Topical Imiquimod Versus Conization to Treat Cervical Intraepithelial Neoplasia

Brief Title

Topical Imiquimod Versus Conization to Treat Cervical Intraepithelial Neoplasia

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 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 Phase

Phase 3

Study Type

Interventional

Primary Outcome

HPV clearance

Secondary Outcome

 Rates of CIN remission/regression and/or CIN persistence/regression after treatment

Condition

Cervical Intraepithelial Neoplasia

Intervention

Topical Imiquimod

Study Arms / Comparison Groups

 Topical Imiquimod

Description:  16 weeks topical Imiquimod

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

95

Start Date

May 2013

Completion Date

January 2018

Primary Completion Date

September 2017

Eligibility Criteria

        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
      

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Stephan Polterauer, MD, , 

Location Countries

Austria

Location Countries

Austria

NCT ID

NCT01283763

Organization ID

ITIC2

Responsible Party

Principal Investigator

Study Sponsor

Medical University of Vienna

Collaborators

 Medical University of Graz

Study Sponsor

Stephan Polterauer, MD, Principal Investigator, Medical University of Vienna

Verification Date

October 2016