HPV Vaccine + Imiquimod + Metformin for Cervical Cancer

(HPV-VIM Trial)

Recruiting at 1 trial location

Overseen By Keneshia K Lane, B.A.

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Baylor College of Medicine

Must be taking: HPV vaccines, Metformin

Must not be taking: Investigational agents

Disqualifiers: Untreated brain metastases, Allergic reactions, Uncontrolled illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

85 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to explore whether additional treatments can help strengthen the participant's immune system to fight cancer caused by the Human Papillomavirus (HPV), a virus spread through intimate skin-to-skin contact. The trial will also monitor the safety of these treatments. The main questions it aims to answer are: Does the combination of treatments help the participant's body fight the cancer more effectively when used alongside standard therapy? What side effects or medical issues arise when using these experimental treatments? Researchers will use three experimental therapies along with the participant's standard treatment to find out if these therapies work better together than standard treatment alone. Participants will: Receive HPV vaccinations during the 2nd and 4th week of radiation, and again at weeks 8, 10, 12, and 16 after completing radiation. Have blood samples taken, tumor cells brushed from the surface, and imiquimod cream applied during each visit. Take a daily metformin pill and apply an imiquimod suppository three times a week for two weeks after each visit.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on corticosteroids, you can continue as long as your dose is stable for at least 4 weeks before starting the trial.

What data supports the effectiveness of the HPV Vaccine + Imiquimod + Metformin drug for cervical cancer?

The HPV 9-valent vaccine, part of the treatment, has been shown to significantly reduce the risk of high-grade cervical, vulvar, or vaginal diseases by 96.7% in females aged 16-26 years. This suggests its potential effectiveness in preventing cervical cancer. ^{1 2 3 4 5}

Is the HPV vaccine safe for humans?

The HPV vaccine, including Gardasil 9, has been shown to have a favorable safety profile with a low rate of serious adverse events. In a study from Italy, only 2 out of 5 serious adverse events were consistently associated with the vaccine, with a very low reporting rate of 0.750 per 100,000 doses. ^{5 6 7 8 9}

How does the HPV Vaccine + Imiquimod + Metformin treatment for cervical cancer differ from other treatments?

This treatment is unique because it combines the HPV vaccine, which helps prevent HPV infections that can lead to cervical cancer, with Imiquimod, a cream that boosts the immune system, and Metformin, a diabetes medication that may have anti-cancer effects. This combination aims to enhance the body's immune response and potentially improve treatment outcomes compared to using these components separately. ^{1 2 4 6 10}

Research Team

Jan Sunde, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for individuals with cancers caused by HPV, such as cervical, vulvar, and vaginal cancer. Participants will use the treatments alongside their standard therapy. They must be able to attend regular visits for vaccinations, sample collections, cream application, and follow a regimen of daily pills and thrice-weekly suppositories.

Inclusion Criteria

I agree not to donate blood during the study or for 90 days after the last treatment.

My hepatitis B virus load is undetectable with treatment.

I had hepatitis C but am cured, or I'm being treated with no detectable virus.

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study.

I do not have any uncontrolled illnesses.

Patients with psychiatric illness/social situations that would limit compliance with study requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive intratumoral HPV vaccinations during the 2nd and 4th week of radiation

4 weeks

2 visits (in-person)

Post-Radiation Treatment

Participants receive HPV vaccinations at weeks 8, 10, 12, and 16 after completing radiation, along with daily metformin and imiquimod suppository

8 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• HPV Vaccine
• Imiquimod
• Metformin

Trial Overview The study tests if combining an HPV vaccine with imiquimod (a cream that stimulates immune response) and metformin (a diabetes drug thought to fight cancer) improves the body's ability to combat HPV-related cancers when used with standard treatments.

Participant Groups

Group I: Treatment group Experimental Treatment 1 Intervention

The treatment group will be compared to a historical control. The investigator will evaluate the immune changes within the tumor microenvironment and validate why the combination immunotherapy study elicited such a robust immune response which led to complete resolution of the cancer, in comparison to the standard of care, chemoradiation. In this study, participants will undergo a series of treatment visits during and after radiation therapy to assess the effectiveness of the experimental combination therapy.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Harris Health

Collaborator

Trials

3

Recruited

1,500+

Baylor St. Luke's Medical Center

Collaborator

Trials

4

Recruited

500+

Dan L Duncan Comprehensive Cancer Center

Collaborator

Trials

1

Recruited

90+

Findings from Research

In a study involving 741 healthy girls aged 9-15, co-administration of the HPV-16/18 vaccine with the hepatitis B vaccine met non-inferiority criteria for immune responses, showing that both vaccines can be effectively given together without compromising their efficacy.

The co-administered vaccines were well tolerated, with high seroprotection rates achieved for both hepatitis B (97.9% to 100%) and HPV (≥99%), indicating that this combination is safe and effective for adolescent girls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls. Schmeink, CE., Bekkers, RL., Josefsson, A., et al.[2022]

In a study involving 6,967 women over a median follow-up of 4.2 years, the HPV16/18 vaccine Cervarix showed high efficacy in preventing persistent HPV16 or HPV18 infections, with 80.9% efficacy for three doses, 84.1% for two doses, and even 100% for one dose.

This suggests that fewer than three doses of the HPV vaccine may provide similar protection against HPV infections, indicating a potential for simplifying vaccination regimens, especially in areas where access to healthcare is limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine. Kreimer, AR., Rodriguez, AC., Hildesheim, A., et al.[2022]

The study found that certain serious autoimmune adverse events (SAAEs) such as gastroenteritis, arthritis, and systemic lupus erythematosus were significantly more likely to occur in individuals who received the GARDASIL HPV vaccine compared to controls, with symptoms typically appearing 6 to 55 days post-vaccination.

However, conditions like Guillain-Barre syndrome and thrombocytopenia showed no increased risk associated with the HPV4 vaccine, suggesting that while some autoimmune events may be linked to the vaccine, others are not affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case-control study of quadrivalent human papillomavirus vaccine-associated autoimmune adverse events. Geier, DA., Geier, MR.[2022]

The 9-valent HPV vaccine (9vHPV) is as effective as the quadrivalent HPV vaccine (qHPV) in generating immune responses against HPV types 6, 11, 16, and 18, while also providing a 96.7% risk reduction against high-grade cervical, vulvar, or vaginal diseases related to five additional HPV types in females aged 16-26.

The 9vHPV vaccine has been shown to be safe and well tolerated, with evidence supporting its efficacy in both males and females aged 9-26, indicating its potential to significantly expand protection against HPV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence. Signorelli, C., Odone, A., Ciorba, V., et al.[2022]

Gardasil is the first vaccine approved by the FDA specifically to prevent cervical cancer, precancerous lesions, and genital warts caused by certain types of human papillomavirus (HPV).

The vaccine is recommended for females aged 9 to 26 years and received expedited approval in just six months due to its potential to significantly improve health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New vaccine prevents cervical cancer. [2015]

A study involving 215,965 individuals who received the nine-valent HPV vaccine (HPV9) found no new safety concerns, confirming its established safety profile from previous research.

While some elevated event categories were noted, such as skin disorders and ill-defined conditions, most were either previously known or had other causes, and no deaths were linked to the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use. Hansen, J., Yee, A., Lewis, N., et al.[2023]

A comprehensive analysis of adverse events (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS) identified 3,112 AEs for Cervarix, 31,606 for Gardasil, and 6,872 for Gardasil 9, highlighting the need for ongoing monitoring of vaccine safety.

The study found 46 unique serious adverse events (SAEs) associated with the HPV vaccines, clustered around behavioral, neurological, immune, nervous, and reproductive systems, indicating that while the vaccines are effective, further research is needed to understand the cause-and-effect relationships of these AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines. Zi, W., Yang, Q., Su, J., et al.[2022]

In a study of 266,647 doses of Gardasil-9® administered in Puglia, Italy, only 22 adverse events following immunization (AEFIs) were reported, resulting in a low reporting rate of 8.25 per 100,000 doses, indicating a favorable safety profile for the vaccine.

Out of the 22 reported AEFIs, only 5 were classified as serious, with 2 leading to hospitalization; however, only 2 serious AEFIs were consistently associated with the vaccine, suggesting that the benefits of Gardasil-9® outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Safety Profile of the 9-Valent HPV Vaccine Based on Data from the Puglia Region of Southern Italy. Di Lorenzo, A., Berardi, P., Martinelli, A., et al.[2022]

Over 4 years of post-licensure safety surveillance of the HPV-16/18 vaccine (Cervarix) showed that the most commonly reported adverse events were consistent with those expected in the general population, indicating a favorable safety profile.

No significant patterns of serious immune-mediated diseases were found, and the incidences of conditions like Bell's palsy and Guillain-Barré syndrome were within expected ranges, reinforcing the vaccine's acceptable benefit-risk profile for adolescent girls and women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience. Angelo, MG., Zima, J., Tavares Da Silva, F., et al.[2021]

The nine-valent HPV vaccine, Gardasil9, significantly increases the efficacy against cervical cancer from 70% to 90% compared to the quadrivalent vaccine, covering a broader range of HPV types.

Gardasil9 also provides high efficacy (97%) against lesions associated with HPV types 31, 33, 45, 52, and 58, while maintaining similar effectiveness against HPV types 6, 11, 16, and 18 as the quadrivalent vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nine-valent HPV vaccine - new generation of HPV vaccine]. Fait, T., Dvořák, V., Pilka, R.[2018]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls. [2022]

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

Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

A case-control study of quadrivalent human papillomavirus vaccine-associated autoimmune adverse events. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence. [2022]

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

New vaccine prevents cervical cancer. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use. [2023]

7. England pubmed.ncbi.nlm.nih.gov

OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Real-Life Safety Profile of the 9-Valent HPV Vaccine Based on Data from the Puglia Region of Southern Italy. [2022]

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

Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience. [2021]

10. Czech Republic pubmed.ncbi.nlm.nih.gov

[Nine-valent HPV vaccine - new generation of HPV vaccine]. [2018]