Flu Vaccine for Melanoma

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Carlo Contreras

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, Brain metastasis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 14 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the flu vaccine might help treat melanoma, a type of skin cancer. Researchers are testing whether injecting the flu vaccine directly into the melanoma tumor can shrink the tumor or reduce the cancer's spread. The study involves two groups: one with melanoma that can be surgically removed (Stages I-III) and another with advanced melanoma that cannot be removed (Stage IV). Individuals with a confirmed melanoma diagnosis and a noticeable tumor suitable for injection might be a good fit for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on certain immunosuppressive medications or corticosteroids above a specific dose within 14 days of the study.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the quadrivalent inactivated flu vaccine is generally safe for cancer patients. Studies have found a very low risk of Guillain-Barré Syndrome (GBS) after receiving this vaccine, with only 1 to 2 extra cases per million doses. For patients receiving immune checkpoint inhibitors, the vaccine does not appear to increase the risk of immune-related side effects.

This vaccine is already approved for use in the general population to prevent the flu, indicating it is generally well-tolerated. However, administering the vaccine directly into a melanoma tumor (intralesional) is a new method being tested in this trial, so more specific safety information for this approach is still being collected. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for melanoma?

Researchers are excited about this treatment for melanoma because it uniquely uses the quadrivalent inactivated influenza vaccine, typically used for flu prevention, to target cancer cells. Unlike standard treatments like ipilimumab, nivolumab, relatlimab, or pembrolizumab, which are immune checkpoint inhibitors, this approach directly introduces the flu vaccine into the tumor, potentially stimulating an immune response against the cancer. This novel delivery method could enhance the immune system's ability to recognize and attack melanoma cells, offering a fresh angle on treatment that could complement existing therapies.

What evidence suggests that the flu vaccine might be an effective treatment for melanoma?

Research has shown that the quadrivalent inactivated flu vaccine is safe and can reduce death and flu-related complications in cancer patients. While typically used to prevent the flu, researchers are now testing it directly on melanoma tumors in this trial. Participants in Cohort I, with resectable Stage I-III melanoma, will receive the vaccine both intramuscularly and intratumorally before surgery. Participants in Cohort II, with unresectable Stage IV melanoma, will receive the vaccine in the same manner alongside standard care treatments. Early results suggest that vaccines, including this one for melanoma, are generally safe and have fewer side effects than other cancer treatments. Although this is a new approach, the vaccine might help the body's immune system attack melanoma cells. ^{1 2 6 7 8}

Who Is on the Research Team?

Carlo M. Contreras, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-99 with stage I-IV cutaneous melanoma. Participants must have at least one palpable tumor deposit suitable for injection and be in good physical condition (ECOG PS 0-1). Exclusions include allergies to flu vaccines, recent immunosuppressants use, autoimmune diseases, ocular/mucosal melanoma, brain metastasis, recent melanoma therapy except surgery, incarceration, HIV positivity or pregnancy.

Inclusion Criteria

I am fully active or can carry out light work.

I have a melanoma tumor that can be felt and measured to be at least 1 cm.

My skin cancer is confirmed as melanoma and is in an early or advanced stage.

Exclusion Criteria

I have an autoimmune disease.

You have had a biopsy to diagnose melanoma in your eye or on a mucous membrane.

I am unable to give consent on my own.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive quadrivalent inactivated influenza vaccine intramuscularly on day 0 and intratumorally on specified days, with surgery on day 28 for Cohort I and additional intratumoral doses for Cohort II

14 weeks

Multiple visits for intratumoral injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Quadrivalent Inactivated Influenza Vaccine

Trial Overview The study tests if injecting the influenza vaccine directly into a melanoma tumor can reduce its size or spread. It's a phase I trial that also involves standard therapies like Ipilimumab and Nivolumab. Patients are grouped based on their cancer stage and receive either intralesional vaccine plus other treatments or those treatments alone.

How Is the Trial Designed?

Group I: Cohort II (unresectable Stage IV) Experimental Treatment 5 Interventions

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.

Group II: Cohort I (resectable Stage I-III melanoma) Experimental Treatment 2 Interventions

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.

