Intralesional Influenza Vaccine for the Treatment of Stage I-IV Melanoma

Metastatic Melanoma Clinical Trial

Official title:

Intralesional Influenza Vaccine for Patients With Melanoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04697576
• Other study ID #: OSU-20221
• Secondary ID: NCI-2020-13282
• Status: Recruiting
• Phase: Phase 1
• Start date: October 20, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: July 2023
• Source: Ohio State University Comprehensive Cancer Center
• Contact: The Ohio State University Comprehensive Cancer Center
• Phone: 800-293-5066
• Email: OSUCCCClinicaltrials[@]osumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase I trial investigates the effects of influenza vaccine in treating patients with stage I-IV melanoma. While intramuscular administration of influenza vaccine provides immunization against the influenza virus, giving influenza vaccine directly into the tumor (intralesional) may decrease the size of the injected melanoma tumor, or the extent of the melanoma within the body.

Description:

PRIMARY OBJECTIVE:

I. To evaluate the safety and tolerability and determine the maximum tolerated dose of intralesional (quadrivalent inactivated influenza vaccine (unadjuvanted influenza vaccine) for patients with a) resectable melanoma as monotherapy, and b) metastatic melanoma, concurrent with standard of care (single- or dual-agent) checkpoint inhibition.

SECONDARY OBJECTIVES:

I. To evaluate tumor dimensions of injected (Cohorts #1-2) and non-injected lesions (Cohort #2 only), by caliper or ultrasound measurement. (Clinical endpoint) II. To determine time to disease progression (local or distant). (Clinical endpoint) III. To evaluate immunohistochemistry density, cells/mm^2: CD4, CD8, PD-L1, PD1, CD56, CD20, CD45RO, FOXP3. (Tumor-based endpoint) IV. To evaluate granzyme B H-score. (Tumor-based endpoint) V. To evaluate NanoString Pan Cancer Immune Profiling Panel. (Tumor-based endpoint) VI. To evaluate tumor-infiltrating lymphocytes: not identified, present (non-brisk), present (brisk), cannot be determined. (Tumor-based endpoint) VII. To evaluate degree of tumor regression (percent). (Tumor-based endpoint) VIII. To evaluate changes in micro ribonucleic acid (microRNA) expression. (Tumor-based endpoint) IX. To evaluate of flow cytometry for T-cell subset evaluation and changes in circulating microRNA. (Blood draw endpoint)

EXPLORATORY OBJECTIVE:

I. To evaluate the evidence of immunologic activation in blood and tissue specimens.

OUTLINE: This is dose-escalation study. Patients are assigned to 1 of 2 cohorts.

COHORT I: Patients receive quadrivalent inactivated influenza vaccine intramuscularly (IM) on day 0 and intratumorally on days 2 and 14 in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery on day 28.

COHORT II: Patients receive quadrivalent inactivated influenza vaccine IM on day 0 and intratumorally on days 2, 14, 28, 42, 56, 70, 84, and 98 in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care ipilimumab, nivolumab, pembrolizumab, or Opdualag.

After completion of study treatment, patients are followed up for up to 1 year.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• 18 to 99 years of age

• Histologically confirmed cutaneous melanoma by historical pathology report review, clinical Stage I-III (Cohort #1), or Stage IV (Cohort #2) cutaneous melanoma

• At least one, biopsy-proven, palpable melanoma tumor deposit suitable for intralesional injection measuring = 1 cm by digital caliper (with digital photography documentation) or ultrasound (with ultrasound image documentation)

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1

Exclusion Criteria:

• Known allergy or intolerance to influenza vaccination

• Subjects with condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone/equivalent) or other immunosuppressive medications within 14 days of study drug administration

• Active, known or suspected autoimmune disease

• Active brain metastasis or leptomeningeal metastasis

• Diagnostic biopsy of ocular or mucosal melanoma

• Any melanoma therapy within 6 months of enrollment; though prior surgical resection is permitted

