Clinical Trial: Topical Imiquimod Versus Conization to Treat Cervical Intraepithelial Neoplasia

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: ITIC2 Trial - Topical Imiquimod Versus Conization to Treat Cervical Intraepithelial Neoplasia: Randomised Controlled, Non-inferiority Trial

Brief Summary: The purpose of this study is to investigate the non-inferiority of a topical Imiquimod therapy in patients with persistent CIN 2/3 when compared to standard therapy, i.e. conization A randomized, controlled, non-inferiority AGO-Austria trial

Detailed Summary:

Background: Alternatives to surgery are needed for the treatment of cervical intraepithelial neoplasia (CIN). CIN is associated with persistent human papillomavirus (HPV) infection and is known to be a potential precursor of cervical cancer. The incidence of CIN has been increasing during the last decades, especially among young women. Patients diagnosed with (persistent) high-grade CIN (CIN2/3) are treated with conization. Conization can be regarded as a safe procedure but peri- and postoperative complications (infections, bleeding, preterm birth) occur. This raises the need for a conservative treatment alternative for patients with high-grade CIN. Preliminary data: Imiquimod (IMQ), a toll-like receptor 7 agonist, is an immune modulating substance approved for the therapy of superficial skin lesions (e.g. basalioma, actinic keratosis) and HPV associated disease (e.g. anogenital condylomata acuminata and vulvar intraepithelial neoplasia). In a randomized, placebo-controlled phase II trial, we previously showed that topical IMQ therapy is an efficacious and feasible treatment for selected patients with CIN 2/3. Methods: In the present open, randomized, non-inferiority trial 500 women with CIN 2/3 will be included. This non-profit, patient-oriented clinical research project will be conducted as an Austrian Gynecologic Oncology Group (AGO-Austria) trial. Participants will be randomized to either 16 weeks treatment with topical IMQ (new treatment) or to standard therapy i.e. conization (active control). This study investigates the non-inferiority of the new treatment, compared to surgical standard treatment. The primary endpoint is the rate of successful treatment, defined as negative HPV test result six months after treatment start. Six months after start of therapy the primary study endpoint is assessed using HPV genotyping. In addition clinical examinations including colposcopy, HPV genotyping, cytology, and if indicated
Sponsor: Medical University of Vienna

Current Primary Outcome: HPV clearance [ Time Frame: 6 months after treatment completion ]

non-inferiority of experimental treatment (Imiquimod) to active control (conization)


Original Primary Outcome: Effectiveness [ Time Frame: 4 weeks after end of treatment of all 220 participants, up to 33 month after study initiation ]

Complete CIN Remission


Current Secondary Outcome:

  • Rates of CIN remission/regression and/or CIN persistence/regression after treatment [ Time Frame: 6, 12, and 24 months after treatment completion ]
    Histologic outcome
  • HPV clearance [ Time Frame: 12 and 24 months after treatment completion ]


Original Secondary Outcome:

  • HPV clearance [ Time Frame: after 8 weeks of treatment completion ]
    HPV-clearance rate
  • Cellular and molecular mechanisms of HPV immune evasion [ Time Frame: before and after treatment ]


Information By: Medical University of Vienna

Dates:
Date Received: January 21, 2011
Date Started: May 2013
Date Completion: January 2018
Last Updated: October 30, 2016
Last Verified: October 2016