Quadrivalent Inactivated Influenza Vaccine is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Quadrivalent Inactivated Influenza Vaccine for:

• Influenza prophylaxis

Approved in European Union as Quadrivalent Inactivated Influenza Vaccine for:

• Influenza prophylaxis

Approved in Canada as Quadrivalent Inactivated Influenza Vaccine for:

• Influenza prophylaxis

Approved in Japan as Quadrivalent Inactivated Influenza Vaccine for:

• Influenza prophylaxis

Approved in China as Quadrivalent Inactivated Influenza Vaccine for:

• Influenza prophylaxis

Approved in Switzerland as Quadrivalent Inactivated Influenza Vaccine for:

• Influenza prophylaxis

Who Is Running the Clinical Trial?

Carlo Contreras

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

This clinical trial is investigating two innovative immunotherapy approaches for melanoma in 40 patients with advanced stages (IIb-IV), focusing on enhancing the immune response through novel constructs like Influenza virosomes and a recombinant Vaccinia virus.

The study will monitor safety and adverse events while assessing immunological efficacy and disease-free survival over a 2-year follow-up, aiming to refine treatment options beyond surgery for melanoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterologous prime-boost immunotherapy of melanoma patients with Influenza virosomes, and recombinant Vaccinia virus encoding 5 melanoma epitopes and 3 co-stimulatory molecules. A multi-centre phase I/II open labeled clinical trial. Adamina, M., Weber, WP., Rosenthal, R., et al.[2008]

In a study involving 41 patients with advanced melanoma, a prime-boost vaccine strategy using DNA and modified vaccinia virus induced strong immune responses in 71% of patients at high doses, suggesting its efficacy in activating T cells against melanoma antigens.

The treatment was well tolerated, with only mild side effects like flu-like symptoms, and patients showing immune responses had significantly longer survival and time-to-progression, indicating a promising link between immune activation and clinical benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and immunological responses in metastatic melanoma patients vaccinated with a high-dose poly-epitope vaccine. Dangoor, A., Lorigan, P., Keilholz, U., et al.[2020]

Current FDA-approved treatment for advanced melanoma is limited to IFN-alpha2b, highlighting the need for new therapies as no satisfactory options exist once melanoma spreads.

Recent randomized trials of polyvalent melanoma vaccines show promise in delaying tumor progression, particularly in patients with specific human leukocyte antigen phenotypes, suggesting that a diverse range of antigens may enhance immune response against melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging melanoma vaccines. Bystryn, JC., Rudolph, JL.[2007]

The polyvalent melanoma tumor antigen vaccine, tested in a Phase I study with 13 patients, was found to be safe, with only mild side effects like transient urticaria at the injection site.

The vaccine successfully induced immune responses in some patients, with one patient achieving complete regression of cutaneous metastases and remaining disease-free for 2 years, while another had stable disease for 14 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation and characterization of a polyvalent human melanoma antigen vaccine. Bystryn, JC., Jacobsen, S., Harris, M., et al.[2007]

Despite significant advancements in understanding melanoma antigens and immune responses through decades of research, achieving lasting clinical benefits from melanoma vaccines remains rare.

Recent clinical trials involving CTLA-4 inhibitors and BRAF inhibitors show promise, suggesting that combining these therapies with active immunotherapy could enhance long-term control of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melanoma vaccines: developments over the past 10 years. Klein, O., Schmidt, C., Knights, A., et al.[2012]

Canvaxin, a therapeutic polyvalent cancer vaccine, significantly improves overall survival rates in patients with metastatic melanoma, with five-year survival rates of 39% for stage IV and 49% for stage III patients compared to much lower rates in non-vaccine patients.

The effectiveness of Canvaxin is closely linked to the patient's immune response, particularly the levels of specific antibodies and delayed-type hypersensitivity reactions, which correlate with improved survival outcomes after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune response to postsurgical adjuvant active immunotherapy with Canvaxin polyvalent cancer vaccine: correlations with clinical course of patients with metastatic melanoma. Morton, DL.[2007]

Biotherapy, including whole cell melanoma vaccines, is emerging as a significant treatment option for malignant diseases, complementing traditional methods like surgery and chemotherapy.

