Topical Imiquimod Versus Conization to Treat Cervical Intraepithelial Neoplasia (ITIC2)

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

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

Study Overview

• Status: Terminated
• Conditions: Cervical Intraepithelial Neoplasia
• Intervention / Treatment: Drug: Topical Imiquimod; Procedure: Conization

Detailed Description

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 Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion criteria:

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

Exclusion criteria:

1. Adenocarcinoma in situ
2. History of previous conization
3. Malignant disease at the time of inclusion
4. Colposcopy suspicious for invasive disease
5. Pregnancy and lactation period
6. Known allergy or intolerance to IMQ
7. Contraindications to conization or IMQ
8. Symptoms of a clinically relevant disease
9. Known HIV infection
10. Evidence of a clinically significant immunodeficiency
11. Current, reported participation in another experimental, interventional protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Topical Imiquimod; 16 weeks topical Imiquimod	Drug: Topical Imiquimod; 16 weeks; Other Names: Aldara®
Active Comparator: Conization; Large loop excision of the transformation zone	Procedure: Conization; Large loop excision of the transformation zone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HPV clearance	non-inferiority of experimental treatment (Imiquimod) to active control (conization)	6 months after treatment completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of CIN remission/regression and/or CIN persistence/regression after treatment	Histologic outcome	6, 12, and 24 months after treatment completion
HPV clearance		12 and 24 months after treatment completion

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Collaborators: Medical University of Graz; Medical University Innsbruck; Krankenhaus Barmherzige Schwestern Linz; Salzburger Landeskliniken
• Investigators: Principal Investigator: Stephan Polterauer, MD, Medical University of Vienna; Study Director: Stephan Polterauer, MD, Medical University of Vienna

Publications and helpful links

General Publications

• Polterauer S, Reich O, Widschwendter A, Hadjari L, Bogner G, Reinthaller A, Joura E, Trutnovsky G, Ciresa-Koenig A, Ganhoer-Schimboeck J, Boehm I, Berger R, Langthaler E, Aberle SW, Heinze G, Gleiss A, Grimm C. Topical imiquimod compared with conization to treat cervical high-grade squamous intraepithelial lesions: Multicenter, randomized controlled trial. Gynecol Oncol. 2022 Apr;165(1):23-29. doi: 10.1016/j.ygyno.2022.01.033. Epub 2022 Feb 15.

Helpful Links

• Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Anticipated): September 1, 2017
• Study Completion (Anticipated): January 1, 2018

Study Registration Dates

• First Submitted: January 21, 2011
• First Submitted That Met QC Criteria: January 25, 2011
• First Posted (Estimate): January 26, 2011

Study Record Updates

• Last Update Posted (Estimate): November 1, 2016
• Last Update Submitted That Met QC Criteria: October 30, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Cervical Intraepithelial Neoplasia, Imiquimod, conization
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Carcinoma in Situ; Cervical Intraepithelial Neoplasia; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferon Inducers; Imiquimod
• Other Study ID Numbers: ITIC2