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).
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).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
67
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.
University of California San Diego, Moores Cancer Center
La Jolla, California, United States
RECRUITINGMoffitt Cancer Center, Tampa
Tampa, Florida, United States
RECRUITINGNumber 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
Pharmacokinetics characterization by using Area under the plasma concentration versus time curve (AUC)
To determine the pharmacokinetics (PK) using AUC of ACE-232 after a single dose and at steady state after multiple doses.
Time frame: Up to approximately 37 months
Pharmacokinetics characterization by using Maximum concentration (Cmax)
To determine the pharmacokinetics (PK) using Cmax of ACE-232 after a single dose and at steady state after multiple doses
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University of Maryland, Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, United States
Harvard Medical School-Massachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGM Health Fairview Clinics and Surgery Center
Minneapolis, Minnesota, United States
RECRUITINGXcancer (Urology Cancer Center)
Omaha, Nebraska, United States
RECRUITINGCarolina Urologic Research Center
Myrtle Beach, South Carolina, United States
RECRUITINGFred Hutchinson Cancer Research Center
Seattle, Washington, United States
NOT_YET_RECRUITINGTime frame: Up to approximately 37 months
Prostate Specific Antigen (PSA) response
PSA response is defined as PSA decline of 30% and 50% from baseline at any time point
Time frame: Up to approximately 37 months
Objective Response Rate (ORR)
ORR is defined as a complete response (CR) or partial response (PR), as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) and Prostate Cancer Working Group Criteria 3 (PCWG3 criteria), in patients with measurable disease at baseline.
Time frame: Up to approximately 37 months
Duration of Response (DoR)
DOR is defined, for patients with an objective response, as the time from first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or death due to any cause.
Time frame: Up to approximately 37 months
Radiographic Progression Free Survival (rPFS)
rPFS is defined as the time from the first dose of ACE-232 to the first documented disease progression by either RECIST progression and/or progression on bone scan by PCWG3 or death due to any cause, whichever occurs first.
Time frame: Up to approximately 37 months
Overall Survival (OS)
OS is defined as the time from the first dose of ACE-232 to the date of death due to any cause.
Time frame: Up to approximately 37 months
Blood concentration of steroid hormone
To determine the blood concentration of steroid hormones at various timepoints and change from baseline
Time frame: Up to approximately 37 months