Modified Virus Therapy for Advanced Skin Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a modified virus treatment for individuals with advanced melanoma, a type of skin cancer. The virus, known as Recombinant Vesicular Stomatitis Virus-expressing Interferon-beta and Tyrosinase Related Protein 1, has been altered to include genes that may protect healthy cells and stimulate the immune system to attack cancer cells. The trial aims to determine the best dose and identify any side effects. Individuals with advanced melanoma that has spread or cannot be surgically removed, and who have tried at least one other FDA-approved treatment, might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research has shown that the modified virus treatment, VSV-IFNbetaTYRP1, can be safely administered to patients. In earlier studies, researchers delivered this virus directly into the tumor and through a vein to individuals previously treated for melanoma. The treatment was well-tolerated, with patients not experiencing severe side effects. While some side effects may occur, they were usually mild. This suggests that the treatment is generally safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for melanoma?

Most treatments for advanced skin cancer, like chemotherapy and immunotherapy, work by directly targeting cancer cells or boosting the immune system's natural response. But this new therapy uses a modified virus, specifically the recombinant vesicular stomatitis virus, to deliver interferon-beta and tyrosinase related protein 1 directly into the cancer cells. This unique mechanism allows the virus to selectively infect and kill cancer cells while sparing healthy ones. Researchers are excited because this approach not only targets cancer cells more precisely but also potentially reduces side effects compared to conventional treatments. Plus, it taps into the body's own defenses by using interferon-beta to boost the immune response against the cancer.

What evidence suggests that this treatment might be an effective treatment for advanced skin cancer?

Research has shown that VSV-IFNbetaTYRP1 is a promising treatment for advanced skin cancer, such as melanoma. This modified virus targets cancer cells and aids the immune system in attacking them. Studies have demonstrated that it can be safely administered to patients and specifically multiplies in cancer cells, leaving healthy ones unharmed. The virus contains two special components: one that boosts the immune system (interferon-beta) and another that targets melanoma cells (TYRP1). In this trial, participants will be assigned to different groups to receive VSV-IFNbetaTYRP1. These early findings suggest that VSV-IFNbetaTYRP1 could effectively combat melanoma by strengthening the body's natural defenses. ^{1 2 3 4 5}

Who Is on the Research Team?

Roxana S. Dronca, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03865212

Modified Virus VSV-IFNbetaTYRP1 in Treating Patients ... 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.

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38022659/

A phase I oncolytic virus trial with vesicular stomatitis virus ... Our study found that VSV-IFNβ -TYRP1 can be safely administered via intratumoral (IT) and IV routes in a previously treated population of patients with MUM.

4. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/797080

recombinant vesicular stomatitis virus-expressing ... Upon intratumoral and intravenous administration, recombinant VSV-expressing IFN-b/TYRP1 preferentially replicates in tumor cells. Due to defective IFN-b- ...

5. researchgate.net researchgate.net/publication/375137146_A_phase_I_oncolytic_virus_trial_with_vesicular_stomatitis_virus_expressing_human_interferon_beta_and_tyrosinase_related_protein_1_administered_intratumorally_and_intravenously_in_uveal_melanoma_safety

(PDF) A phase I oncolytic virus trial with vesicular stomatitis ... Our study found that VSV-IFNβ -TYRP1 can be safely administered via intratumoral (IT) and IV routes in a previously treated population of patients with MUM.