HPV Vaccine, Imiquimod, and Metformin Combination Trial (HPV-VIM)

November 11, 2024 updated by: Jan Sivert Sunde, Baylor College of Medicine

A Phase 2 Study of HPV L1 Vaccine in Combination With Imiquimod and Metformin in Cervical, Vaginal, and Vulvar Cancers

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The goal of this clinical trial is to determine whether stimulating tumor immunity through sequential, targeted intratumoral vaccinations using the FDA-approved quadrivalent HPV-L1 antigen vaccine, in combination with chemotherapy, radiotherapy, pembrolizumab, imiquimod, and metformin, improves outcomes for patients with locally advanced cervical, vaginal, or vulvar carcinoma. The primary objective is to assess the impact of this approach on 24-month progression-free survival when used alongside whole pelvic radiotherapy, chemotherapy, and brachytherapy.

The trial will also monitor the safety and potential side effects of combining intratumoral HPV vaccination with topical imiquimod and oral metformin during and after chemoradiation. Additionally, researchers aim to evaluate specific immune markers to understand how these treatments boost the immune system and enhance the effects of standard care.

Participants will:

Receive intratumoral HPV vaccinations during the 2nd and 4th week of radiation, and after completing radiation at weeks 8, 10, 12, and 16.

Have blood samples taken, tumor cells brushed, 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.

Throughout the trial, immune biomarker assays will be conducted at the beginning, middle, and end of treatment to measure markers such as CD4, CD8, NK, TNF alpha and beta, IL2, HPV viral load, TGF Beta, Ki67, and IgG. Blood tests will also be done for IgG L1 and L2, E6 and E7, and a CBC, to track immune changes across the three treatment groups.

Study Type

Interventional

Enrollment (Estimated)

85

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77054
        • Recruiting
        • Harris Health Smith Clinic
        • Contact:
          • Jan S Sunde, MD
          • Phone Number: 206-778-9253
          • Email: sunde@bcm.edu
        • Principal Investigator:
          • Jan S Sunde, MD
        • Contact:
      • Houston, Texas, United States, 77054
        • Not yet recruiting
        • Baylor St. Luke's Medical Center- Dan L. Duncan Comprehensive Cancer Center
        • Contact:
        • Contact:
          • Jan S Sunde, MD
          • Phone Number: 206-778-9253
          • Email: sunde@bcm.edu
        • Principal Investigator:
          • Jan S Sunde, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants must have histologically confirmed locally advanced or metastatic cervical carcinoma (Stage IB2-IVB), vaginal, or vulvar carcinoma (Stage II-IVB), AND not be considered a primary surgical candidate. Patients offered neoadjuvant therapy may be enrolled if they respond and receive chemoradiation.
  • Participants must have measurable disease, per Recist criteria. See Section 12 (Measurement of Effect) for the evaluation of measurable disease. Radiological evaluation shall occur within approximately 30 days prior to enrollment initiation and start of radiation.
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Participants must be ≥ 18 years of age
  • Participants must have adequate organ function within 28 days of registration, defined as follows: - Absolute neutrophil count ≥ 1,500/µL - Platelets ≥ 100,000/µL - Hemoglobin ≥ 9 g/dL - Serum creatinine ≤ 1.5 x upper limit of normal (ULN) - Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN - Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
  • Participants receiving corticosteroids may continue as long as their dose is stable for at least 4 weeks prior to initiating protocol therapy.
  • Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
  • Female participants of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. Females of non-childbearing potential is defined as follows (by other than medical reasons): - ≥45 years of age and has not had menses for >1 year, post-hysterectomy, post-bilateral oophorectomy, post external beam radiation of 6 Gy to the pelvis, or post-tubal ligation.
  • Participants must agree to not breastfeed during the study.
  • Participants must be able to understand the study procedures and agree to participate in the study by providing written informed consent
  • Participants must be eligible for chemoradiation treatment in the opinion of the treating investigator.
  • Participants who are HIV+ must have CD4 counts >200/dL and demonstrate documented Highly active antiretroviral therapy (HAART) compliance m. Participant must have CT (chest/abdomen/pelvis) or PET-CT, within 56 days of registration.
  • Participants must be newly diagnosed.
  • Standard chemoradiation using external beam radiation therapy (EBRT) and brachytherapy is permitted for cervical or vaginal carcinoma, and chemoradiation with EBRT for vulvar carcinoma. A lesion must be readily accessible for intratumoral tumor injection.
  • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Exclusion Criteria:

  • Patients who are receiving any other investigational agents.
  • Patients who have untreated, new or progressive brain metastases or leptomeningeal disease.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study.
  • Patients with uncontrolled intercurrent illness.
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because cervical carcinoma or vulva carcinoma patients have undergone treatment rendering the patient infertile. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cervical carcinoma or vulva carcinoma, breastfeeding should be discontinued.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment group
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.
Drug: HPV vaccine, Imiquimod, and metformin combination therapy
Participants in the treatment arm will have visits during the 2nd and 4th weeks of radiation, and then at weeks 8, 10, 12, and 16 after radiation. At each visit, a blood sample will be taken, and tumor cells collected using a cytobrush (or directly from the tumor for vulvar cancer). An HPV vaccine will be injected into the tumor, imiquimod cream will be applied topically, and participants will receive a subcutaneous vaccine shot. They will also take metformin tablets twice daily for two weeks and apply imiquimod cream at home three nights per week. Follow-up PET/CT scans will occur at week 20 and two years post-treatment, with exams every three months for two years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 24 months
Progression-free survival at 24 months will be collected for all patients.
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Common Toxicity Criteria (CTC)
Time Frame: 24 months
Discontinuation rate of medications during treatments due to potential side effects
24 months
Identify Immune changes
Time Frame: 24 months
Immune biomarker assays will be taken at the beginning, middle, and end of the treatment to measure the following markers: CD4, CD8, NK, TNF alpha and beta, IL2, HPV viral load, TGF Beta, Ki67, IGg. We will also do blood tests to test for IGg L1 and L2, E6 and E7 and a CBC. These markers combined were chosen to identify specific immune changes of the three medication treatment groups.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Baylor College of Medicine

Collaborators

Harris Health
Baylor St. Luke's Medical Center
Dan L Duncan Comprehensive Cancer Center

Investigators

  • Principal Investigator: Jan S Sunde, MD, Baylor College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 23, 2024

Primary Completion (Estimated)

August 23, 2026

Study Completion (Estimated)

August 23, 2028

Study Registration Dates

First Submitted

November 3, 2024

First Submitted That Met QC Criteria

November 11, 2024

First Posted (Estimated)

November 13, 2024

Study Record Updates

Last Update Posted (Estimated)

November 13, 2024

Last Update Submitted That Met QC Criteria

November 11, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-54674

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The study team will deposit deidentified data in on-line database

IPD Sharing Time Frame

Within 6 months of study completion.

IPD Sharing Access Criteria

Public access database

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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