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

• Status: Active, not recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Constellation Pharmaceuticals
• Treatments: (R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide; Prednisone

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