Recruiting

Phase 1

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

Sponsor:

Carlo Contreras

Code:

NCT04697576

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

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Ipilimumab

Nivolumab

Pembrolizumab

Quadrivalent Inactivated Influenza Vaccine

Resection

Study Details

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

Study ID

NCT04697576

Start date

Oct 20, 2021

Status verified date

Jul, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Sep 30, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Males or females
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
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) >= 8 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:

Nivolumab: 5 months after the last dose of either nivolumab or intralesional Flucelvax, whichever is later
Pembrolizumab: 4 months after the last dose of either pembrolizumab or intralesional Flucelvax, whichever is later
Ipilimumab: 3 months after the last dose of either ipilimumab or intralesional Flucelvax, whichever is later
Relatlimab + nivolumab (marketed under the trade name Opdualag): 5 months after the last dose of either Opdualag or intralesional Flucelvax, whichever is later.
Combination ipilimumab with other checkpoint inhibitor: Whichever is later:

3 months after the last dose of either ipilimumab or intralesional Flucelvax
Above-bulleted recommendation for nivolumab or pembrolizumab
Non-childbearing potential is defined as a woman who meets either of the following criteria: a) postmenopausal state defined as no menses for 12 months without an alternative medical cause, or b) documented hysterectomy, bilateral tubal ligation, or bilateral oophorectomy
Effective contraception methods are defined as one of the following:

True abstinence, defined as refraining from heterosexual intercourse, when this is in line with the preferred and usual lifestyle of the subject
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception
Condoms and spermicide
Diaphragm and spermicide
Oral or implanted hormonal contraceptive
An intra-uterine device
WOCBP must have a negative pregnancy test (serum or urine)

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
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

Study Design

Enrollment

36 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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.

Interventions

Ipilimumab

immune checkpoint inhibitor

Nivolumab

immune checkpoint inhibitor

Pembrolizumab

immune checkpoint inhibitor

Quadrivalent Inactivated Influenza Vaccine

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).

Resection

Undergo surgical resection

Nivolumab + Relatlimab

immune checkpoint inhibitor

Primary outcome measure

Incidence of adverse events (AEs) [ Time Frame: 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 ]

Central Contacts and Locations

Central contacts

The Ohio State University Comprehensive Cancer Center

800-293-5066 OSUCCCClinicaltrials@osumc.edu

Locations

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Carlo M. Contreras, MD

614-366-3681 Carlo.Contreras@osumc.edu

Principal Investigator:

Carlo M. Contreras, MD

More Information

Sponsor

Carlo Contreras

Last update posted

Jul 13, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Carlo Contreras on 2026-07-13.