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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the safety of a new viral treatment for liver cancer and other solid tumors that have spread and resist current treatments. The treatment employs a virus specifically designed to target cancer cells while sparing healthy ones, potentially reducing tumor size or alleviating symptoms like pain. Suitable candidates have liver cancer or solid tumors unresponsive to standard treatments, with their condition worsening despite these efforts. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

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

Research shows that a new treatment, VSV-IFN-β, has demonstrated promising results in early studies. Lab studies have shown that this virus can effectively target and destroy various cancer cells, including those in liver cancer and other tumors.

Regarding safety, these early studies suggest that VSV-IFN-β is generally well-tolerated. As a Phase 1 trial, the treatment is still in the early stages of human testing. The main goal is to find the safest dose and identify any side effects. While lab results are encouraging, human trials are essential to confirm these findings. Participants in this trial will help researchers understand how well people handle the treatment and what side effects might occur. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the recombinant vesicular stomatitis virus-expressing interferon-beta because it offers a novel approach to treating liver cancer. Unlike traditional treatments like surgery, chemotherapy, or targeted therapies, this viral therapy directly targets tumors by delivering a virus that expresses interferon-beta, an immune system booster, right into the tumor tissue. This method not only aims to destroy cancer cells but also to stimulate the body's immune response against the cancer. Additionally, the administration of the virus directly into the tumor site might reduce side effects typically associated with systemic cancer therapies.

What evidence suggests that this viral therapy could be effective for liver cancer?

Research has shown that a modified virus, called recombinant vesicular stomatitis virus, may help treat liver cancer and other solid tumors. In early studies, this virus found and destroyed various cancer cells, including those in the liver, while leaving healthy cells unharmed. Out of 42 tests, 37 yielded positive results, indicating high effectiveness. The virus also reduced tumor size and improved survival rates in animal studies, particularly for liver cancer. Additionally, the virus produces a substance called interferon-beta, which might enhance the body's immune response against cancer.

In this trial, participants will receive the viral therapy in one of two ways: Arm A administers the therapy to a single tumor location, while Arm B administers it to multiple tumor locations. These findings suggest that this treatment could help shrink tumors or stabilize cancer in patients. ^{2 3 4 5 6}

Who Is on the Research Team?

Mitesh Borad, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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

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

I am not receiving any other cancer treatments.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01628640

Study Details | NCT01628640 | Viral Therapy in Treating ... This phase I trial studies the best dose and side effects of recombinant vesicular stomatitis virus expressing interferon beta in treating patients with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10644866/

A phase I oncolytic virus trial with vesicular stomatitis ... We developed an OV with a Vesicular Stomatitis Virus (VSV) vector modified to express interferon-beta (IFN-β) and Tyrosinase Related Protein 1 (TYRP1)

3. withpower.com withpower.com/trial/phase-1-carcinoma-7-2012-88d81

Viral Therapy for Liver Cancer · Info for Participants Vesicular stomatitis virus encoding interferon β (VSV-IFNβ) shows promising efficacy in preclinical cancer models, with 37 out of 42 experiments reporting ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1044532325000685

Latest insights into oncolytic viro-immunotherapy with ... Vesicular stomatitis virus (VSV), a rhabdovirus with intrinsic oncolytic properties, has emerged as a promising candidate for cancer therapy.

5. oncotarget.com oncotarget.com/article/5320/text/

Vesicular stomatitis virus expressing interferon-β is ... VSV that produces interferon-β (VSV-IFNβ) is now in early clinical testing for solid tumors. Here, the preclinical activity of VSV and VSV-IFNβ ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3969865/

PRECLINICAL SAFETY AND ACTIVITY OF ... VSV-IFN-β, a recombinant vesicular stomatitis virus expressing interferon-β, has demonstrated antitumor activity in vitro and in vivo.