Flu Vaccine for Breast Cancer

Overseen By Angela Limburg, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Rush University Medical Center

Must not be taking: Anticoagulants, Corticosteroids, Immunosuppressants

Disqualifiers: Uncontrolled illness, Egg allergy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial excludes patients who are currently on anticoagulant therapy, corticosteroids, or immunosuppressive agents, so you would need to stop these medications to participate.

What data supports the effectiveness of the flu vaccine as a treatment for breast cancer?

The research does not provide direct evidence supporting the effectiveness of the flu vaccine for breast cancer. However, studies on other cancer vaccines, like those targeting HER2 or survivin proteins, show that vaccines can stimulate immune responses and potentially reduce cancer recurrence or slow tumor growth. ^{1 2 3 4 5}

Is the flu vaccine generally safe for humans?

The flu vaccine, including versions like Fluzone Quadrivalent, has been studied for safety and is generally considered safe for humans. Some studies have noted that certain versions of the vaccine may cause more local reactions (like soreness at the injection site) and mild systemic reactions (like fever or fatigue) compared to non-adjuvanted vaccines, but these are typically not serious. ^{6 7 8 9 10}

How is the Fluzone Quadrivalent vaccine unique in treating breast cancer?

The Fluzone Quadrivalent vaccine is unique because it is traditionally used as a flu vaccine, and its use in breast cancer is novel, potentially leveraging its immune-stimulating properties to help the body fight cancer, unlike standard breast cancer treatments that directly target cancer cells. ^{1 2 5 11 12}

What is the purpose of this trial?

This Phase 1 study will assess the safety and efficacy (usefulness) of administering 2 doses of seasonal flu vaccine directly into breast cancer tissue (primary tumor), and will study the tumor and whole body response to the vaccine. If the tumor is palpable (able to fee by touch), the vaccine will be administered by a Surgeon/oncologist in the outpatient floor - both experienced and trained. If not palpable, the procedure will be done via guided Ultrasound by our Breast Radiologist -- both experienced and trained. Women with triple-negative (TNBC) and HER2+ types of breast cancer will be eligible for enrollment. Up to 18 subjects may be enrolled at Rush. Successive groups of 3 subjects per breast cancer type will be given increasing doses of vaccine. There are 3 potential dosing groups (half-dose, full dose, and high dose). Blood, stool (optional), and tumor tissue samples will be collected and tested. The active participation period is from one week prior to starting chemotherapy through three months post surgery.

Research Team

Ruta Rao

Principal Investigator

Rush University Medical Center

Eligibility Criteria

This trial is for women with triple-negative or HER2+ breast cancer who are about to start standard chemotherapy. They should be relatively active and able (ECOG 0-2) and have a confirmed diagnosis through tissue samples. The study excludes certain individuals, but the criteria aren't fully listed here.

Inclusion Criteria

My breast cancer is confirmed as either triple-negative or HER2 positive.

I am able to care for myself and perform daily activities.

I am set to receive recommended initial chemotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 doses of seasonal flu vaccine directly into breast cancer tissue, with increasing doses across groups

3 months

Multiple visits for vaccine administration and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of dose-limiting toxicity

3 months post surgery

Treatment Details

Interventions

• Fluzone Quadrivalent

Trial Overview The study tests injecting flu vaccine directly into breast cancer tumors before chemo starts. Participants will receive different doses of the vaccine in palpable or non-palpable tumors, administered by trained professionals using touch or ultrasound guidance.

Participant Groups

Group I: Intratumoral influenza vaccine Experimental Treatment 1 Intervention

Fluzone Quadrivalent is already approved in United States, European Union for the following indications:

Approved in United States as Fluzone Quadrivalent for:

• Prevention of disease caused by influenza A subtype viruses and type B virus contained in the vaccine

Approved in European Union as Fluzone Quadrivalent for:

• Prevention of disease caused by influenza A subtype viruses and type B virus contained in the vaccine

Who Is Running the Clinical Trial?

Rush University Medical Center

Lead Sponsor

Trials

448

Recruited

247,000+

Findings from Research

E75, an immunogenic peptide from the HER2 protein, has been shown to be safe and effective in stimulating an immune response in breast cancer patients when used as a vaccine with an immunoadjuvant.

In a study of 187 patients, those vaccinated with E75 + GM-CSF had a 5-year disease-free survival rate of 89.7%, significantly higher than the 80.2% in the control group, indicating a 48% reduction in the risk of cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Development of the E75 Vaccine in Breast Cancer. Clifton, GT., Gall, V., Peoples, GE., et al.[2020]

The phase I clinical trial involving 10 patients with metastatic breast cancer demonstrated that the Her-2/neu multipeptide vaccine was safe and well-tolerated, with local erythema being the only reported side effect.

The vaccine successfully induced Her-2/neu-specific antibodies in 8 out of 10 patients, suggesting potential for clinical benefit similar to existing anti-Her-2 antibody therapies, while also reducing regulatory T cells that may suppress immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study. Wiedermann, U., Wiltschke, C., Jasinska, J., et al.[2019]

The study demonstrated that a survivin peptide microparticle vaccine significantly slowed tumor growth in a triple negative breast cancer model using 4T1 tumor cells in mice, indicating its potential efficacy as an immunotherapy.

Vaccination led to a specific immune response, as evidenced by increased gamma interferon production in splenocytes, suggesting that targeting survivin could be a promising approach for treating triple negative breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survivin (BIRC5) Peptide Vaccine in the 4T1 Murine Mammary Tumor Model: A Potential Neoadjuvant T Cell Immunotherapy for Triple Negative Breast Cancer: A Preliminary Study. Burkholz, SR., Herst, CV., Carback, RT., et al.[2023]

In the GIADA trial involving 43 premenopausal patients with Luminal B-like breast cancer, a pathologic complete response (pCR) was achieved in 16.3% of patients, with a notably higher response rate of 50% in those with PAM50 Basal subtype tumors.

The study found that tumor-infiltrating lymphocytes (TILs) and immune-related gene expression were significantly associated with pCR, suggesting that a more immune-activated tumor microenvironment may enhance the effectiveness of immunotherapy in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Chemotherapy and Immunotherapy in Luminal B-like Breast Cancer: Results of the Phase II GIADA Trial. Dieci, MV., Guarneri, V., Tosi, A., et al.[2023]

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]

MF59® adjuvanted trivalent influenza vaccines were effective in preventing laboratory-confirmed influenza in older adults, showing a vaccine effectiveness of 45% compared to no vaccination, particularly effective against influenza A(H1N1) with a 61% effectiveness.

While these adjuvanted vaccines were more effective than no vaccination, they were associated with a higher incidence of local and systemic adverse events compared to traditional non-adjuvanted vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of the efficacy, effectiveness and safety of MF59® adjuvanted seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age. O Murchu, E., Comber, L., Jordan, K., et al.[2023]

In a phase II study involving 187 patients with advanced cancers, the oral administration of SF-SP showed promising efficacy, with one complete response in breast cancer and 29 partial responses across various cancer types, particularly colorectal, gastric, and breast cancers.

The treatment was well-tolerated, with no serious toxicity reported, indicating a favorable safety profile for SF-SP in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cooperative phase II study of spansule tegafur (SF-SP)]. Taguchi, T.[2013]

ICRF-187, administered at a dose of 3 g/M2/day for 3 days, was well tolerated in a phase II trial involving 56 children with solid tumors and acute leukemia, with the main side effect being hematopoietic depression.

Despite being well tolerated, ICRF-187 showed no objective responses in treating leukemia or solid tumors, suggesting that it may require a different administration schedule to be effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of ICRF-187 in children with solid tumors and acute leukemia. Vats, T., Kamen, B., Krischer, JP.[2019]

The MFL regimen (mitoxantrone, high-dose 5-FU, and leucovorin) showed limited efficacy in treating previously treated advanced breast cancer, with only a 7.6% overall objective response rate and a median survival of 16 months among 13 patients.

Significant toxicities were observed, including cardiotoxicity and leukopenia, highlighting the need for careful monitoring, especially in patients with prior chemotherapy or heart issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of previously treated metastatic breast cancer by mitoxantrone and 48-hour continuous infusion of high-dose 5-FU and leucovorin (MFL): low palliative benefit and high treatment-related toxicity. Yen, CC., Tung, SL., Hsieh, RK., et al.[2019]

The MLF regimen, which combines mitoxantrone, leucovorin, and continuous infusion of 5-fluorouracil, showed a 46% overall response rate in 27 patients with advanced breast cancer, with a 100% response rate in previously untreated patients.

The treatment demonstrated manageable toxicity, with only 26% of patients experiencing grade 3 nausea/vomiting and 4% experiencing grade 4 hematological toxicity, suggesting it is a viable option for patients, including those who have been heavily pretreated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitoxantrone, leucovorin and high-dose infusional 5-fluorouracil: an effective and well-tolerated regimen for the treatment of advanced breast cancer. Wils, JA.[2019]

Current breast cancer vaccines typically target only one part of the immune system, which may limit their effectiveness; a more comprehensive approach is needed.

Recent advances in developing a multivalent glycolipopeptide vaccine have shown promising results in stimulating multiple immune responses, potentially improving both treatment and prevention of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in multivalent self adjuvanting glycolipopeptide vaccine strategies against breast cancer. Chentoufi, AA., Nesburn, AB., BenMohamed, L.[2021]

The MFCH401-based tricomponent anti-HER2 cancer vaccine significantly enhances the immune response against HER2-overexpressing breast cancer cells, showing stronger humoral and cellular immunity compared to simpler two-component vaccines.

Incorporating the lipopeptide Pam3CSK4 into the vaccine formulation was found to provide superior immunostimulatory activity, improving the overall effectiveness of the vaccine in targeting breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and functional studies of self-adjuvanting multicomponent anti-HER2 cancer vaccines. Feng, Q., Yu, X., Wang, Y., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Development of the E75 Vaccine in Breast Cancer. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Survivin (BIRC5) Peptide Vaccine in the 4T1 Murine Mammary Tumor Model: A Potential Neoadjuvant T Cell Immunotherapy for Triple Negative Breast Cancer: A Preliminary Study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant Chemotherapy and Immunotherapy in Luminal B-like Breast Cancer: Results of the Phase II GIADA Trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Melanoma vaccines: what we know so far. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Systematic review of the efficacy, effectiveness and safety of MF59® adjuvanted seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

[Cooperative phase II study of spansule tegafur (SF-SP)]. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of ICRF-187 in children with solid tumors and acute leukemia. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Treatment of previously treated metastatic breast cancer by mitoxantrone and 48-hour continuous infusion of high-dose 5-FU and leucovorin (MFL): low palliative benefit and high treatment-related toxicity. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Mitoxantrone, leucovorin and high-dose infusional 5-fluorouracil: an effective and well-tolerated regimen for the treatment of advanced breast cancer. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Recent advances in multivalent self adjuvanting glycolipopeptide vaccine strategies against breast cancer. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Synthesis and functional studies of self-adjuvanting multicomponent anti-HER2 cancer vaccines. [2022]