Intralesional Influenza Vaccine for the Treatment of Stage I, II, and IV Melanoma
Study Details
Study Description
Brief Summary
This phase I trial investigates the effects of influenza vaccine in treating patients with stage I, II, and 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
Phase 1 |
Detailed Description
PRIMARY OBJECTIVE:
- 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-agent checkpoint inhibition.
SECONDARY OBJECTIVES:
- To evaluate tumor dimensions of injected (Cohorts #1-2) and non-injected lesions (Cohort #2 only), by caliper 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)
- 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:
- 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, or pembrolizumab.
After completion of study treatment, patients are followed up for up to 1 year.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort I (quadrivalent inactivated influenza vaccine) Patients receive influenza vaccine 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. |
Biological: Quadrivalent Inactivated Influenza Vaccine
Given IM and intratumorally
Other Names:
Procedure: Resection
Undergo surgical resection
Other Names:
|
| Experimental: Cohort II (quadrivalent inactivated influenza vaccine) Patients receive 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, or pembrolizumab. |
Biological: Ipilimumab
immune checkpoint inhibitor
Other Names:
Biological: Nivolumab
immune checkpoint inhibitor
Other Names:
Biological: Pembrolizumab
immune checkpoint inhibitor
Other Names:
Biological: Quadrivalent Inactivated Influenza Vaccine
Given IM and intratumorally
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence of adverse events (AEs) [Up to 1 year after the last intra-tumoral dose]
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.
- Maximum tolerated dose (MTD) in Cohorts #1 and #2 [Up to 98 days]
Will employ the Bayesian optimal interval design to find the MTD.
Secondary Outcome Measures
- Tumor dimensions of injected (Cohorts #1) [Up to 1 year after the last intra-tumoral dose]
Will be assessed by caliper measurement. Tumor dimensions will be summarized using descriptive statistics (i.e. mean with standard deviations, or median with range).
- Tumor dimensions of non-injected lesions (Cohort #2) [Up to 1 year after the last intra-tumoral dose]
Will be assessed by caliper measurement. Tumor dimensions will be summarized using descriptive statistics (i.e. mean with standard deviations, or median with range).
- Time to disease progression (local or distant) [From the start of treatment until the documentation of local or distant disease progression, assessed up to 1 year]
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.
- Biomarker analysis [Up to 1 year after the last intra-tumoral dose]
Will analyze immunohistochemistry density, cells/mm^2 of CD4, CD8, PD-L1, PD1, CD56, CD20, CD45RO, FOXP3. Summary statistics will be used.
- Granzyme B H-score [Up to 1 year after the last intra-tumoral dose]
Summary statistics will be used.
- NanoString Pan Cancer Immune Profiling Panel [Up to 1 year after the last intra-tumoral dose]
Summary statistics will be used.
- Tumor-infiltrating lymphocytes analysis [Up to 1 year after the last intra-tumoral dose]
Will analyze tumor-infiltrating lymphocytes: not identified, present (non-brisk), present (brisk), cannot be determined. Summary statistics will be used.
- Degree of tumor regression (percent) [Up to 1 year after the last intra-tumoral dose]
Summary statistics will be used.
- Changes in micro ribonucleic acid (RNA) expression [Baseline up to 1 year after the last intra-tumoral dose]
Summary statistics will be used.
- T-cell subset evaluation and changes in circulating microRNA [Up to 1 year after the last intra-tumoral dose]
Summary statistics will be used.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
18 to 90 years of age
-
Histologically confirmed cutaneous melanoma, clinical stage I/II (Cohort #1), or stage IV (Cohort #2) cutaneous melanoma
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At least one, biopsy-proven, palpable melanoma tumor deposit suitable for intralesional injection measuring >= 1 cm
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
Exclusion Criteria:
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Known allergy or intolerance to influenza vaccination
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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
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Active, known or suspected autoimmune disease
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Active brain metastasis or leptomeningeal metastasis
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Diagnostic biopsy of ocular or mucosal melanoma
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Any melanoma therapy within 6 months of enrollment; though prior surgical resection is permitted
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Incarcerated patients
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Human immunodeficiency virus (HIV) positive patients
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Pregnant or lactating patients
-
Patients incapable of independently providing consent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ohio State University Comprehensive Cancer Center | Columbus | Ohio | United States | 43210 |
Sponsors and Collaborators
- Carlo Contreras
Investigators
- Principal Investigator: Carlo M Contreras, MD, Ohio State University Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- OSU-20221
- NCI-2020-13282