A Phase 2 Study of HPV L1 Vaccine in Combination With Imiquimod and Metformin in Cervical, Vaginal, and Vulvar Cancers
Overview
- Phase
- Phase 2
- Intervention
- HPV vaccine, Imiquimod, and metformin combination therapy
- Conditions
- Cervical Carcinoma
- Sponsor
- Baylor College of Medicine
- Enrollment
- 85
- Locations
- 2
- Primary Endpoint
- Progression free survival
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief 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.
Investigators
Jan Sivert Sunde
DIVISION DIRECTOR, GYNECOLOGIC ONCOLOGY Associate Professor
Baylor College of Medicine
Eligibility Criteria
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
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.
Arms & Interventions
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.
Intervention: HPV vaccine, Imiquimod, and metformin combination therapy
Outcomes
Primary Outcomes
Progression free survival
Time Frame: 24 months
Progression-free survival at 24 months will be collected for all patients.
Secondary Outcomes
- Common Toxicity Criteria (CTC)(24 months)
- Identify Immune changes(24 months)