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Intralesional Influenza Vaccine for the Treatment of Stage I, II, and IV Melanoma

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ClinicalTrials.gov Identifier: NCT04697576
Recruitment Status : Recruiting
First Posted : January 6, 2021
Last Update Posted : September 20, 2021
Sponsor:
Information provided by (Responsible Party):
Carlo Contreras, Ohio State University Comprehensive Cancer Center

Study Description
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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
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 Metastatic Melanoma Biological: Ipilimumab Biological: Nivolumab Biological: Pembrolizumab Biological: Quadrivalent Inactivated Influenza Vaccine Procedure: Resection Phase 1

Detailed 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-agent checkpoint inhibition.

SECONDARY OBJECTIVES:

I. 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) 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, or pembrolizumab.

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intralesional Influenza Vaccine for Patients With Melanoma
Estimated Study Start Date : November 1, 2021
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma

Arms and Interventions
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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:
  • Fluzone Quadrivalent
  • Fluzone Quadrivalent Influenza Vaccine
  • QIV
  • Quadrivalent Influenza Vaccine

Procedure: Resection
Undergo surgical resection
Other Name: Surgical Resection
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:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Biological: Nivolumab
immune checkpoint inhibitor
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Biological: Pembrolizumab
immune checkpoint inhibitor
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Biological: Quadrivalent Inactivated Influenza Vaccine
Given IM and intratumorally
Other Names:
  • Fluzone Quadrivalent
  • Fluzone Quadrivalent Influenza Vaccine
  • QIV
  • Quadrivalent Influenza Vaccine


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of adverse events (AEs) [ Time Frame: 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.

  2. Maximum tolerated dose (MTD) in Cohorts #1 and #2 [ Time Frame: Up to 98 days ]
    Will employ the Bayesian optimal interval design to find the MTD.


Secondary Outcome Measures :
  1. Tumor dimensions of injected (Cohorts #1) [ Time Frame: 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).

  2. Tumor dimensions of non-injected lesions (Cohort #2) [ Time Frame: 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).

  3. Time to disease progression (local or distant) [ Time Frame: 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.

  4. Biomarker analysis [ Time Frame: 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.

  5. Granzyme B H-score [ Time Frame: Up to 1 year after the last intra-tumoral dose ]
    Summary statistics will be used.

  6. NanoString Pan Cancer Immune Profiling Panel [ Time Frame: Up to 1 year after the last intra-tumoral dose ]
    Summary statistics will be used.

  7. Tumor-infiltrating lymphocytes analysis [ Time Frame: 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.

  8. Degree of tumor regression (percent) [ Time Frame: Up to 1 year after the last intra-tumoral dose ]
    Summary statistics will be used.

  9. Changes in micro ribonucleic acid (RNA) expression [ Time Frame: Baseline up to 1 year after the last intra-tumoral dose ]
    Summary statistics will be used.

  10. T-cell subset evaluation and changes in circulating microRNA [ Time Frame: Up to 1 year after the last intra-tumoral dose ]
    Summary statistics will be used.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • At least one, biopsy-proven, palpable melanoma tumor deposit suitable for intralesional injection measuring >= 1 cm
  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04697576


Contacts
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Contact: The Ohio State University Comprehensive Cancer Center 800-293-5066 OSUCCCClinicaltrials@osumc.edu

Locations
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United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Carlo M. Contreras, MD    614-366-3681    Carlo.Contreras@osumc.edu   
Principal Investigator: Carlo M. Contreras, MD         
Sponsors and Collaborators
Carlo Contreras
Investigators
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Principal Investigator: Carlo M Contreras, MD Ohio State University Comprehensive Cancer Center
More Information
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Additional Information:

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Responsible Party: Carlo Contreras, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT04697576    
Other Study ID Numbers: OSU-20221
NCI-2020-13282 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: January 6, 2021    Key Record Dates
Last Update Posted: September 20, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Melanoma
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms by Site
Skin Diseases
 Pembrolizumab
Nivolumab
Ipilimumab
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action