Ignite Creation Date:
2024-05-06 @ 12:50 PM
Last Modification Date:
2024-10-26 @ 1:05 PM
Study NCT ID:
NCT03865212
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-01-09
First Post:
2019-03-04
Brief Title:
Modified Virus VSV-IFNbetaTYRP1 in Treating Patients With Stage III-IV Melanoma
Sponsor:
Mayo Clinic
Organization:
Mayo Clinic
Study Overview
Official Title:
Phase I Trial to Evaluate the Safety and Efficacy of Intratumoral and Intravenous Injection of Vesicular Stomatitis Virus Expressing Human Interferon Beta and Tyrosinase Related Protein 1 VSV-IFNb-TYRP1 in Patients With Metastatic Ocular Melanoma and Previously Treated Patients With Unresectable Stage IIIIV Cutaneous Melanoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2019-01127 | REGISTRY | None | None |
| MC1376 | OTHER | None | None |
| 18-000991 | OTHER | Mayo Clinic Institutional Review Board | None |