NCT06686043

HPV Vaccine, Imiquimod, and Metformin Combination Trial

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 85 (estimated)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: Female
• Age: 18 Years – 64 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Cervical Carcinoma
• Vaginal Carcinoma
• Vulvar Carcinoma
• HPV (Human Papillomavirus)-Associated Carcinoma

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2024-08-23
• Primary completion: 2026-08-23
• Completion: 2028-08-23
• First posted: 2024-11-13
• Last updated: 2024-11-13

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study