AC176 for Prostate Cancer

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

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing AC176, a new drug, in patients with advanced prostate cancer that hasn't responded to other treatments. The drug works by breaking down a protein that helps the cancer grow.

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.

What data supports the effectiveness of the drug AC176 for prostate cancer?

Research on apalutamide, a component similar to AC176, shows it improves survival and delays cancer progression in prostate cancer patients when combined with hormone therapy. This suggests that AC176 might also be effective in treating prostate cancer. ^{1 2 3 4 5}

What safety data exists for AC176 (apalutamide) in humans?

Apalutamide, also known as AC176, has been associated with side effects like skin reactions, fatigue, falls, fractures, and rash in prostate cancer patients. These side effects sometimes require adjusting the dose or interrupting treatment. ^{6 7 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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]

References

1. England 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. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Pre-existing Castration-resistant Prostate Cancer-like Cells in Primary Prostate Cancer Promote Resistance to Hormonal Therapy. [2023]

3. Switzerland 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. [2023]

5. Netherlands 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Real-world prostate-specific antigen response and progression to castration-resistant prostate cancer among men with metastatic castration-sensitive prostate cancer treated with apalutamide: a multi-institutional study in the Chu-shikoku Japan Urological Consortium. [2023]

7. England 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. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Lin28 induces resistance to anti-androgens via promotion of AR splice variant generation. [2021]

9. United States 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. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Endocrine consequences of treatment with the new androgen receptor axis-targeted agents for advanced prostate cancer. [2021]