Viral Therapy for Liver Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Corticosteroids, Chemotherapy

Disqualifiers: HIV, Transplant history, Uncontrolled infection, others

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

Compensation: Varies

Number of Visits: 5

Duration: 1 day

17 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop any systemic anti-cancer therapy at least 4 weeks before joining and any corticosteroid use at least 28 days before joining. Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy is not allowed during the trial.

What data supports the effectiveness of the treatment Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta for liver cancer?

Research shows that a similar virus treatment was effective in rats with advanced liver cancer, leading to improved survival and some cases of complete tumor removal without harming the liver. ^{1 2 3 4 5}

How is the treatment for liver cancer using recombinant VSV-IFN-β different from other treatments?

This treatment uses a virus that specifically targets and destroys cancer cells in the liver without harming normal cells, making it unique compared to traditional therapies. It is administered directly into the liver's blood supply, allowing for targeted action and reduced side effects. ^{1 2 5 6 7}

What is the purpose of this trial?

This phase I trial studies the best dose and side effects of recombinant vesicular stomatitis virus expressing interferon beta in treating patients with liver cancer or solid tumors with lesions that have spread to other parts of the body and do not respond to treatment. The study virus has a gene inserted into it which will allow production of interferon beta, which is a substance that will restrict the spread of the virus to tumor cells and not healthy cells. It will also have some independent anti-cancer activity. Although the primary goal of this study is to evaluate the safety of delivery of this viral agent to people, patients may benefit clinically by having shrinkage or stabilization of their tumor or reduction in their cancer related symptoms (e.g., pain). Funding Source - FDA OOPD.

Research Team

Mitesh Borad, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults with advanced liver cancer or solid tumors that have spread and are not responding to treatment. Participants must meet specific health criteria like certain blood cell counts, liver function tests, and life expectancy of at least 12 weeks. Pregnant women, those with organ transplants, uncontrolled infections, HIV, or recent corticosteroid use cannot join.

Inclusion Criteria

ARM A: INR =< 1.5 x ULN

ARM A: aPTT =< 1.5 x ULN

ARM A: Life expectancy >= 12 weeks

Exclusion Criteria

ARM A: Uncontrolled infection

I am not receiving any other cancer treatments.

ARM B: Any condition, which in the opinion of the investigator would render the patient unsuitable to participate in the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally on day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Every 4 weeks

Treatment Details

Interventions

• Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta

Trial Overview The trial is testing a genetically modified virus designed to target cancer cells without harming healthy ones. It carries a gene for interferon beta which may help control the tumor's growth. The study aims to find the safest dose while observing any potential benefits such as tumor shrinkage.

Participant Groups

Group I: Arm B (viral therapy in multiple locations) Experimental Treatment 3 Interventions

Patients with advanced solid tumor with subcutaneous/cutaneous lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in up to 5 cutaneous, subcutaneous, or soft tissue tumor lesions on day 1.

Group II: Arm A (viral therapy in single tumor location) Experimental Treatment 3 Interventions

Patients with hepatocellular carcinoma or advanced solid tumor with liver lesions receive recombinant vesicular stomatitis virus expressing interferon beta intratumorally in a single tumor location on day 1.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

VSV-IFN-β, a recombinant virus expressing interferon-β, showed significant antitumor activity in preclinical studies with syngeneic squamous cell carcinoma models, demonstrating both safety and efficacy in immunocompetent rats.

The treatment did not cause acute organ toxicity or death, and both intratumoral and intravenous administration of VSV-IFN-β led to tumor growth delay and improved survival, supporting its potential for clinical testing in human head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical safety and activity of recombinant VSV-IFN-β in an immunocompetent model of squamous cell carcinoma of the head and neck. Kurisetty, VV., Heiber, J., Myers, R., et al.[2021]

Vesicular stomatitis virus encoding interferon β (VSV-IFNβ) shows promising efficacy in preclinical cancer models, with 37 out of 42 experiments reporting positive outcomes across various administration routes.

Despite the encouraging results, further research is needed to confirm the safety and efficacy of VSV-IFNβ before it can be translated into clinical trials, as some studies did report negative outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical efficacy of oncolytic VSV-IFNβ in treating cancer: A systematic review. Moglan, AM., Albaradie, OA., Alsayegh, FF., et al.[2023]

Genetically engineered vesicular stomatitis virus (VSV-IFNbeta) can selectively target and kill cancer cells while sparing normal cells, due to its ability to exploit defects in the interferon (IFN) response in transformed cells.

VSV-IFNbeta not only shows reduced growth in normal cells due to the production of recombinant IFN-beta, but also retains strong oncolytic activity against metastatic lung cancer in mice, generating effective antitumor immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of recombinant vesicular stomatitis viruses that exploit defects in host defense to augment specific oncolytic activity. Obuchi, M., Fernandez, M., Barber, GN.[2020]

References

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

Preclinical safety and activity of recombinant VSV-IFN-β in an immunocompetent model of squamous cell carcinoma of the head and neck. [2021]

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

Preclinical efficacy of oncolytic VSV-IFNβ in treating cancer: A systematic review. [2023]

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

Enhanced oncolytic activity of vesicular stomatitis virus encoding SV5-F protein against prostate cancer. [2010]

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

Development of recombinant vesicular stomatitis viruses that exploit defects in host defense to augment specific oncolytic activity. [2020]

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

Eradication of advanced hepatocellular carcinoma in rats via repeated hepatic arterial infusions of recombinant VSV. [2012]

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

Syncytia induction enhances the oncolytic potential of vesicular stomatitis virus in virotherapy for cancer. [2022]

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

Oncolysis of multifocal hepatocellular carcinoma in the rat liver by hepatic artery infusion of vesicular stomatitis virus. [2022]