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.

Current Secondary Outcome Measures (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 (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: 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

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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Castration Resistant Prostate Cancer (mCRPC)

Intervention

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

Study Arms

• 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

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 1, 2018): 242
• Original Estimated Enrollment (submitted: March 27, 2018): 54
• Estimated Study Completion Date: December 2021
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03480646
• Other Study ID Numbers: 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: Not Provided
• Current Responsible Party: Constellation Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Constellation Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Debbie Johnson; Constellation Pharmaceuticals

• PRS Account: Constellation Pharmaceuticals
• Verification Date: July 2021