AC176 for Prostate Cancer

No longer recruiting at 4 trial locations

Overseen By Accutar Biotechnology

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Accutar Biotechnology Inc

Must be taking: Abiraterone, Enzalutamide, Apalutamide, Darolutamide

Must not be taking: Chemotherapy, Biologics, Hormonal agents

Disqualifiers: Brain metastases, Cardiac issues, Gastrointestinal conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug, AC176, for men with advanced prostate cancer that no longer responds to standard treatments. Researchers aim to determine the safest dose, identify side effects, and evaluate AC176's effectiveness. The study seeks men whose prostate cancer has spread and who have tried at least two other treatments without success. Participants will take AC176 orally in cycles to assess its effects. As a Phase 1 trial, participants will be among the first to receive AC176, aiding researchers in understanding how this new treatment works in people.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anti-cancer therapy, chemotherapy, biologic, or hormonal agent from a previous treatment regimen within 4 weeks before starting the study drug, except for medications used for medical castration. If you're on any investigational agents, you must stop them 4 weeks before the study. Please discuss your specific medications with the study team to ensure compliance.

Is there any evidence suggesting that AC176 is likely to be safe for humans?

Research has shown that AC176, also known as apalutamide, is being tested for safety in people with advanced prostate cancer that no longer responds to hormone therapy. Early results suggest that AC176 may cause side effects such as skin reactions and other issues. The current study aims to find a safe dose, so researchers are still learning how people respond to AC176.

Since this trial is in the early stages, it focuses on finding the right dose and monitoring for any side effects. This step is crucial before confirming its safety. The safety data will help determine how well people can tolerate AC176, but more research is needed to fully understand its effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for prostate cancer, which typically includes surgery, radiation, and hormone therapy, AC176 is unique because it is an oral medication designed for dose escalation. Researchers are excited about AC176 as it offers a potentially less invasive treatment option that patients can take by mouth, which may improve patient comfort and adherence. Additionally, its novel approach could target prostate cancer cells differently, possibly leading to new pathways for managing the disease.

What evidence suggests that AC176 might be an effective treatment for prostate cancer?

Research has shown that AC176 targets specific proteins called androgen receptors, which contribute to prostate cancer growth. In studies, patients with advanced prostate cancer who experienced significant drops in their PSA (prostate-specific antigen) levels had better outcomes. A deep PSA response, defined as a 90% reduction in PSA levels, indicates lower cancer activity. Evidence suggests that AC176 may effectively slow cancer progression in patients who have already tried other treatments. This offers hope that AC176 could be a promising option for those battling aggressive prostate cancer. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for males over 18 with advanced prostate cancer that's resistant to castration and has worsened after at least two systemic therapies. Participants must have a life expectancy of more than three months, be able to swallow pills, and not plan on fathering children during the study.

Inclusion Criteria

I have undergone surgical or medical castration.

My cancer has worsened after two treatments, including one like abiraterone.

My advanced cancer is confirmed by scans or rising PSA levels.

Exclusion Criteria

I haven't taken any cancer treatment drugs or participated in a clinical study for at least 4 weeks.

I need steroids for my brain metastases symptoms.

My heart's pumping ability is below normal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AC176 orally on a 28-day cycle in a dose-escalation study

28 days per cycle

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• AC176

Trial Overview The drug AC176 is being tested in this trial. It aims to find a safe dose, understand side effects, how the body processes it (pharmacokinetics), and its effectiveness against metastatic castration-resistant prostate cancer.

How Is the Trial Designed?

Group I: AC176 Dose Escalation as Single Agent Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Accutar Biotechnology Inc

Lead Sponsor

Trials

6

Recruited

180+

Published Research Related to This Trial

In the SPARTAN study, apalutamide combined with androgen deprivation therapy (ADT) led to rapid and significant reductions in prostate-specific antigen (PSA) levels in most patients, with 90% achieving at least a 50% reduction by 6 months, compared to only 1.5% in the placebo group.

Deep PSA responses (≥90% reduction or PSA ≤0.2 ng/ml) at 6 months were strongly linked to improved outcomes, including metastasis-free survival and overall survival, indicating that early PSA monitoring can be a valuable prognostic tool for patients with high-risk nonmetastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN. Saad, F., Small, EJ., Feng, FY., et al.[2022]

In a study of 107 patients with advanced prostate cancer, reducing the dose of apalutamide did not significantly change the overall rate of skin-related adverse events (AEs) compared to full doses.

