Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-26 @ 11:10 AM
Ignite Modification Date:
2025-12-26 @ 11:10 AM
NCT ID:
NCT03865212
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.
Detailed Description:
PRIMARY OBJECTIVE:
I. To determine the safety profile and maximum tolerated dose (MTD) of recombinant vesicular stomatitis virus-expressing interferon-beta and tyrosinase related protein 1 (VSV-IFNbeta-TYRP1) therapy when administered by intravenous (IV) and intratumoral (IT) injection in patients with previously treated metastatic melanoma.
SECONDARY OBJECTIVE:
I. To gather preliminary data on tumor response rate and progression-free survival time of VSV-IFNbeta-TYRP1 intravenous and intratumoral therapy among patients with metastatic malignant melanoma.
CORRELATIVE OBJECTIVES:
I. To determine the pharmacokinetic (PK) profile of VSV-IFNbeta-TYRP1 in patients by measurement of viremia in the blood using reverse transcriptase polymerase chain reaction (RT-PCR) for VSV-N ribonucleic acid (RNA).
II. To characterize the pharmacodynamics (PD) of VSV-IFNbeta-TYRP1 by measuring serum interferon-beta.
III. To determine if there is viral shedding (mouthwash, buccal swab, and urine) before and after viral treatment at different time points.
IV. Assess fresh pre- and post-treatment tumor biopsy samples for viral RNA, viral protein by immunohistochemistry (IHC), infectious virus recovery, infiltrating immune cells.
V. Assess transcriptome of fresh pre- and post-treatment tumor biopsy samples. VI. Assess exome of fresh peripheral blood lymphocytes (PBL) and fresh tumor samples pre-VSV treatment for neoantigen profiling.
VII. Assess changes in cytokine levels and immune cell profile in peripheral blood and tumor samples, pre and post viral treatment.
VIII. Assess if there is an increase in the amount of VSV and melanoma antigen, specifically TYRP1, reactive IFN-gamma secreting T cells by intracellular staining intracellular cytokine (ICS) and enzyme-linked immunosorbent spot (ELISpot) assays.
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 groups.
GROUP A: Patients receive recombinant vesicular stomatitis virus-expressing interferon-beta and tyrosinase related protein 1 intratumorally (IT) and intravenously (IV) over 30-60 minutes 2-4 hours later on day 1.
GROUP B: 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.
After completion of study treatment, patients in Group A are followed up at 42 days. Patients in Group B are followed up at 28 days, every 3 months until progressive disease, and then every 6 months for a maximum of 5 years after study registration.
Study:
NCT03865212
Study Brief:
Protocol Section:
NCT03865212