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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Medical University of Vienna
Sponsor:
Collaborators:
Medical University of Graz
Medical University Innsbruck
Krankenhaus Barmherzige Schwestern Linz
Salzburger Landeskliniken
Information provided by (Responsible Party):
Stephan Polterauer, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01283763
First received: January 21, 2011
Last updated: July 15, 2013
Last verified: July 2013

January 21, 2011
July 15, 2013
May 2013
September 2017   (final data collection date for primary outcome measure)
HPV clearance [ Time Frame: 6 months after treatment completion ] [ Designated as safety issue: No ]
non-inferiority of experimental treatment (Imiquimod) to active control (conization)
Effectiveness [ Time Frame: 4 weeks after end of treatment of all 220 participants, up to 33 month after study initiation ] [ Designated as safety issue: No ]
Complete CIN Remission
Complete list of historical versions of study NCT01283763 on ClinicalTrials.gov Archive Site
  • Rates of CIN remission/regression and/or CIN persistence/regression after treatment [ Time Frame: 6, 12, and 24 months after treatment completion ] [ Designated as safety issue: No ]
    Histologic outcome
  • HPV clearance [ Time Frame: 12 and 24 months after treatment completion ] [ Designated as safety issue: No ]
  • HPV-clearance [ Time Frame: after 8 weeks of treatment completion ] [ Designated as safety issue: No ]
    HPV-clearance rate
  • Cellular and molecular mechanisms of HPV immune evasion [ Time Frame: before and after treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Cervical Intraepithelial Neoplasia
  • Drug: Topical Imiquimod
    16 weeks
    Other Name: Aldara®
  • Procedure: Conization
    Large loop excision of the transformation zone
  • Experimental: Topical Imiquimod
    16 weeks topical Imiquimod
    Intervention: Drug: Topical Imiquimod
  • Active Comparator: Conization
    Large loop excision of the transformation zone
    Intervention: Procedure: Conization
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
500
January 2018
September 2017   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact: Stephan Polterauer, M.D. +43140400 ext 2962 stephan.polterauer@meduniwien.ac.at
Contact: Stephan Polterauer +43140400 ext 2962 stephan.polterauer@meduniwien.ac.at
Austria
 
NCT01283763
ITIC2
Yes
Stephan Polterauer, Medical University of Vienna
Medical University of Vienna
  • Medical University of Graz
  • Medical University Innsbruck
  • Krankenhaus Barmherzige Schwestern Linz
  • Salzburger Landeskliniken
Principal Investigator: Stephan Polterauer, MD Medical University of Vienna
Study Director: Stephan Polterauer, MD Medical University of Vienna
Medical University of Vienna
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP