Modified Virus VSV-IFNbetaTYRP1 in Treating Patients With Stage III-IV Melanoma

NCT03865212 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: MC1376NCI-2019-0112718-000991
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Choroid Melanoma; Metastatic Melanoma; Metastatic Mucosal Melanoma; Metastatic Uveal Melanoma; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Unresectable Melanoma

Outcome Measures

Primary Outcomes (2)

• Maximum-tolerated dose

  The maximum tolerated dose is defined as the highest dose level among those tested where at most 1 out of 6 patients develops a dose-limiting toxicity (DLT) prior to the start of their second cycle of treatment and the next highest dose level is such that 2 of the 3 to 6 patients treated at this dose level develop a DLT prior to the start of their second cycle of treatment.

  Up to 28 days

• Incidence of adverse events

  Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed by dose level to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

  Up to 42 days after treatment for Group A and 28 days after treatment for Group B

Secondary Outcomes (2)

• Tumor response rate

  Up to 1 year

• Overall survival

  From registration to death due to any cause, assessed up to 1 year

Study Arms (2)

Group A (VSV-IFNbetaTYRP1)

EXPERIMENTAL

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.

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

Group B (VSV-IFNbetaTYRP1)

EXPERIMENTAL

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.

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

Interventions

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

Given IT and IV

Also known as: Recombinant VSV-expressing IFN-b and TYRP1, Recombinant VSV-IFNbetaTYRP1, VSV-IFN-b/TYRP1, VSV-IFNbetaTYRP1

Group A (VSV-IFNbetaTYRP1); Group B (VSV-IFNbetaTYRP1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years
• Histologically or cytologically confirmed diagnosis of unresectable stage III or metastatic (stage IV) melanoma, including metastatic ocular melanoma
• Cutaneous melanoma patients only:
• At least one prior Food and Drug Administration (FDA) approved systemic therapy in the metastatic setting; and disease progression after immune checkpoint inhibitors
• If tumor is BRAF-mutated, previous BRAF- and/or MEK-targeted therapies are required
• NOTE: for ocular melanoma patients no current standard of care exists, so patients are permitted to be treated in 1st line setting
• Measurable disease by any imaging modality as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1)
• NOTE: disease that is measurable by physical examination only is not eligible
• Injectable disease (i.e., suitable for direct injection or through the use of ultrasound guidance) defined as:
• At least 1 injectable and safely accessible cutaneous, subcutaneous, or nodal melanoma lesion \>= 5 mm in longest diameter for metastatic cutaneous or mucosal melanoma
• At least one safely accessible liver metastasis for patients with metastatic ocular melanoma
• No more than 25% overall tumor involvement of the liver by magnetic resonance imaging (MRI) imaging
• Child Pugh Score A
• Absence of ascites
• No portal vein thrombosis

You may not qualify if:

• Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
• Any of the following prior therapies:
• Prior chemotherapy =\< 2 weeks prior to registration
• Prior immunotherapy (monoclonal antibodies) =\< 3 weeks prior to registration
• Prior experimental agent =\< 2 weeks prior to registration
• Prior radiation therapy =\< 2 weeks prior to registration
• Need for concurrent chemotherapy, immunotherapy, radiotherapy, ablation therapy or any ancillary therapy considered investigational (used for a non-FDA approved indication or in the context of a research investigation)
• Minor surgical or interventional procedure =\< 7 days prior to registration
• Major surgical procedure =\< 21 days prior to registration
• History or evidence of melanoma associated with immunodeficiency states (e.g., hereditary immune deficiency, organ transplant, or leukemia, requires concomitant treatment with immunosuppressive agents, including CTLA-4 agonists, or chronic oral or systemic steroid medication including physiological replacement doses for adrenal insufficiency
• History of or plan for splenectomy or splenic irradiation
• History or evidence of central nervous system (CNS) metastases
• Active skin lesions (open wounds, severe rash, herpetic lesions, etc.)
• Prior non-oncology vaccine therapies used for the prevention of infectious disease =\< 28 days prior to registration
• Requires concomitant treatment with therapeutic anticoagulants

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (2)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Uveal Melanoma; Melanoma

Interventions

TYRP1 protein, human

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Roxana S. Dronca, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2019
• First Posted: March 6, 2019
• Study Start: June 12, 2019
• Primary Completion: October 12, 2025
• Study Completion: October 12, 2025
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

US (2)