A Study of AC176 for the Treatment of Metastatic Castration Resistant Prostate Cancer

NCT05241613 | Terminated Phase 1 FDA Drug

• 1 other identifier: AC176-001
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 5

Brief Summary

This clinical trial is evaluating a drug called AC176 in participants with metastatic castration resistant prostate cancer (mCRPC) who have progressed on at least two prior systemic therapies. The main goals of this study are to:

• Identify the recommended dose of AC176 that can be given safely to participants
• Evaluate the side effects of AC176
• Evaluate pharmacokinetics of AC176
• Evaluate the effectiveness of AC176

Conditions

Metastatic Castration Resistant Prostate Cancer

Keywords

mCRPC; Androgen Receptor; AC176; Phase I; Androgen Receptor Degrader; First in Human

Outcome Measures

Primary Outcomes (5)

• Incidence of dose limiting toxicities (DLTs) from AC176 monotherapy

  Number of subjects with DLT

  28 days

• Adverse events (AEs)/Serious adverse events (SAEs)

  Number of adverse events as characterized by type, frequency, seriousness, and relationship to AC176

  Through study completion, approximately 24 months

• Number of patients with vital signs abnormalities

  Vital signs abnormalities as characterized by type, frequency, severity and timing

  Through study completion, approximately 24 months

• Incidence of laboratory abnormalities as a measure of safety and tolerability of AC176

  Laboratory abnormalities as characterized by type, frequency, severity and timing

  Through study completion, approximately 24 months

• Incidence of Electrocardiogram (ECG) abnormalities as a measure of safety and tolerability of AC176

  Electrocardiogram (ECG) abnormalities such as heart rate, QTcF, PR, RR and QRS intervals

  Through study completion, approximately 24 months

Secondary Outcomes (9)

• Prostate-Specific Antigen (PSA) response rate

  Throughout the study, approximately 24 months

• Title: Duration of Response (DoR)

  Throughout the study, approximately 24 months

• Objective Response Rate(ORR)

  Throughout the study, approximately 24 months

• Time-to-Progression (TTP)

  Throughout the study, approximately 24 months

• Pharmacokinetic Analysis: area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC(0-inf))

  20 weeks

Study Arms (1)

AC176 Dose Escalation as Single Agent

EXPERIMENTAL

Single agent dose escalation of AC176. AC176 will be given orally (PO) on a 28-day cycle.

Drug: AC176

Interventions

AC176 DRUG

AC176 will be given orally (PO) on a 28-day cycle.

AC176 Dose Escalation as Single Agent

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males who are at least 18 years-of-age at the time of signature of the informed consent form (ICF)
• Patients with histological, pathological, or cytological confirmed diagnosis of advanced or mCRPC who have had disease progression per Prostate Cancer Working Group 3(PCWG3) guidance following standard treatment, including approved taxane-based chemotherapy, or who are not amenable (intolerability, patient choice) to standard therapies, or for whom no therapy of proven efficacy exists.
• Advanced or metastatic disease per PCWG3 guidance documented by either:
• Positive bone scan (2 lesions) or metastatic lesions on computed tomography (CT)/magnetic resonance imaging (MRI) that can be followed for response.
• Prostate-specific antigen (PSA) values with a starting value of ≥1.0 ng/mL that have increased on 3 occasions obtained a minimum of 1 week apart.
• Patients must have progressed on at least 2 prior approved systemic therapies (in any setting), with at least 1 being abiraterone, or enzalutamide, or apalutamide or darolutamide
• Patients who have had surgical or medical castration.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 1
• Life expectancy ≥3 months after the start of the treatment according to the Investigator's judgment

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Treatment with any of the following:
• More than 2 lines of chemotherapy
• Any systemic anti-cancer therapy, chemotherapy, biologic, or hormonal agent from a previous treatment regimen or clinical study within 4 weeks prior to the first dose of study drug. Any systemic small molecules from a previous treatment regimen or clinical study within 2 weeks or 5 half-lives (whichever is longer, not to exceed 4 weeks) prior to the first dose of study drug, except ADT for medical castration purpose.
• Any investigational agents from a previous clinical study within 4 weeks prior to the first dose of study treatment
• Radiation therapy (including therapeutic radioisotopes) within 4 weeks prior to first dose of study drug. Radiation for palliation within 2 weeks of study drug. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study
• With the exception of alopecia and ≤ Grade 2 peripheral neuropathy, any unresolved toxicities from prior therapy greater than the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 1 at the time of starting study treatment. Note: subjects with chronic Grade 2 toxicities that are asymptomatic or adequately managed with stable medication may be eligible with Sponsor approval
• Major surgery (excluding placement of vascular access) within 4 weeks of first dose of study drug.
• Known symptomatic brain metastases requiring steroids (above physiologic replacement doses)
• Men who plan to father a child while in the study or within 90 days after the last administration of study treatment
• Any condition that impairs a patient's ability to swallow whole pills. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of AC176 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, malabsorption syndrome)
• Any of the following cardiac criteria experienced currently or within the last 6 months:
• Mean resting corrected QT interval (QTc) \>470 msec
• Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting electrocardiograms (ECGs), e.g., complete left bundle branch block, third-degree heart block
• Congestive heart failure (New York Heart Association ≥ Grade 2)

Sponsors & Collaborators

• Accutar Biotechnology Inc: lead

Study Sites (5)

Site 02

Denver, Colorado, 80218, United States

Location

Site 03

Sarasota, Florida, 34232, United States

Location

Site 05

Detroit, Michigan, 48201, United States

Location

Site 01

Nashville, Tennessee, 37203, United States

Location

Site 04

Dallas, Texas, 75230, United States

Location

MeSH Terms

Conditions

Bulbo-Spinal Atrophy, X-Linked

Condition Hierarchy (Ancestors)

Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2022
• First Posted: February 16, 2022
• Study Start: March 16, 2022
• Primary Completion: March 5, 2024
• Study Completion: March 5, 2024
• Last Updated: February 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)