Topical Imiquimod Versus Conization to Treat Cervical Intraepithelial Neoplasia

NCT ID: NCT01283763

Last Updated: 2016-11-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2018-01-31

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.

Conditions

Cervical Intraepithelial Neoplasia

Keywords

Cervical Intraepithelial Neoplasia, Imiquimod, conization

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Topical Imiquimod

16 weeks topical Imiquimod

Group Type: EXPERIMENTAL

Topical Imiquimod

Intervention Type: DRUG

16 weeks

Conization

Large loop excision of the transformation zone

Group Type: ACTIVE_COMPARATOR

Conization

Intervention Type: PROCEDURE

Large loop excision of the transformation zone

Interventions

Topical Imiquimod

16 weeks

Intervention Type: DRUG

Conization

Large loop excision of the transformation zone

Intervention Type: PROCEDURE

Other Intervention Names

Aldara®

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Graz

OTHER

Sponsor Role: collaborator

Medical University Innsbruck

OTHER

Sponsor Role: collaborator

Krankenhaus Barmherzige Schwestern Linz

OTHER

Sponsor Role: collaborator

Salzburger Landeskliniken

OTHER

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Stephan Polterauer

Ass.Prof. MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephan Polterauer, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Stephan Polterauer, MD

Role: STUDY_DIRECTOR

Medical University of Vienna

Locations

Medical University of Vienna

Vienna, Austria, Austria

Countries

Austria

References

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.

Reference Type: DERIVED

PMID: 35177279 (View on PubMed)

Related Links

http://www.meduniwien.ac.at

Medical University of Vienna

Other Identifiers

ITIC2

Identifier Type: -

Identifier Source: org_study_id