Polyvalent whole cell vaccines are preferred over single antigen vaccines because they target multiple tumor antigens, which helps overcome tumor resistance and enhances the immune response against cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer vaccines with emphasis on a viral oncolysate melanoma vaccine. Horvath, JC., Horak, A., Sinkovics, JG., et al.[2020]

The dendritoma vaccine demonstrated a low toxicity profile, with all reported side effects being less than grade 3, making it a safer option for patients with stage IV melanoma.

Patients receiving three or more doses of the dendritoma vaccine had a significantly improved median overall survival of 43.1 months compared to 16.7 months for those receiving fewer doses, highlighting the importance of dosing frequency in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/IIa clinical trial in stage IV melanoma of an autologous tumor-dendritic cell fusion (dendritoma) vaccine with low dose interleukin-2. Greene, JM., Schneble, EJ., Jackson, DO., et al.[2021]

Vaccines for melanoma are considered safe and have lower toxicity compared to current treatments, making them a promising option for patients.

Clinical trials indicate that these vaccines can effectively stimulate immune responses, leading to improved outcomes such as longer recurrence-free survival in patients compared to control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melanoma vaccines: what we know so far. Bystryn, JC., Reynolds, SR.[2015]

In a study of 27 patients with advanced colon cancer, the CancerVax vaccine significantly increased immune responses, specifically anti-TA90 IgG and IgM titers, which correlated with improved overall survival rates, particularly in patients with higher IgM levels.

The median overall survival for patients receiving CancerVax was 21.9 months, and peak IgMTA90 titer was identified as a significant predictor of survival, suggesting that the vaccine may enhance patient outcomes in advanced colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CancerVax, an allogeneic tumor cell vaccine, induces specific humoral and cellular immune responses in advanced colon cancer. Habal, N., Gupta, RK., Bilchik, AJ., et al.[2020]

Citations

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Safety of Inactivated Influenza Vaccine in Cancer Patients ... The risk of GBS after seasonal influenza vaccine is extremely small, estimated to be between 1 and 2 additional cases per million doses [13]. The notion that ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9412390/

Safety and Efficacy of Influenza Vaccination in Patients ... Vaccination against influenza is safe, reduces mortality and improves infection-related outcomes among adults with cancer [11,12]. Consequently, annual ...

3. academic.oup.com academic.oup.com/ofid/article/11/10/ofae559/7775992

Relative Effectiveness and Immunogenicity of Quadrivalent ... Immunogenicity studies suggest that recombinant influenza vaccine (RIV) may provide better protection against influenza than standard-dose inactivated influenza ...

4. withpower.com withpower.com/trial/phase-1-melanoma-10-2021-7d988?condition=Cutaneous+Melanoma&overallStatus=Recruiting&hasNoPlacebo=false

Flu Vaccine for Melanoma Clinical trials have shown that vaccines, including those for melanoma, are generally safe to use and have much less toxicity than current therapies for ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05540522

NCT05540522 | A Study to Evaluate a Modified RNA ... This is a Phase 3, randomized, observer-blinded study to evaluate the efficacy, safety, tolerability, and immunogenicity of a quadrivalent influenza modRNA ...

6. withpower.com withpower.com/trial/phase-4-melanoma-9-2017-5a7a3

Flu Vaccine for Melanoma Patients · Info for Participants There is a positive correlation between the ability of these vaccines to stimulate immune responses against melanoma and improved clinical outcomes, leading to ...

7. cdc.gov cdc.gov/mmwr/volumes/73/rr/rr7305a1.htm

Prevention and Control of Seasonal Influenza with Vaccines Clinical Trial to compare safety of recombinant influenza vaccine (RIV4) versus quadrivalent inactivated influenza vaccine (IIV4) in pregnancy.

8. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04697576/intralesional-influenza-vaccine-for-the-treatment-of-stage-i-iv-melanoma

Intralesional Influenza Vaccine for the Treatment of Stage I ... This phase I trial investigates the effects of influenza vaccine in treating patients with stage I-IV melanoma.