• Incarcerated patients

• Human immunodeficiency virus (HIV) positive patients

• Pregnant or lactating patients

• Patients incapable of independently providing consent

Related Conditions & MeSH terms

• Clinical Stage I Cutaneous Melanoma AJCC v8
• Clinical Stage IA Cutaneous Melanoma AJCC v8
• Clinical Stage IB Cutaneous Melanoma AJCC v8
• Clinical Stage II Cutaneous Melanoma AJCC v8
• Clinical Stage IIA Cutaneous Melanoma AJCC v8
• Clinical Stage IIB Cutaneous Melanoma AJCC v8
• Clinical Stage IIC Cutaneous Melanoma AJCC v8
• Clinical Stage IV Cutaneous Melanoma AJCC v8
• Melanoma
• Metastatic Melanoma
• Skin Neoplasms

Intervention

Biological:
• Ipilimumab
immune checkpoint inhibitor
• Nivolumab
immune checkpoint inhibitor
• Pembrolizumab
immune checkpoint inhibitor
• Quadrivalent Inactivated Influenza Vaccine
Given IM and intratumorally. For this protocol the U.S. F.D.A recently approved the use of recently expired influenza vaccine (only until new seasonal vaccine is available anticipated Sept 1). Use of expired vaccine will not exceed 4 months past June 30th expiry date (October 30th).

Procedure:
• Resection
Undergo surgical resection

Biological:
• Nivolumab + Relatlimab
immune checkpoint inhibitor

Locations

Country	Name	City	State
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Carlo Contreras

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events (AEs)	Frequency and severity of AEs and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. All patients who have received at least one dose of the therapeutic agents will be evaluable for toxicity and tolerability.	Up to 1 year after the last intra-tumoral dose
Primary	Maximum tolerated dose (MTD) in Cohorts #1 and #2	Will employ the Bayesian optimal interval design to find the MTD.	Up to 98 days
Secondary	Tumor dimensions of injected (Cohorts #1)	Will be assessed by caliper or ultrasound measurement. Tumor dimensions will be summarized using descriptive statistics (i.e. mean with standard deviations, or median with range).	Up to 1 year after the last intra-tumoral dose
Secondary	Tumor dimensions of non-injected lesions (Cohort #2)	Will be assessed by caliper or ultrasound measurement. Tumor dimensions will be summarized using descriptive statistics (i.e. mean with standard deviations, or median with range).	Up to 1 year after the last intra-tumoral dose
Secondary	Time to disease progression (local or distant)	Time to disease progression will be analyzed using Kaplan-Meier method, resulting in median survival times with 95% confidence interval, assuming sufficient events have occurred.	From the start of treatment until the documentation of local or distant disease progression, assessed up to 1 year
Secondary	Biomarker analysis	Will analyze immunohistochemistry density, cells/mm^2 of CD4, CD8, PD-L1, PD1, CD56, CD20, CD45RO, FOXP3. Summary statistics will be used.	Up to 1 year after the last intra-tumoral dose
Secondary	Granzyme B H-score	Summary statistics will be used.	Up to 1 year after the last intra-tumoral dose
Secondary	NanoString Pan Cancer Immune Profiling Panel	Summary statistics will be used.	Up to 1 year after the last intra-tumoral dose
Secondary	Tumor-infiltrating lymphocytes analysis	Will analyze tumor-infiltrating lymphocytes: not identified, present (non-brisk), present (brisk), cannot be determined. Summary statistics will be used.	Up to 1 year after the last intra-tumoral dose
Secondary	Degree of tumor regression (percent)	Summary statistics will be used.	Up to 1 year after the last intra-tumoral dose
Secondary	Changes in micro ribonucleic acid (RNA) expression	Summary statistics will be used.	Baseline up to 1 year after the last intra-tumoral dose
Secondary	T-cell subset evaluation and changes in circulating microRNA	Summary statistics will be used.	Up to 1 year after the last intra-tumoral dose

External Links

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