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

    Phase 3
  • Study Type

  • Status

  • Intervention/Treatment

    imiquimod ...
  • Study Participants

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
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 colposcopy-guided biopsies of the uterine cervix will be performed. In addition, rates of CIN persistence/recurrence 6, 12, 18, and 24 months after start of the treatment and rates of negative HPV test results 12 and 24 months after start of the treatment will be evaluated in both treatment groups.

Rationale: The need for a conservative treatment modality for patients diagnosed with CIN is obvious, as many young women need surgical treatment. In this randomized controlled, trial we will investigate the non-inferiority of a topical IMQ treatment compared to surgical standard treatment in selected patients diagnosed with CIN 2/3.
Study Started
May 31
Primary Completion
Sep 30
Study Completion
Jan 31
Last Update
Nov 01

Drug Topical Imiquimod

16 weeks

  • Other names: Aldara®

Procedure Conization

Large loop excision of the transformation zone

Topical Imiquimod Experimental

16 weeks topical Imiquimod

Conization Active Comparator

Large loop excision of the transformation zone


Inclusion criteria:

Women aged ≥18 years diagnosed with histologically verified CIN 3 and women aged ≥ 30 years diagnosed with CIN 2
Satisfactory colposcopy
Signed informed consent
Negative pregnancy test
Appropriate contraception method for fertile women during active study period
Adequate compliance

Exclusion criteria:

Adenocarcinoma in situ
History of previous conization
Malignant disease at the time of inclusion
Colposcopy suspicious for invasive disease
Pregnancy and lactation period
Known allergy or intolerance to IMQ
Contraindications to conization or IMQ
Symptoms of a clinically relevant disease
Known HIV infection
Evidence of a clinically significant immunodeficiency
Current, reported participation in another experimental, interventional protocol
No Results Posted