AU409 for Liver Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Anthony El-Khoueiry, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Southern California

Must not be taking: Warfarin, Strong P450 inducers/inhibitors

Disqualifiers: CNS metastases, Heart failure, Active infection, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests AU409, a new drug, in patients with advanced liver cancers or solid tumors that have spread to the liver. AU409 aims to stop cancer cells from growing and spreading. Researchers are checking if it is safe and effective.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking medications that are strong inducers or inhibitors of the cytochrome P450 enzymes at least one week before starting the treatment and during the trial. If these medications are essential and cannot be replaced, you may still be considered for enrollment after discussing with the principal investigator.

What data supports the effectiveness of the drug AU409 for liver cancer?

Research shows that a similar drug, sorafenib, significantly improved survival in patients with advanced liver cancer. Sorafenib, when combined with another drug called doxorubicin, also showed potential in improving survival outcomes. ^{1 2 3 4 5}

How does the drug AU409 differ from other liver cancer treatments?

AU409 is unique because it involves microRNA-409, which can down-regulate the Jak-Stat pathway, a process that may inhibit the progression of liver cancer. This mechanism is different from traditional treatments that often focus on directly targeting cancer cells or boosting the immune system. ^{6 7 8 9 10}

Research Team

Anthony El-Khoueiry, MD

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for adults with advanced primary liver cancers or solid tumors that have spread to the liver. Participants must have tried all standard treatments, be in good physical condition (ECOG 0-1), and not be pregnant or breastfeeding. They should also meet specific blood count and organ function criteria, agree to use contraception, and not have certain medical conditions like active infections or recent heart issues.

Inclusion Criteria

I am 18 years old or older.

I finished any cancer treatments at least 4 weeks ago.

I have recovered from side effects of my previous cancer treatments.

Exclusion Criteria

My liver cancer is advanced with a moderate to severe impact on my health.

I haven't had cancer treatment in the last 28 days.

I am taking medication that strongly affects liver enzymes.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Treatment

Patients receive AU409 orally to determine the maximum tolerated dose and recommended phase II dose. Patients also undergo CT or MRI and collection of blood samples throughout the trial.

28 days

Multiple visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and pharmacokinetics.

Up to 30 days after treatment

Long-term Follow-up

Participants are monitored for objective radiologic response and long-term safety.

Up to 3 years

Treatment Details

Interventions

• AU-409 (RNA Transcription Modulator)

Trial Overview The trial tests AU409's safety, side effects, and optimal dosage on patients with advanced liver cancer or those whose solid tumors have metastasized to the liver. It aims to find out if AU409 can halt cancer growth and spread by collecting biospecimens and using imaging techniques like CT scans and MRIs.

Participant Groups

Group I: Treatment (AU409) Experimental Treatment 4 Interventions

Patients receive AU409 PO on study. Patients also undergo CT or MRI and collection of blood samples throughout the trial.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

USC / Norris Comprehensive Cancer Center Los Angeles, CA

Los Angeles County-USC Medical Center Los Angeles, CA

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Dr. Samir A.

University of Southern California

Chief Executive Officer since 2024

PhD in Molecular Biology from the University of Southern California

Dr. Chung

University of Southern California

Chief Medical Officer since 2016

MD from UC San Diego

National Cancer Institute (NCI)

Collaborator

Trials

14080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Auransa, Inc.

Collaborator

Trials

1

Recruited

40+

Findings from Research

In a study of 1158 patients with recurrent hepatocellular carcinoma (HCC), the time-to-interventional failure (TIF) was found to be a better predictor of overall survival (OS) than recurrence-free survival (RFS), with a correlation coefficient of 0.921 compared to 0.631.

Patients receiving aggressive curative treatments for recurrence, such as resection or ablation, had significantly better survival outcomes (median OS of 89.1 months) compared to those receiving non-curative treatments (median OS of 55.0 months), indicating the importance of treatment type in improving survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-to-Interventional Failure as a New Surrogate Measure for Survival Outcomes after Resection of Hepatocellular Carcinoma. Shindoh, J., Kawamura, Y., Kobayashi, Y., et al.[2021]

MicroRNA-409 levels are significantly lower in liver cancer tissues compared to normal and paracancerous tissues, and its expression is negatively correlated with tumor stage and patient survival, suggesting it plays a critical role in liver cancer progression.

Overexpressing microRNA-409 in liver cancer cells reduces cell viability and promotes apoptosis by down-regulating the Jak-Stat signaling pathway, indicating its potential as a therapeutic target for inhibiting liver cancer growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

miR-409 down-regulates Jak-Stat pathway to inhibit progression of liver cancer. Zhang, CS., Lin, Y., Sun, FB., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Treatment of primary liver cancer. [2013]

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

Assessment of Treatment With Sorafenib Plus Doxorubicin vs Sorafenib Alone in Patients With Advanced Hepatocellular Carcinoma: Phase 3 CALGB 80802 Randomized Clinical Trial. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Sorafenib: in hepatocellular carcinoma. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Treatment stage migration and treatment sequences in patients with hepatocellular carcinoma: drawbacks and opportunities. [2021]

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

Time-to-Interventional Failure as a New Surrogate Measure for Survival Outcomes after Resection of Hepatocellular Carcinoma. [2021]

6. Italy pubmed.ncbi.nlm.nih.gov

miR-409 down-regulates Jak-Stat pathway to inhibit progression of liver cancer. [2020]

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

CD40ligand-expressing dendritic cells induce regression of hepatocellular carcinoma by activating innate and acquired immunity in vivo. [2022]

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

The clinical significance of microRNA-409 in pancreatic carcinoma and associated tumor cellular functions. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Alpha-Fetoprotein- and CD40Ligand-Expressing Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma. [2021]

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

Adenovirus-mediated CD40 ligand gene therapy in a rat model of orthotopic hepatocellular carcinoma. [2020]