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

Phase 1

• Conditions: Metastatic Castration Resistant Prostate Cancer (mCRPC)
• Interventions: Drug: CPI-1205; Drug: Enzalutamide; Drug: Abiraterone/Prednisone

• Registration Number: NCT03480646
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-11-15
• Study First Submitted: 2018-03-07
• Study First Submitted QC: 2018-03-27
• Study First Posted: 2018-03-29
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-23
• Last Update Posted: 2021-07-26
• Primary Completion: 2021-12
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 242

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CPI-1205 Combination with Enzalutamide	CPI-1205	-
CPI-1205 Combination with Enzalutamide	Enzalutamide	-
CPI-1205 Combination with Abiraterone/Prednisone	CPI-1205	-
CPI-1205 Combination with Abiraterone/Prednisone	Abiraterone/Prednisone	-

Primary Outcome Measures

Name	Time	Method
Frequency of Dose-limiting toxicities (DLTs)	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

Name	Time	Method
PSA50	1 year	The proportion of patients with a ≥50% reduction in PSA from baseline.
CTC	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	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	1 year	The proportion of patients with a CR or PR per PCWG3.
Time to PSA progression	1 year
Radiographic progression free survival	1 year
Time to first skeletal-related event (SRE)	1 year
Time to first symptomatic skeletal event (SSE)	1 year
Time to clinical progression	1 year
Time to initiation of new systemic treatment for prostate cancer	1 year
To further evaluate the incidence of Treatment-Emergent Adverse Events (safety and tolerability)	1 year	Adverse Events
Pharmacokinetic parameters	1 year	Area under the concentration versus time curves (AUC)

Trial Locations

Locations (41)

Alaska Urological Institute; 🇺🇸 Anchorage, Alaska, United States

Beverly Hills Cancer Center (BHCC); 🇺🇸 Beverly Hills, California, United States

John Wayne Cancer Inst.; 🇺🇸 Duarte, California, United States

UCLA; 🇺🇸 Los Angeles, California, United States

Rocky Mountain Cancer Centers; 🇺🇸 Aurora, Colorado, United States

University of Colorado Hospital - Anschutz Cancer Pavilion; 🇺🇸 Aurora, Colorado, United States

University of Florida; 🇺🇸 Jacksonville, Florida, United States

Mount Sinai Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

H. Lee Moffitt Cancer Center & Research Institute; 🇺🇸 Tampa, Florida, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

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