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

NCT04697576 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-20221NCI-2020-13282
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (10)

• Tumor dimensions of injected (Cohorts #1)

  Up to 1 year after the last intra-tumoral dose

• Tumor dimensions of non-injected lesions (Cohort #2)

  Up to 1 year after the last intra-tumoral dose

• 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

• Biomarker analysis

  Up to 1 year after the last intra-tumoral dose

• Granzyme B H-score

  Up to 1 year after the last intra-tumoral dose

Study Arms (2)

Cohort I (resectable Stage I-III melanoma)

EXPERIMENTAL

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.

Biological: Quadrivalent Inactivated Influenza Vaccine; Procedure: Resection

Cohort II (unresectable Stage IV)

EXPERIMENTAL

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.

Biological: Ipilimumab; Biological: Nivolumab; Biological: Pembrolizumab; Biological: Quadrivalent Inactivated Influenza Vaccine; Biological: Nivolumab + Relatlimab

Interventions

Ipilimumab BIOLOGICAL

immune checkpoint inhibitor

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Cohort II (unresectable Stage IV)

Nivolumab BIOLOGICAL

immune checkpoint inhibitor

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Cohort II (unresectable Stage IV)

Pembrolizumab BIOLOGICAL

immune checkpoint inhibitor

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Cohort II (unresectable Stage IV)

Quadrivalent Inactivated Influenza Vaccine BIOLOGICAL

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).

Also known as: Fluzone Quadrivalent, Fluzone Quadrivalent Influenza Vaccine, QIV, Quadrivalent Influenza Vaccine

Cohort I (resectable Stage I-III melanoma); Cohort II (unresectable Stage IV)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Cohort I (resectable Stage I-III melanoma)

Nivolumab + Relatlimab BIOLOGICAL

immune checkpoint inhibitor

Also known as: Opdualag

Cohort II (unresectable Stage IV)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females
• 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
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^3/mm\^3 (drawn at or not more than 30 days prior to the screening visit)
• Hemoglobin (Hgb) \>= 9 g/dL (drawn at or not more than 30 days prior to the screening visit)
• Platelet count \>= 100 x 10\^3/mm\^3 (drawn at or not more than 30 days prior to the screening visit)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN) or =\< 5 x ULN in patients with liver metastases (Cohort 2 only) (drawn at or not more than 30 days prior to the screening visit)
• Prothrombin time =\< 1.5 x ULN (drawn at or not more than 30 days prior to the screening visit)
• Total bilirubin =\< 1.5 x ULN (unconjugated bilirubin of \< 3 x ULN for patients with known Gilbert syndrome) (drawn at or not more than 30 days prior to the screening visit)
• Creatinine clearance of \>= 50 ml/min by Cockcroft-Gault equation (drawn at or not more than 30 days prior to the screening visit)
• Women of childbearing potential (WOCBP) must agree to use effective contraceptive methods from screening until at least:
• Cohort 1: 14 days after the surgical resection for subjects in Cohort 1
• Cohort 2:

You may not qualify if:

• 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
• Patients known to be HIV positive are eligible if they meet the following criteria within 30 days prior to randomization: stable and adequate CD4 counts (≥ 350 mm\^3), and serum HIV viral load of \< 25,000 IU/ml. Patients may be on or off anti-viral therapy so long as they meet the CD4 count criteria
• Pregnant or lactating patients
• Patients incapable of independently providing consent

Sponsors & Collaborators

• Carlo Contreras: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab; pembrolizumab; Influenza Vaccines; relatlimab; Opdualag

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Carlo M Contreras, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 5, 2021
• First Posted: January 6, 2021
• Study Start: October 20, 2021
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)