- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04697576
Intralesional Influenza Vaccine for the Treatment of Stage I-IV Melanoma
Intralesional Influenza Vaccine for Patients With Melanoma
Study Overview
Status
Conditions
- Metastatic Melanoma
- 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
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- 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.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: The Ohio State University Comprehensive Cancer Center
- Phone Number: 800-293-5066
- Email: OSUCCCClinicaltrials@osumc.edu
Study Locations
-
-
Ohio
-
Columbus, Ohio, United States, 43210
- Recruiting
- Ohio State University Comprehensive Cancer Center
-
Contact:
- Carlo M. Contreras, MD
- Phone Number: 614-366-3681
- Email: Carlo.Contreras@osumc.edu
-
Principal Investigator:
- Carlo M. Contreras, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort I (resectable Stage I-III melanoma)
Patients receive an 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.
|
Undergo surgical resection
Other Names:
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).
Other Names:
|
Experimental: Cohort II (unresectable Stage IV)
Patients receive an 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 (single- or dual-agent) ipilimumab, nivolumab, relatlimab, or pembrolizumab.
|
immune checkpoint inhibitor
Other Names:
immune checkpoint inhibitor
Other Names:
immune checkpoint inhibitor
Other Names:
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).
Other Names:
immune checkpoint inhibitor
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 1 year after the last intra-tumoral dose
|
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.
|
Up to 98 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
From the start of treatment until the documentation of local or distant disease progression, assessed up to 1 year
|
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.
|
Up to 1 year after the last intra-tumoral dose
|
Granzyme B H-score
Time Frame: Up to 1 year after the last intra-tumoral dose
|
Summary statistics will be used.
|
Up to 1 year after the last intra-tumoral dose
|
NanoString Pan Cancer Immune Profiling Panel
Time Frame: Up to 1 year after the last intra-tumoral dose
|
Summary statistics will be used.
|
Up to 1 year after the last intra-tumoral dose
|
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.
|
Up to 1 year after the last intra-tumoral dose
|
Degree of tumor regression (percent)
Time Frame: Up to 1 year after the last intra-tumoral dose
|
Summary statistics will be used.
|
Up to 1 year after the last intra-tumoral dose
|
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.
|
Baseline up to 1 year after the last intra-tumoral dose
|
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.
|
Up to 1 year after the last intra-tumoral dose
|
Tumor dimensions of injected (Cohorts #1)
Time Frame: Up to 1 year after the last intra-tumoral dose
|
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
|
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 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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Carlo M Contreras, MD, Ohio State University Comprehensive Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Skin Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Vaccines
- Nivolumab
- Pembrolizumab
- Ipilimumab
- Relatlimab
Other Study ID Numbers
- OSU-20221
- NCI-2020-13282 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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