Treatment of High-Grade Pre-Neoplastic Cervical Lesions (CIN 2/3)

NCT ID: NCT02864147

Last Updated: 2024-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2022-11-22

Brief Summary

This is a randomized Phase II, three arm control trial in patients with Cervical Intraepithelial Neoplasia (CIN) 2/3 high grade cervical dysplasia. Patients with CIN 2/3 meeting eligibility criteria will have cervical biopsy specimens centrally reviewed by study pathologist to confirm diagnosis. HPV DNA test and HPV 16/18 genotyping will be performed from endocervical cytobrush samples to determine HPV status associated with the dysplasia.

Patients who have CIN 2/3 with HPV+ disease will be enrolled in this study. Patients will be randomized to one of three arms: observation only (control), imiquimod only, imiquimod + 9-valent HPV vaccine.

Detailed Description

The primary objectives of this study are as follows:

• 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 HPV Vaccine + Imiquimod group compared to control,
• 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.

The secondary objectives of this study are as follows:

• 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,
• To assess HPV clearance in each group,
• To assess treatment tolerability.

In addition to the primary and secondary objectives of this study, there additional exploratory/correlative objectives. The exploratory/correlative objectives are as follows:

• To assess T cell infiltration in post-treatment cervical biopsies and endocervical cytobrush samples,
• To assess HPV16 E7 immunity in CD4/CD8 T cells.

Conditions

Cervical Intraepithelial Neoplasia; Cervical Dysplasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

imiquimod + 9-valent HPV vaccine

Participants randomized to the imiquimod + 9-valent HPV vaccine group will receive instruction on imiquimod self application (16 week course) at the baseline visit. In addition, all women (regardless of age) will be administered a dose of the HPV vaccine on day of enrollment (regardless of previous HPV vaccination history). Women previously unvaccinated will receive an additional booster dose at 8 weeks.

Group Type: EXPERIMENTAL

9-valent HPV vaccine

Intervention Type: DRUG

All women (regardless of age) will be administered a dose of the HPV vaccine on day of enrollment (regardless of previous HPV vaccination history). Women previously unvaccinated will receive an additional booster dose at 8 weeks.

Imiquimod

Intervention Type: DRUG

At the baseline visit, this group will be instructed about the correct method of self-application of imiquimod 6.25mg as a vaginal suppository and receive a 16 week course of the drug.

imiquimod only

Participants randomized to the imiquimod only group will receive instruction on imiquimod self application (16 week course) at the baseline visit.

Group Type: ACTIVE_COMPARATOR

Imiquimod

Intervention Type: DRUG

At the baseline visit, this group will be instructed about the correct method of self-application of imiquimod 6.25mg as a vaginal suppository and receive a 16 week course of the drug.

observation only (control)

Participants randomized to the control group will only be observed and will receive no intervention.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

9-valent HPV vaccine

All women (regardless of age) will be administered a dose of the HPV vaccine on day of enrollment (regardless of previous HPV vaccination history). Women previously unvaccinated will receive an additional booster dose at 8 weeks.

Intervention Type: DRUG

Imiquimod

At the baseline visit, this group will be instructed about the correct method of self-application of imiquimod 6.25mg as a vaginal suppository and receive a 16 week course of the drug.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients must have untreated cervical biopsy-proven, CIN 2/3 ectocervical lesion(s).
• Patients must have satisfactory colposcopy with visualization of the entire transformation zone or a negative endocervical curettage if colposcopy is unsatisfactory.
• Patients must be high-risk HPV+ as determined by commercially available DNA hybridization test which tests for 13 high-risk HPV types.
• All Patients must have a histologic diagnosis of CIN 2,3 cervical lesion(s) confirmed by a study pathologist within past 10 weeks.
• Patients must have signed an approved informed consent.
• Patients 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.
• Patients must be at least 18 years of age based on previous and current cervical cancer screening guidelines.
• Patients must be fluent in speaking English or Spanish.

Exclusion Criteria

• Patients with unsatisfactory colposcopy* (unable to visualize entire transformation zone) or evidence of endocervical disease defined as CIN 2/3 diagnosed on endocervical curettage.

*Patients with unsatisfactory colposcopy but negative endocervical curettage are eligible

• Patients with a history of invasive cervical cancer
• Patients 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. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
• Patients with any unstable medical issue (including cardiac issues as above, active treatment for pulmonary embolism, CVA, renal or hepatic insufficiency, active infection/sepsis requiring IV antibiotics).
• Patients who have an uncontrolled seizure disorder, or active neurological disease.
• Patients known to be seropositive for HIV and active hepatitis, even if liver function studies are in the normal range. Patients otherwise immunocompromised will also be excluded (chronic steroid use, taking immunosuppressive medications).
• Pregnant or breastfeeding patients.
• Patients who have had a total hysterectomy (removal of uterus and cervix) or trachelectomy (removal of cervix).
• Patients with a known hypersensitivity to imiquimod. Patients with a known hypersensitivity to any prophylactic HPV vaccine or severe allergic reactions yeast (vaccine component).
• Patients 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alessandro D Santin, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University School of Medicine Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Gynecologic Oncology

Sangini S Sheth, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Yale University School of Medicine Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Gynecologic Specialties

Locations

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

000

Identifier Type: OTHER

Identifier Source: secondary_id

1603017415

Identifier Type: -

Identifier Source: org_study_id