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Trial record 42 of 80 for:    "Cervix Disease" | "Vaccines"

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

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ClinicalTrials.gov Identifier: NCT02864147
Recruitment Status : Recruiting
First Posted : August 11, 2016
Last Update Posted : June 19, 2019
Sponsor:
Information provided by (Responsible Party):
Yale University

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.


Condition or disease Intervention/treatment Phase
Cervical Intraepithelial Neoplasia Cervical Dysplasia Drug: 9-valent HPV vaccine Drug: Imiquimod Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Treatment of High-Grade Pre-Neoplastic Cervical Lesions (CIN 2/3) Using a Novel "Prime and Pull" Strategy
Study Start Date : July 2016
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Imiquimod

Arm Intervention/treatment
Experimental: 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.
Drug: 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.

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.

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

No Intervention: observation only (control)
Participants randomized to the control group will only be observed and will receive no intervention.



Primary Outcome Measures :
  1. Incidence of Objective Response [ Time Frame: 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 :
  1. Incidence of HPV Clearance [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02864147


Contacts
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Contact: Alessandro D Santin, MD 203-737-4450 alessandro.santin@yale.edu
Contact: Sangini S Sheth, MD, MPH 203-785-5545 sangini.sheth@yale.edu

Locations
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United States, Connecticut
Smilow Cancer Hospital at Yale New Haven Recruiting
New Haven, Connecticut, United States, 06510
Contact: Alessandro D Santin, M.D.    203-737-4450    alessandro.santin@yale.edu   
Contact: Lisa Baker, RN, BSN, OCN    203-785-6398    lisa.baker@yale.edu   
Principal Investigator: Alessandro Santin, M.D.         
Sponsors and Collaborators
Yale University
Investigators
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Principal Investigator: Alessandro D Santin, MD Yale University School of Medicine Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Gynecologic Oncology
Principal Investigator: Sangini S Sheth, MD, MPH Yale University School of Medicine Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Gynecologic Specialties

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02864147     History of Changes
Other Study ID Numbers: 1603017415
First Posted: August 11, 2016    Key Record Dates
Last Update Posted: June 19, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Uterine Cervical Diseases
Vaccines
Cervical Intraepithelial Neoplasia
Uterine Cervical Dysplasia
Neoplasms
Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Precancerous Conditions
Uterine Diseases
Genital Diseases, Female
Imiquimod
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Antineoplastic Agents
Interferon Inducers