Topical Imiquimod Versus Conization to Treat Cervical Intraepithelial Neoplasia

Cervical Intraepithelial Neoplasia Clinical Trial

— ITIC2  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01283763
• Other study ID #: ITIC2
• Status: Terminated
• Phase: Phase 3
• First received: January 21, 2011
• Last updated: October 30, 2016
• Start date: May 2013
• Est. completion date: January 2018

Study information

• Verified date: October 2016
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food Safety
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 95
• Est. completion date: January 2018
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma in Situ
• Cervical Intraepithelial Neoplasia
• Neoplasms

Intervention

Drug:
• Topical Imiquimod
16 weeks

Procedure:
• Conization
Large loop excision of the transformation zone

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (5)

Lead Sponsor	Collaborator
Medical University of Vienna	Krankenhaus Barmherzige Schwestern Linz, Medical University Innsbruck, Medical University of Graz, Salzburger Landeskliniken

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HPV clearance	non-inferiority of experimental treatment (Imiquimod) to active control (conization)	6 months after treatment completion	No
Secondary	Rates of CIN remission/regression and/or CIN persistence/regression after treatment	Histologic outcome	6, 12, and 24 months after treatment completion	No
Secondary	HPV clearance		12 and 24 months after treatment completion	No

External Links

•   Austrian Gynecologic Oncology group (AGO-Austria)
•   Medical University of Vienna