Imiquimod with or without 9-Valent HPV Vaccine in Treating Patients with High-Grade Pre-neoplastic Cervical Lesions

Status: Active

Description

This phase II trial studies how well imiquimod with or without 9-valent human papillomavirus (HPV) vaccine work in treating patients with high-grade pre-neoplastic cervical lesions. Imiquimod may help to improve patients' immune system. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of cancer. It is not yet known whether giving imiquimod with or without 9-valent HPV vaccine may work better in treating patients with cervical lesions.

Eligibility Criteria

Inclusion Criteria

  • Subjects must have untreated cervical biopsy-proven, CIN 2/3 ectocervical lesion(s).
  • Subjects must have satisfactory colposcopy with visualization of the entire transformation zone or a negative endocervical curettage if colposcopy is unsatisfactory.
  • Subjects must be high-risk HPV+ as determined by commercially available deoxyribonucleic acid (DNA) hybridization test which tests for 13 high-risk HPV types.
  • All subjects must have a histologic diagnosis of CIN 2,3 cervical lesion(s) confirmed by a study pathologist within past 10 weeks.
  • Subjects must have signed an approved informed consent.
  • Subjects of childbearing potential must have a negative urine pregnancy test within 7 days prior to the study entry and be practicing an effective form of contraception.
  • Subjects must be fluent in speaking English or Spanish.

Exclusion Criteria

  • Subjects with unsatisfactory colposcopy* (unable to visualize entire transformation zone) or evidence of endocervical disease defined as CIN 2/3 diagnosed on endocervical curettage. *Subjects with unsatisfactory colposcopy but negative endocervical curettage are eligible
  • Subjects with a history of invasive cervical cancer.
  • Subjects with a history of other invasive malignancies, with the exception of non-melanoma skin cancers are excluded if there is any evidence of other malignancy being present within the last five years. Subjects are also excluded if their previous cancer treatment contraindicates this protocol therapy.
  • Subjects with any unstable medical issue (including cardiac issues as above, active treatment for pulmonary embolism, cerebrovascular accident [CVA], renal or hepatic insufficiency, active infection/sepsis requiring IV antibiotics).
  • Subjects who have an uncontrolled seizure disorder, or active neurological disease.
  • Subjects known to be seropositive for human immunodeficiency virus (HIV) and active hepatitis, even if liver function studies are in the normal range. Subjects otherwise immunocompromised will also be excluded (chronic steroid use, taking immunosuppressive medications).
  • Pregnant or breastfeeding subjects.
  • Subjects who have had a total hysterectomy (removal of uterus and cervix) or trachelectomy (removal of cervix).
  • Subjects with a known hypersensitivity to imiquimod. Subjects with a known hypersensitivity to any prophylactic HPV vaccine or severe allergic reactions to yeast (vaccine component).
  • Subjects who have received their first dose of HPV vaccine < 4 weeks ago or their second dose < 12 weeks ago.
  • Known hypersensitivity or prior intravaginal treatment with imiquimod.

Locations & Contacts

Connecticut

New Haven
Yale University
Status: Active
Contact: Alessandro D. Santin
Phone: 203-737-4450
Email: alessandro.santin@yale.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine treatment efficacy defined as histologic regression to cervical intraepithelial neoplasia (CIN) 1 or less at weeks 20-24 (4 to 8 weeks after the end of imiquimod treatment) in the HPV vaccine + Imiquimod group compared to control.

II. To determine treatment efficacy defined as histologic regression to CIN 1 or less at weeks 20-24 (4 to 8 weeks after the end of imiquimod treatment) in the Imiquimod group compared to control.

SECONDARY OBJECTIVES:

I. To assess complete regression (i.e., histologic remission) at weeks 20-24 (4 to 8 weeks after the end of imiquimod treatment) in each group.

II. To assess HPV clearance in each group.

III. To assess treatment tolerability.

EXPLORATORY OBJECTIVES:

I. To assess T cell infiltration in post-treatment cervical biopsies and endocervical cytobrush samples.

II. To assess HPV16 E7 immunity in CD4/CD8 T cells.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients undergo observation.

ARM II: Patients receive imiquimod via vaginal suppository every week for 16 weeks.

ARM III: Patients receive imiquimod via vaginal suppository every week for 16 weeks. Patients also receive recombinant human papillomavirus nonavalent vaccine intramuscularly (IM) at baseline and week 8.

After completion of study treatment, patients are followed up at week 22, and at 3 and 6 months.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Yale University

Principal Investigator
Alessandro D. Santin

Trial IDs

Primary ID 1603017415
Secondary IDs NCI-2018-01947
Clinicaltrials.gov ID NCT02864147