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

Phase 2

Completed

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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
imiquimod + 9-valent HPV vaccine	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.
imiquimod only	Imiquimod	Participants randomized to the imiquimod only group will receive instruction on imiquimod self application (16 week course) at the baseline visit.
imiquimod + 9-valent HPV vaccine	Imiquimod	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.

Primary Outcome Measures

Name	Time	Method
Incidence of Objective Response	Between weeks 20 and 24 (approximately week 22)	The major parameters of objective response to be assessed include treatment efficacy defined as histologic regression of cervical dysplasia to CIN 1 or less after the end of imiquimod treatment, HPV clearance and treatment tolerance. Objective response will be categorized as 'yes' or 'no' and included in the evaluations are the following criteria: * Histologic regression (HR): Histologic regression of all index lesions to CIN 1 or less after end of imiquimod treatment period. * Histologic remission (HM): Complete regression of cervical dysplasia at all index biopsy sites after end of imiquimod treatment period. * Persistent Disease (PR): One or more index lesions persists with CIN 2,3 high grade dysplasia or new lesions are identified colposcopically and histologically confirmed to be CIN 2,3. * Progressive Disease (PD): Worsening histology of an index lesion.

Secondary Outcome Measures

Name	Time	Method
Incidence of HPV Clearance	Between weeks 20 and 24 (approximately week 22)	HPV Clearance will be categorized as 'yes' or 'no' and the evaluations are the following criteria: HPV clearance will be measured by both the Roche cobas HPV Test utilized by pathology concomitant with the pap test at final study visit which assesses for presence of 14 high risk HPV types as well as HPV 16/18 genotyping performed by Santin Lab.