A Phase 1 Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ACE-232 in Patients With Metastatic Castration-Resistant Prostate Cancer (CRPC)
Summary
This is an open label, phase I, multi-center study aiming to assess the safety and tolerability in patients with metastatic castration resistant prostate cancer (mCRPC).
Detailed description
The study consists of two parts, Phase 1A dose escalation and Phase 1B dose optimization. Phase 1A aims to assess the safety, tolerability, pharmacokinetic (PK) profile, and changes in pharmacodynamic (PD) markers in patients treated with ACE-232, and to determine the maximum tolerated dose (MTD), if applicable. In Phase 1B, patients with AR gene alterations will be treated at two different dose levels to establish the recommended Phase 2 dose (RP2D).
Arms & interventions
- DrugACE-232 tablets
ACE-232 tablets will be administered orally daily as a continuous regimen together with Dexamethasone and Fludrocortisone. Subjects will continue to receive study treatment until PD as judged by local investigator review, development of unacceptable toxicity, or withdrawal of consent.
Outcome measures
Primary
Number of patients experiencing adverse events (AEs)/serious adverse events (SAEs)
Number of patients with incidence of adverse events and with serious adverse events including changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination, etc.
Time frame: From time of information consent to 30 days post last dose, up to approximately 37 months
Number of patients experiencing dose limiting toxicity (DLT), as defined in the protocol
A DLT is defined as any toxicity events related to ACE-232 that occur from the first dose of study treatment until the planned end date of Cycle 1 (DLT assessment period), meeting the criteria specified in protocol.
Time frame: From the first dose of ACE-232 on Cycle 1 Day 1 up to and including the planned end of Cycle 1 (at the end of 28 days)
Recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD)
RP2D will be finally determined by the SMC and sponsor based on all data from the dose escalation module and backfill module, as well as the exposure-response relationship evaluated (if available). MTD is defined as the maximum dose level at which ≤1 patient have DLTs during the DLT observation period, and it should be determined with 6 evaluable patients.
Time frame: Up to approximately 37 months
Secondary
Pharmacokinetics characterization by using Area under the plasma concentration versus time curve (AUC)
Time frame: Up to approximately 37 months
Pharmacokinetics characterization by using Maximum concentration (Cmax)
Time frame: Up to approximately 37 months
Prostate Specific Antigen (PSA) response
Time frame: Up to approximately 37 months
Objective Response Rate (ORR)
Time frame: Up to approximately 37 months
Duration of Response (DoR)
Time frame: Up to approximately 37 months
Radiographic Progression Free Survival (rPFS)
Time frame: Up to approximately 37 months
Overall Survival (OS)
Time frame: Up to approximately 37 months
Blood concentration of steroid hormone
Time frame: Up to approximately 37 months
Eligibility criteria
Study locations (8)
University of California San Diego, Moores Cancer Center
La Jolla, California, 92093
Moffitt Cancer Center, Tampa
Tampa, Florida, 33612
University of Maryland, Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201
Harvard Medical School-Massachusetts General Hospital
Boston, Massachusetts, 02114
M Health Fairview Clinics and Surgery Center
Minneapolis, Minnesota, 55455
Xcancer (Urology Cancer Center)
Omaha, Nebraska, 68130
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109