Modified Virus Therapy for Advanced Skin Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Immunosuppressants, Steroids, Anticoagulants, others

Disqualifiers: CNS metastases, Active infection, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days for Cycle 1, 21 days for subsequent cycles

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude those who need concurrent chemotherapy, immunotherapy, or certain other treatments. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment for advanced skin cancer?

Research shows that a virus similar to the one used in this treatment can selectively infect and kill melanoma cells, a type of skin cancer, while sparing normal cells. Additionally, combining this virus with other immune therapies has led to tumor shrinkage and enhanced immune responses in preclinical studies. ^{1 2 3 4 5}

Is the modified virus therapy for advanced skin cancer safe for humans?

The modified virus therapy, using vesicular stomatitis virus (VSV) expressing interferon-beta, has shown a good safety profile in preclinical studies, meaning it was generally safe in animal models. However, specific human safety data is not provided in the available research articles. ^{1 2 5 6 7}

How is the treatment for advanced skin cancer using a modified virus different from other treatments?

This treatment uses a modified virus that specifically targets and kills cancer cells while sparing normal cells, which is different from traditional therapies that can harm both. It combines a virus with interferon-beta and a protein related to skin pigment, aiming to boost the immune response against the cancer. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of a modified virus called VSV-IFNbetaTYRP1 in treating patients with stage III-IV melanoma. The vesicular stomatitis virus (VSV) has been altered to include two extra genes: human interferon beta (hIFNbeta), which may protect normal healthy cells from becoming infected with the virus, and TYRP1, which is expressed mainly in melanocytes (specialized skin cell that produces the protective skin-darkening pigment melanin) and melanoma tumor cells, and may trigger a strong immune response to kill the melanoma tumor cells.

Research Team

Roxana S. Dronca, M.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults over 18 with stage III-IV melanoma, including ocular melanoma. Participants must have tried FDA-approved systemic therapy and progressed after immune checkpoint inhibitors. For those with BRAF mutations, prior targeted therapies are needed. They should have at least one injectable tumor lesion and a life expectancy of 12+ weeks. Contraception use is required during the study and for 120 days after.

Inclusion Criteria

You have a detectable disease that can be seen on scans or imaging tests.

I have skin cancer that worsened after treatment with specific immune drugs.

Women who can have babies need to have a negative pregnancy test within 7 days before joining the study.

Exclusion Criteria

I have active skin issues, received vaccines for infections, and need blood thinners.

I have melanoma and a weakened immune system.

I have a history of tuberculosis, HIV, or hepatitis B/C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VSV-IFNbeta-TYRP1 intratumorally and intravenously. Cycle 1 continues for 28 days, with subsequent cycles repeating every 21 days.

28 days for Cycle 1, 21 days for subsequent cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment. Group A is followed up at 42 days, and Group B is followed up at 28 days, every 3 months until progressive disease, and then every 6 months for a maximum of 5 years.

Up to 5 years

Treatment Details

Interventions

• Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta and Tyrosinase Related Protein 1

Trial Overview The trial tests a modified virus called VSV-IFNbetaTYRP1 on patients with advanced melanoma to see if it's safe and what dose works best. The virus has been changed to include genes that might protect healthy cells and help the immune system attack melanoma cells.

Participant Groups

Group I: Group B (VSV-IFNbetaTYRP1) Experimental Treatment 1 Intervention

Patients receive recombinant vesicular stomatitis virus-expressing interferon-beta and tyrosinase related protein 1 IT and IV over 30-60 minutes 2-4 hours later on day 1. Cycle 1 continues for 28 days, with subsequent cycles repeating every 21 days in the absence of disease progression or unacceptable toxicity.

Group II: Group A (VSV-IFNbetaTYRP1) Experimental Treatment 1 Intervention

Patients receive recombinant vesicular stomatitis virus-expressing interferon-beta and tyrosinase related protein 1 IT and IV over 30-60 minutes 2-4 hours later 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]

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

Systemic combination virotherapy for melanoma with tumor antigen-expressing vesicular stomatitis virus and adoptive T-cell transfer. [2021]

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

Vesicular stomatitis virus variants selectively infect and kill human melanomas but not normal melanocytes. [2021]

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

Combination viroimmunotherapy with checkpoint inhibition to treat glioma, based on location-specific tumor profiling. [2022]

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

Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma. [2021]