Clinical trial NCT04697576: Intralesional Influenza Vaccine for the Treatment of Stage I-IV Melanoma
Official title: Intralesional Influenza Vaccine for Patients with Melanoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: 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
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2021-01-06
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Up to 1 year after the last intra-tumoral dose
measure: Maximum tolerated dose (MTD) in Cohorts #1 and #2
timeFrame: Up to 98 days
Secondary outcomes:
measure: Tumor dimensions of injected (Cohorts #1)
timeFrame: Up to 1 year after the last intra-tumoral dose
measure: Tumor dimensions of non-injected lesions (Cohort #2)
timeFrame: Up to 1 year after the last intra-tumoral dose
measure: Time to disease progression (local or distant)
timeFrame: From the start of treatment until the documentation of local or distant disease progression, assessed up to 1 year
measure: Biomarker analysis
timeFrame: Up to 1 year after the last intra-tumoral dose
measure: Granzyme B H-score
timeFrame: Up to 1 year after the last intra-tumoral dose
measure: NanoString Pan Cancer Immune Profiling Panel
timeFrame: Up to 1 year after the last intra-tumoral dose
measure: Tumor-infiltrating lymphocytes analysis
timeFrame: Up to 1 year after the last intra-tumoral dose
measure: Degree of tumor regression (percent)
timeFrame: Up to 1 year after the last intra-tumoral dose
measure: Changes in micro ribonucleic acid (RNA) expression
timeFrame: Baseline up to 1 year after the last intra-tumoral dose
measure: T-cell subset evaluation and changes in circulating microRNA
timeFrame: Up to 1 year after the last intra-tumoral dose
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Carlo M Contreras, MD
role: PRINCIPAL_INVESTIGATOR
References: