HPV Vaccine + Imiquimod + Metformin for Cervical Cancer
(HPV-VIM Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
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.
12345Is 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.
56789How 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.
124610Eligibility 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.
+16 more
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.
+3 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment groupExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Baylor St. Luke's Medical Center- Dan L. Duncan Comprehensive Cancer CenterHouston, TX
Harris Health Smith ClinicHouston, TX
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Who Is Running the Clinical Trial?
Baylor College of MedicineLead Sponsor
Harris HealthCollaborator
Baylor St. Luke's Medical CenterCollaborator
Dan L Duncan Comprehensive Cancer CenterCollaborator
References
Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls. [2022]To evaluate co-administration of GlaxoSmithKline Biologicals' human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB).
Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine. [2022]Three-dose regimens for human papillomavirus (HPV) vaccines are expensive and difficult to complete, especially in settings where the need for cervical cancer prevention is greatest.
A case-control study of quadrivalent human papillomavirus vaccine-associated autoimmune adverse events. [2022]GARDASIL (Merck & Co., Inc., Whitehouse Station, NJ, USA) is a quadrivalent human papillomavirus (HPV4) vaccine. An epidemiological study was undertaken to evaluate concerns about the potential for HPV4 vaccination to induce serious autoimmune adverse events (SAAEs). The vaccine adverse event reporting system (VAERS) database was examined for adverse event reports associated with vaccines administered from January 2006 through December 2012 to recipients between 18 and 39 years old with a listed residence in the USA and a specified female gender. It was observed that cases with the SAAE outcomes of gastroenteritis (odds ratio (OR) = 4.6, 95% confidence interval (CI) = 1.3-18.5), arthritis (OR = 2.5, 95% CI = 1.4-4.3), systemic lupus erythematosus (OR = 5.3, 95% CI = 1.5-20.5), vasculitis (OR = 4, 95% CI = 1.01-16.4), alopecia (OR = 8.3, 95% CI = 4.5-15.9), or CNS conditions (OR = 1.8, 95% CI = 1.04-2.9) were significantly more likely than controls to have received HPV4 vaccine (median onset of SAAE symptoms from 6 to 55 days post-HPV4 vaccination). Cases with the outcomes of Guillain-Barre syndrome (OR = 0.75, 95% CI = 0.42-1.3) or thrombocytopenia (OR = 1.3, 95% CI = 0.48-3.5) were no more likely than controls to have received HPV4 vaccine. Cases with the general health outcomes of infection (OR = 0.72, 95% CI = 0.27-1.7), conjunctivitis (OR = 0.88, 95% CI = 0.29-2.7), or diarrhea (OR = 1.01, 95% CI = 0.83-1.22) were no more likely than controls to have received HPV4 vaccine. Previous case series of SAAEs and biological plausibility support the observed results. Additional studies should be conducted to further evaluate the potential biological mechanisms involved in HPV4 vaccine-associated SAAEs in animal model systems, and to examine the potential epidemiological relationship between HPV4 vaccine-associated SAAEs in other databases and populations.
Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence. [2022]In 2014, the Food and Drug Administration approved a new human papillomavirus 9-valent vaccine (9vHPV), targeting nine HPV types: HPV types 6, 11, 16, and 18, which are also targeted by the quadrivalent HPV vaccine (qHPV), plus five additional high cancer risk HPV types (HPV types 31, 33, 45, 52, and 58). The aim of the current study was to systematically retrieve, qualitatively and quantitatively pool, as well as critically appraise all available evidence on 9vHPV from randomized controlled trials (RCTs). We conducted a systematic review of the literature on 9vHPV efficacy, immunogenicity and safety, as well as a systematic search of registered, completed, and ongoing RCTs. We retrieved and screened 227 records for eligibility. A total of 10 publications reported on RCTs' results on 9vHPV and were included in the review. Sixteen RCTs on 9vHPV have been registered on RCT registries. There is evidence that 9vHPV generated a response to HPV types 6, 11, 16 and 18 that was non-inferior to qHPV. Vaccine efficacy against five additional HPV type-related diseases was directly assessed on females aged 16-26 years (risk reduction against high-grade cervical, vulvar or vaginal disease = 96·7%, 95% CI 80·9%-99·8%). Bridging efficacy was demonstrated for males and females aged 9-15 years and males aged 16-26 years (the lower bound of the 95% CIs of both the geometric mean titer ratio and difference in seroconversion rates meeting the criteria for non-inferiority for all HPV types). Overall, 9vHPV has been proved to be safe and well tolerated. Other RCTs addressed: 9vHPV co-administration with other vaccines, 9vHPV administration in subjects that previously received qHPV and 9vHPV efficacy in regimens containing fewer than three doses. The inclusion of additional HPV types in 9vHPV offers great potential to expand protection against HPV infection. However, the impact of 9vHPV on reducing the global burden of HPV-related disease will greatly depend on vaccine uptake, coverage, availability, and affordability.
New vaccine prevents cervical cancer. [2015]The Food and Drug Administration has approved Gardasil, the first vaccine developed to prevent cervical cancer and precancerous genital lesions and genital warts due to certain types of human papillomavirus (HPV). The vaccine is approved for use in females ages 9 years to 26 years. Gardasil was evaluated and approved in six months under the FDA's priority review process--a process for products with potential to provide significant health benefits.
Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use. [2023]The nine-valent human papillomavirus vaccine (HPV9, Gardasil®9) was licensed in the USA in December 2014. This study was a multiyear post-licensure study to assess HPV9 safety following routine administration.
OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines. [2022]Three licensed human papillomavirus (HPV) vaccines (Cervarix, Gardasil, and Gardasil 9) have been effectively used to prevent infection with oncogenic HPV types; however, many adverse events (AEs) have also been reported following their vaccinations. We assessed AE profiles after receiving the HPV vaccines based on the reported data from Vaccine Adverse Event Reporting System (VAERS).
Real-Life Safety Profile of the 9-Valent HPV Vaccine Based on Data from the Puglia Region of Southern Italy. [2022]Human Papillomavirus (HPV) is responsible for epithelial lesions and cancers in both males and females. The latest licensed HPV vaccine is Gardasil-9®, a 9-valent HPV vaccine which is effective not only against the high-risk HPV types, but also against the ones responsible for non-cancerous lesions. This report describes adverse events following Gardasil-9® administration reported in Puglia, southern Italy, from January 2018 to November 2021. This is a retrospective observational study. Data about the adverse events following immunization (AEFIs) with Gardasil-9® were collected from the Italian Drug Authority database. AEFIs were classified as serious or non-serious accordingly to World Health Organization guidelines, and serious ones underwent causality assessment. During the study period, 266,647 doses of 9vHPVv were administered in Puglia and 22 AEFIs were reported, with a reporting rate (RR) of 8.25 per 100,000 doses. The most reported symptoms were neurological ones (7/22). A total of 5 (22.7%) AEFIs were classified as serious, and 2 of these led to the patient's hospitalization. In one case, permanent impairment occurred. Following causality assessment, only 2 out of 5 serious AEFIs were deemed to be consistently associated with the vaccination (RR: 0.750 per 100,000 doses). The data gathered in our study are similar to the pre-licensure evidence as far as the nature of the AEFIs is concerned. The reporting rate, though, is far lower than the ones described in clinical trials, likely due to the different approach to data collection: in our study, data were gathered via passive surveillance, while pre-marketing studies generally employ active calls for this purpose. Gardasil-9®'s safety profile appears to be favorable, with a low rate of serious adverse events and a risk/benefits ratio pending for the latter.
Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience. [2021]To summarise post-licensure safety surveillance over more than 4 years of routine use of the human papillomavirus-16/18-AS04-adjuvanted vaccine (HPV-16/18 vaccine: Cervarix®, GlaxoSmithKline, Belgium).
[Nine-valent HPV vaccine - new generation of HPV vaccine]. [2018]To evaluate current knowledge about new generation of HPV vaccine - nine-valent vaccine Gardasil9.