However, patients with smaller body sizes experienced fewer skin-related AEs when on a reduced dose, and this dose reduction did not negatively impact their cancer-free survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of apalutamide dose reduction on skin-related adverse events in patients with advanced prostate cancer: A multicenter retrospective study. Oishi, T., Hatakeyama, S., Tabata, R., et al.[2023]

In a study of 699 non-metastatic castration-resistant prostate cancer patients treated with apalutamide or enzalutamide, 75.1% experienced at least one adverse event (AE), with fatigue, hot flushes, and joint pain being the most common.

Management of AEs included specific treatments for the symptoms, discontinuation of the androgen receptor inhibitors in 10.4% of cases, and hospitalization in 4.8%, indicating a significant burden of side effects in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world burden of adverse events for apalutamide- or enzalutamide-treated non-metastatic castration-resistant prostate cancer patients in the United States. Hussain, A., Jiang, S., Varghese, D., et al.[2022]

In the SPARTAN study, apalutamide significantly improved overall survival (OS) in patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC), showing a 25% reduction in the risk of death compared to placebo after a median follow-up of 41 months.

Apalutamide also enhanced second progression-free survival (PFS2) by 45%, indicating its efficacy in delaying disease progression, with no new safety concerns reported during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Small, EJ., Saad, F., Chowdhury, S., et al.[2023]

In the SPARTAN study involving 1207 patients with nonmetastatic castration-resistant prostate cancer, apalutamide significantly improved health-related quality of life (HRQoL) compared to placebo, with patients maintaining better scores over time.

Patients receiving apalutamide experienced minimal side effects and reported no worsening of fatigue, while those on placebo showed a decline in quality of life after about one year, highlighting the efficacy and tolerability of apalutamide in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. Oudard, S., Hadaschik, B., Saad, F., et al.[2022]

The ARNEO trial is a phase II study involving at least 84 patients with intermediate to high-risk prostate cancer, aiming to evaluate the effectiveness of combining apalutamide with degarelix compared to degarelix alone in reducing minimal residual disease after surgery.

This study will also explore the molecular effects of the treatment on tumors and assess various clinical outcomes, including PSA levels, testosterone levels, and quality of life, providing comprehensive insights into the safety and efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial. Tosco, L., Laenen, A., Gevaert, T., et al.[2018]

ARAT agents like abiraterone acetate and enzalutamide improve survival rates in advanced prostate cancer but are associated with significant endocrine and metabolic side effects, such as hypertension and insulin resistance.

Darolutamide appears to have a safer side effect profile compared to other ARAT agents, suggesting that treatment for advanced prostate cancer should be personalized based on individual patient safety and risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine consequences of treatment with the new androgen receptor axis-targeted agents for advanced prostate cancer. Pyrgidis, N., Vakalopoulos, I., Sountoulides, P.[2021]

Citations

1. withpower.com withpower.com/trial/phase-1-prostatic-neoplasms-2-2022-2d9ef

AC176 for Prostate Cancer · Info for Participants Deep PSA responses (≥90% reduction or PSA ≤0.2 ng/ml) at 6 months were strongly linked to improved outcomes, including metastasis-free survival and overall ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10854644/

Insight into Recent Advances in Degrading Androgen ... A promising approach to combat aggressive prostate cancer involves androgen receptor degraders, which break down the crucial protein driving cancer progression.

3. cancerbiomed.org cancerbiomed.org/content/22/5/433/tab-figures-data

Advances in the treatment of metastatic prostate cancer ... AC176, NCT05673109, China, mCRPC ... Focal ablation therapy presents promising results for selectively localized prostate cancer patients.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05241613

A Study of AC176 for the Treatment of Metastatic Castration ... This clinical trial is evaluating a drug called AC176 in participants with metastatic castration resistant prostate cancer (mCRPC) who have progressed on at ...

5. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05673109/

Trial | NCT05673109 This clinical trial is evaluating a drug called AC176 in Chinese participants with metastatic castration resistant prostate cancer (mCRPC) who have ...

6. trial.medpath.com trial.medpath.com/clinical-trial/48b04e1c6598cf3d

A Study of AC176 for the Treatment of Metastatic Castration ... This clinical trial is evaluating a drug called AC176 in participants with metastatic castration resistant prostate cancer (mCRPC) who have progressed on at ...

7. clinicaltrials.med.nyu.edu clinicaltrials.med.nyu.edu/cancer/clinicaltrial/2110/phase-i-open-label-multi-center/

Perlmutter Cancer Center - Clinical Trials The study will identify a maximum tolerated dose (MTD) if possible, with safety and tolerability data. The totality of data collected on AC176 treatment may be ...