Clinical Stage I Cutaneous Melanoma AJCC v8Phase 1NCT04697576
Intralesional Influenza Vaccine for the Treatment of Stage I-IV Melanoma
A Phase 1 study testing Ipilimumab, Nivolumab and Pembrolizumab in people with Clinical Stage I Cutaneous Melanoma AJCC v8 and Clinical Stage IA Cutaneous Melanoma AJCC v8, run by Carlo Contreras at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Clinical Stage I Cutaneous Melanoma AJCC v8, Clinical Stage IA Cutaneous Melanoma AJCC v8, Clinical Stage IB Cutaneous Melanoma AJCC v8
- What is being tested?
- Ipilimumab, Nivolumab and Pembrolizumab
- Type of treatment
- Vaccines, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Oct 2021to 31 Dec 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
The Ohio State University Comprehensive Cancer Center contact
United States1 site, 1 recruiting
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Carlo M. Contreras, MD, 614-366-3681, Carlo.Contreras@osumc.edu
Carlo M. Contreras, MD
About this study
Official title: Intralesional Influenza Vaccine for Patients With Melanoma
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
- 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
- Being tested
- Ipilimumab, Nivolumab, Pembrolizumab, Quadrivalent Inactivated Influenza Vaccine, Resection
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabBiological
Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4
immune checkpoint inhibitor
NivolumabBiological
Also called BMS-936558, MDX-1106, NIVO, ONO-4538
immune checkpoint inhibitor
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
immune checkpoint inhibitor
Quadrivalent Inactivated Influenza VaccineBiological
Also called Fluzone Quadrivalent, Fluzone Quadrivalent Influenza Vaccine, QIV, Quadrivalent 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).
ResectionProcedure or surgery
Also called Surgical Resection
Undergo surgical resection
Nivolumab + RelatlimabBiological
Also called Opdualag
immune checkpoint inhibitor
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Ipilimumab; Biological: Nivolumab; Biological: Pembrolizumab; Biological: Quadrivalent Inactivated Influenza Vaccine; Biological: Nivolumab + Relatlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 98 days
Secondary outcomes (10)
Tumor dimensions of injected (Cohorts #1)
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).
Measured: Up to 1 year after the last intra-tumoral dose
Tumor dimensions of non-injected lesions (Cohort #2)
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).
Measured: Up to 1 year after the last intra-tumoral dose
Time to disease progression (local or distant)
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.
Measured: From the start of treatment until the documentation of local or distant disease progression, assessed up to 1 year
Biomarker analysis
Will analyze immunohistochemistry density, cells/mm^2 of CD4, CD8, PD-L1, PD1, CD56, CD20, CD45RO, FOXP3. Summary statistics will be used.
Measured: Up to 1 year after the last intra-tumoral dose
Granzyme B H-score
Summary statistics will be used.
Measured: Up to 1 year after the last intra-tumoral dose
NanoString Pan Cancer Immune Profiling Panel
Summary statistics will be used.
Measured: Up to 1 year after the last intra-tumoral dose
Tumor-infiltrating lymphocytes analysis
Will analyze tumor-infiltrating lymphocytes: not identified, present (non-brisk), present (brisk), cannot be determined. Summary statistics will be used.
Measured: Up to 1 year after the last intra-tumoral dose
Degree of tumor regression (percent)
Summary statistics will be used.
Measured: Up to 1 year after the last intra-tumoral dose
Changes in micro ribonucleic acid (RNA) expression
Summary statistics will be used.
Measured: Baseline up to 1 year after the last intra-tumoral dose
T-cell subset evaluation and changes in circulating microRNA
Summary statistics will be used.
Measured: Up to 1 year after the last intra-tumoral dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2021
- Study start20 Oct 2021
- Primary completion30 Sep 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clinical Stage I Cutaneous Melanoma AJCC v8Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Carlo Contreras
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Carlo Contreras, Ohio State University Comprehensive Cancer Center
- Investigators
- Carlo M Contreras, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04697576
- Sponsor's protocol ID
- OSU-20221
- Other IDs
- NCI-2020-13282
- Status last verified
- Jul 2026
- First submitted
- 5 Jan 2021
- Last updated
- 13 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No