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.
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
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.
Single group
HPV vaccine, Imiquimod, and metformin combination therapy
DrugParticipants 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.
Progression free survival
Progression-free survival at 24 months will be collected for all patients.
Common Toxicity Criteria (CTC)
Discontinuation rate of medications during treatments due to potential side effects
Identify Immune changes
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.
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Baylor College of Medicine
Lead sponsor
Harris Health
Collaborator
Dan L Duncan Comprehensive Cancer Center
Collaborator
Baylor St. Luke's Medical Center
Collaborator
