HPV Vaccine, Imiquimod, and Metformin Combination Trial

NCT06686043 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: H-54674
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

metformin; HPV; Imiquimod; Human Papillomavirus 9-valent Vaccine; Recombinant; Cytobrush; cervical cancer; vaginal cancer; vulvar cancer; chemoradiation; tumor; immunotherapy; metastatic; intratumoral; Endometrial cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression-free survival at 24 months will be collected for all patients.

  24 months

Secondary Outcomes (2)

• Common Toxicity Criteria (CTC)

  24 months

• Identify Immune changes

  24 months

Study Arms (1)

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.

Drug: HPV vaccine, Imiquimod, and metformin combination therapy

Interventions

HPV vaccine, Imiquimod, and metformin combination therapy DRUG

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.

Treatment group

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Harris Health: collaborator
• Dan L Duncan Comprehensive Cancer Center: collaborator
• Baylor St. Luke's Medical Center: collaborator

Study Sites (2)

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

Houston, Texas, 77054, United States

NOT YET RECRUITING

Harris Health Smith Clinic

Houston, Texas, 77054, United States

RECRUITING

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MeSH Terms

Conditions

Uterine Cervical Neoplasms; Vaginal Neoplasms; Vulvar Neoplasms; Papillomavirus Infections; Neoplasms; Neoplasm Metastasis; Endometrial Neoplasms

Interventions

Papillomavirus Vaccines; Imiquimod

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Vaginal Diseases; Vulvar Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jan S Sunde, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Keneshia K Lane, B.A.

CONTACT

832-826-8071; Keneshia.Lane@bcm.edu

Kathleen Pennington, Ph.D

CONTACT

832-824-4190; kathleen.pennington@bcm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: DIVISION DIRECTOR, GYNECOLOGIC ONCOLOGY Associate Professor

Study Record Dates

• First Submitted: November 3, 2024
• First Posted: November 13, 2024
• Study Start: August 23, 2024
• Primary Completion (Estimated): August 23, 2026
• Study Completion (Estimated): August 23, 2028
• Last Updated: November 13, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Within 6 months of study completion.
• Access Criteria: Public access database

Locations

US (2)