Clinical trial NCT06801236: Phase 1 Study of ACE-232 to Treat Patients With Metastatic Castration-Resistant Prostate Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Prostate Cancer (Adenocarcinoma)
mCRPC (Metastatic Castration-resistant Prostate Cancer)
Keywords: ACE-232
castration-resistant prostate cancer
CRPC
Hormone Antagonists
Hormone Substitutes
Antineoplastic Agents
Prostatic Neoplasms
Castration-Resistant
prostate cancer
CYP11A1
Lead sponsor: Acerand Therapeutics Limited
Sponsor class: INDUSTRY
First posted: 2025-01-30
Enrollment: 67
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

Eligibility criteria: Inclusion Criteria:

* Provide written informed consent
* Metastatic Castration-resistant Prostate Cancer with ongoing androgen - deprivation therapy (ADT) or have bilateral orchiectomy
* Difficult to treat or intolerant to standard treatment (post at least 1 line of NHA and taxane-based chemo in mHSPC or mCRPC), suitable for investigational treatment;
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Has a life expectancy of at least 6 months
* Adequate organ function and bone marrow function

Exclusion Criteria:

* Receiving any anti-cancer drugs or other treatment, major surgery, extensive radiation therapy, or local radiation therapy within protocol-defined wash-out period;
* Concomitant use of medications or herbal supplements known to be moderate to strong CYP3A4 inhibitors/inducers, or P-gp inhibitors, known to prolong the QT interval.
* Any previous treatment-related toxicities have not recovered.
* Spinal cord compression or known brain metastases or leptomeningeal carcinomatosis.
* Severe cardiovascular disorders.
* Known gastrointestinal (GI) disorder or GI procedure
* History of gastric and duodenal perforation.
* History of pituitary dysfunction.
* Poorly controlled diabetes mellitus.
* Active or uncontrolled autoimmune disease
* Active infections, or a known history of HIV infection, or a known active hepatitis B or C, or a known active tuberculosis.
* Other malignancies requiring treatment within 3 years prior to the first dose of study drug
* Known allergy or hypersensitivity to any of the excipients of ACE-232.
* Has other medical conditions that at the discretion of the investigator interfere with safety or efficacy evaluation, or treatment compliance.

Primary outcomes:
measure: Number of patients experiencing adverse events (AEs)/serious adverse events (SAEs)
timeFrame: From time of information consent to 30 days post last dose, up to approximately 37 months
measure: Number of patients experiencing dose limiting toxicity (DLT), as defined in the protocol
timeFrame: 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)
measure: Recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD)
timeFrame: Up to approximately 37 months
Secondary outcomes:
measure: Pharmacokinetics characterization by using Area under the plasma concentration versus time curve (AUC)
timeFrame: Up to approximately 37 months
measure: Pharmacokinetics characterization by using Maximum concentration (Cmax)
timeFrame: Up to approximately 37 months
measure: Prostate Specific Antigen (PSA) response
timeFrame: Up to approximately 37 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 37 months
measure: Duration of Response (DoR)
timeFrame: Up to approximately 37 months
measure: Radiographic Progression Free Survival (rPFS)
timeFrame: Up to approximately 37 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 37 months
measure: Blood concentration of steroid hormone
timeFrame: Up to approximately 37 months
Other outcomes:
measure: Gene aberrations
timeFrame: Up to approximately 37 months
Locations:
city: La Jolla
country: United States
facility: University of California San Diego, Moores Cancer Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center, Tampa
state: Florida
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Harvard Medical School-Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: M Health Fairview Clinics and Surgery Center
state: Minnesota
city: Omaha
country: United States
facility: Xcancer (Urology Cancer Center)
state: Nebraska
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
References: