Cervical CarcinomaPhase 2HPV-VIMNCT06686043
HPV Vaccine, Imiquimod, and Metformin Combination Trial
A Phase 2 study testing HPV vaccine, Imiquimod, and metformin combination therapy in people with Cervical Carcinoma and Vaginal Carcinoma, run by Baylor College of Medicine at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 years, women only
- Conditions the study is for
- Cervical Carcinoma, Vaginal Carcinoma, Vulvar Carcinoma
- What is being tested?
- HPV vaccine, Imiquimod, and metformin combination therapy
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Aug 2024to 23 Aug 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Not yet recruiting
Baylor St. Luke's Medical Center- Dan L. Duncan Comprehensive Cancer Center
Houston, Texas, 77054
Keneshia K Lane, B.A., 832-826-8071, Keneshia.Lane@bcm.edu
Jan S Sunde, MD, 206-778-9253, sunde@bcm.edu
- Recruiting
Harris Health Smith Clinic
Houston, Texas, 77054
Keneshia K Lane, B.A, 832-826-8071, Keneshia.Lane@bcm.edu
Jan S Sunde, MD, 206-778-9253, sunde@bcm.edu
About this study
Official title: 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.
Read more
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.
Read the 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
- Being tested
- HPV vaccine, Imiquimod, and metformin combination therapy
- Keywords
- metformin, HPV, Imiquimod, Human Papillomavirus 9-valent Vaccine, Recombinant, Cytobrush, cervical cancer, vaginal cancer, vulvar cancer, chemoradiation, tumor, immunotherapy, metastatic, intratumoral, Endometrial cancer
- Medical subject headings
- Uterine Cervical Neoplasms, Vaginal Neoplasms, Vulvar Neoplasms, Papillomavirus Infections, Neoplasms, Neoplasm Metastasis, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HPV vaccine, Imiquimod, and metformin combination therapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | 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. Receives: Drug: HPV vaccine, Imiquimod, and metformin combination therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Progression-free survival at 24 months will be collected for all patients.
Measured: 24 months
Secondary outcomes (2)
Common Toxicity Criteria (CTC)
Discontinuation rate of medications during treatments due to potential side effects
Measured: 24 months
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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2024
- Study start23 Aug 2024
- Primary completion23 Aug 2026 (estimated)
- Study completion23 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (55)Papers the sponsor has linked to this study.
- Other trials for Cervical CarcinomaStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Harris Health, Dan L Duncan Comprehensive Cancer Center, Baylor St. Luke's Medical Center
- Responsible party
- Principal investigator, Jan Sivert Sunde, Baylor College of Medicine
- Investigators
- Jan S Sunde, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06686043
- Sponsor's protocol ID
- H-54674
- Acronym
- HPV-VIM
- Status last verified
- Nov 2024
- First submitted
- 3 Nov 2024
- Last updated
- 13 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The study team will deposit deidentified data in on-line database
Publications
Tantipalakorn C, Robertson G, Marsden DE, Gebski V, Hacker NF. Outcome and patterns of recurrence for International Federation of Gynecology and Obstetrics (FIGO) stages I and II squamous cell vulvar cancer. Obstet Gynecol. 2009 Apr;113(4):895-901. doi: 10.1097/AOG.0b013e31819b413f.
PubMed 19305336Reedy M, Jonnalagadda S, Palle K. Case Report: Intra-Tumoral Vaccinations of Quadrivalent HPV-L1 Peptide Vaccine With Topical TLR-7 Agonist Following Recurrence: Complete Resolution of HPV-HR-Associated Gynecologic Squamous Cell Carcinomas in Two Patients. Pathol Oncol Res. 2021 Dec 20;27:1609922. doi: 10.3389/pore.2021.1609922. eCollection 2021.
PubMed 34987310Mondini M, Nizard M, Tran T, Mauge L, Loi M, Clemenson C, Dugue D, Maroun P, Louvet E, Adam J, Badoual C, Helley D, Dransart E, Johannes L, Vozenin MC, Perfettini JL, Tartour E, Deutsch E. Synergy of Radiotherapy and a Cancer Vaccine for the Treatment of HPV-Associated Head and Neck Cancer. Mol Cancer Ther. 2015 Jun;14(6):1336-45. doi: 10.1158/1535-7163.MCT-14-1015. Epub 2015 Apr 1.
PubMed 25833837Mu J, Lei L, Zheng Y, Li D, Li J, Fu Y, Wang G, Liu Y. Comparative study of subcutaneous, intramuscular, and oral administration of bovine pathogenic Escherichia coli bacterial ghost vaccine in mice. Front Immunol. 2022 Nov 14;13:1008131. doi: 10.3389/fimmu.2022.1008131. eCollection 2022.
PubMed 36451816Afzal MZ, Mercado RR, Shirai K. Efficacy of metformin in combination with immune checkpoint inhibitors (anti-PD-1/anti-CTLA-4) in metastatic malignant melanoma. J Immunother Cancer. 2018 Jul 2;6(1):64. doi: 10.1186/s40425-018-0375-1.
PubMed 29966520Wu Z, Zhang C, Najafi M. Targeting of the tumor immune microenvironment by metformin. J Cell Commun Signal. 2022 Sep;16(3):333-348. doi: 10.1007/s12079-021-00648-w. Epub 2021 Oct 5.
PubMed 34611852Ma R, Yi B, Riker AI, Xi Y. Metformin and cancer immunity. Acta Pharmacol Sin. 2020 Nov;41(11):1403-1409. doi: 10.1038/s41401-020-00508-0. Epub 2020 Aug 31.
PubMed 32868904Tselikas L, Dardenne A, de Baere T, Faron M, Ammari S, Farhane S, Suzzoni S, Danlos FX, Raoult T, Susini S, Al Shatti N, Mouraud S, Deschamps F, Kobe A, Delpla A, Roux C, Baldini C, Soria JC, Barlesi F, Massard C, Robert C, Champiat S, Marabelle A. Feasibility, safety and efficacy of human intra-tumoral immuno-therapy. Gustave Roussy's initial experience with its first 100 patients. Eur J Cancer. 2022 Sep;172:1-12. doi: 10.1016/j.ejca.2022.05.024. Epub 2022 Jun 18.
PubMed 35724442van de Sande AJM, Kengsakul M, Koeneman MM, Jozwiak M, Gerestein CG, Kruse AJ, van Esch EMG, de Vos van Steenwijk PJ, Muntinga CLP, Bramer WM, van Doorn HC, van Kemenade FJ, van Beekhuizen HJ. The efficacy of topical imiquimod in high-grade cervical intraepithelial neoplasia: A systematic review and meta-analysis. Int J Gynaecol Obstet. 2024 Jan;164(1):66-74. doi: 10.1002/ijgo.14953. Epub 2023 Jun 23.
PubMed 37350560Rosales R, Lopez-Contreras M, Rosales C, Magallanes-Molina JR, Gonzalez-Vergara R, Arroyo-Cazarez JM, Ricardez-Arenas A, Del Follo-Valencia A, Padilla-Arriaga S, Guerrero MV, Pirez MA, Arellano-Fiore C, Villarreal F. Regression of human papillomavirus intraepithelial lesions is induced by MVA E2 therapeutic vaccine. Hum Gene Ther. 2014 Dec;25(12):1035-49. doi: 10.1089/hum.2014.024.
PubMed 25275724Marei A, Nofal A, Alakad R, Abdel-Hady A. Combined bivalent human papillomavirus vaccine and Candida antigen versus Candida antigen alone in the treatment of recalcitrant warts. J Cosmet Dermatol. 2020 Mar;19(3):758-762. doi: 10.1111/jocd.13077. Epub 2019 Jul 22.
PubMed 31328869Mori V, DuComb EA, Wagner S, Khan F, Bates JHT, Kinsey CM. Visualizing intratumoral injections in lung tumors by endobronchial ultrasound. J Cancer. 2023 Feb 22;14(4):544-553. doi: 10.7150/jca.81793. eCollection 2023.
PubMed 37057292Kidner TB, Morton DL, Lee DJ, Hoban M, Foshag LJ, Turner RR, Faries MB. Combined intralesional Bacille Calmette-Guerin (BCG) and topical imiquimod for in-transit melanoma. J Immunother. 2012 Nov-Dec;35(9):716-20. doi: 10.1097/CJI.0b013e31827457bd.
PubMed 23090081Omland SH, Ejlertsen JS, Krustrup D, Christensen RL, Svane IM, Olesen UH, Haedersdal M. Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional Laser. Cancers (Basel). 2022 Nov 25;14(23):5815. doi: 10.3390/cancers14235815.
PubMed 36497301Ponce S, Cedres S, Ricordel C, Isambert N, Viteri S, Herrera-Juarez M, Martinez-Marti A, Navarro A, Lederlin M, Serres X, Zugazagoitia J, Vetrhus S, Jaderberg M, Hansen TB, Levitsky V, Paz-Ares L. ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment. J Immunother Cancer. 2023 Sep;11(9):e007552. doi: 10.1136/jitc-2023-007552.
PubMed 37661097