Imiquimod Treatment of High-grade CIN

NCT02917746 | Unknown DMC

• 1 other identifier: NL 57849.068.16
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

Brief Summary

This multi-center, open-label, non-randomized controlled intervention study aims to investigate the treatment efficacy, side-effects and quality of life associated with imiquimod treatment of high-grade CIN lesions, as an alternative to surgical treatment by Large Loop Excision of the Transformation Zone (LLETZ). Non-surgical treatment may prevent side-effects associated with surgical treatment, such as premature birth in subsequent pregnancies. The study hypothesis is that approximately 75% of patients with high-grade CIN will be adequately treated with imiquimod. 120 women with a histological diagnosis of CIN2 or CIN3 will be included and allocated to one of two treatment arms according to their preference:

1. 1.Imiquimod treatment arm(60 patients). Patients in this group are treated with vaginal imiquimod 5% cream during 16 weeks.
2. 2.Standard treatment arm (60 patients). Patients in this group will undergo LLETZ treatment.

Conditions

Cervical Intraepithelial Neoplasia

Keywords

Cervical intraepithelial neoplasia; Imiquimod; Treatment; Predictive biomarkers

Outcome Measures

Primary Outcomes (2)

• Treatment efficacy of imiquimod 5% cream for the treatment of CIN2-3 lesions, compared to LLETZ treatment, in selected populations.

  Treatment efficacy for the imiquimod group is defined as regression to CIN 1 or less at 20 weeks follow-up. Treatment efficacy for the standard treatment group is defined as no need for additional treatment within 6 months after LLETZ treatment.

  6 months

• Identification of predictive biomarkers for treatment efficacy of imiquimod in the individual patient.

  Histological biomarkers will be identified in the cervical biopsies performed at baseline.

  Baseline (T=0)

Secondary Outcomes (5)

• Side effects of imiquimod therapy and LLETZ therapy.

  20 weeks

• Disease recurrence

  6, 12 and 24 months

• General health-related Quality of life (QoL) before, during and after treatment

  Baseline, 20 weeks and 1 year

• Cancer specific Quality of Life, during and after treatment

  Baseline, 20 weeks and 1 year

• Cervical cancer specific Quality of life (QoL), during and after treatment

  Baseline, 20 weeks and 1 year

Study Arms (2)

Imiquimod treatment arm

EXPERIMENTAL

Treatment by vaginal imiquimod cream during 16 weeks.

Drug: Imiquimod

Standard treatment arm

ACTIVE COMPARATOR

Treatment by large loop excision of the transformation zone.

Procedure: Large Loop Excision of the Transformation Zone

Interventions

Imiquimod DRUG

Patients in this group are treated with vaginal imiquimod cream during 16 weeks. A control colposcopy with diagnostic biopsies will be performed after 10 weeks to rule out disease progression. A final colposcopy with diagnostic biopsies will be performed after 20 weeks to evaluate disease efficacy.

Imiquimod treatment arm

Large Loop Excision of the Transformation Zone PROCEDURE

Patients in this group are treated with LLETZ.

Standard treatment arm

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• de novo CIN2 or CIN3 lesion, histologically confirmed by diagnostic biopsy
• age of 18 years or older

You may not qualify if:

• previous histologically confirmed high-grade CIN (CIN 2-3)
• concomitant vulvar and/or vaginal intraepithelial neoplasia
• previous cervical malignancy
• current malignant disease
• immunodeficiency (including HIV/AIDS and immunodepressive medication)
• pregnancy or lactation
• legal incapability

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Clinical Trial Center Maastricht B.V.: collaborator

Study Sites (3)

Meander Medical Center

Amersfoort, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6202AZ, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

Related Publications (7)

• Crane JM. Pregnancy outcome after loop electrosurgical excision procedure: a systematic review. Obstet Gynecol. 2003 Nov;102(5 Pt 1):1058-62. doi: 10.1016/s0029-7844(03)00741-5.

  PMID: 14672487 BACKGROUND

• Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet. 2006 Feb 11;367(9509):489-98. doi: 10.1016/S0140-6736(06)68181-6.

  PMID: 16473126 BACKGROUND

• Grimm C, Polterauer S, Natter C, Rahhal J, Hefler L, Tempfer CB, Heinze G, Stary G, Reinthaller A, Speiser P. Treatment of cervical intraepithelial neoplasia with topical imiquimod: a randomized controlled trial. Obstet Gynecol. 2012 Jul;120(1):152-9. doi: 10.1097/AOG.0b013e31825bc6e8.

  PMID: 22914404 BACKGROUND

• Pachman DR, Barton DL, Clayton AC, McGovern RM, Jefferies JA, Novotny PJ, Sloan JA, Loprinzi CL, Gostout BS. Randomized clinical trial of imiquimod: an adjunct to treating cervical dysplasia. Am J Obstet Gynecol. 2012 Jan;206(1):42.e1-7. doi: 10.1016/j.ajog.2011.06.105. Epub 2011 Jul 13.

  PMID: 21907959 BACKGROUND

• Lin CT, Qiu JT, Wang CJ, Chang SD, Tang YH, Wu PJ, Jung SM, Huang CC, Chou HH, Jao MS, Lai CH. Topical imiquimod treatment for human papillomavirus infection in patients with and without cervical/vaginal intraepithelial neoplasia. Taiwan J Obstet Gynecol. 2012 Dec;51(4):533-8. doi: 10.1016/j.tjog.2012.09.006.

  PMID: 23276555 BACKGROUND

• Koeneman MM, van de Sande AJ, van Beekhuizen HJ, Gerestein KG, van de Laar R, Kruitwagen RF, Kruse AJ. Physicians' Awareness, Attitudes, and Experiences Regarding Imiquimod Treatment of Vaginal and Cervical Intraepithelial Neoplasia. J Low Genit Tract Dis. 2016 Jan;20(1):75-9. doi: 10.1097/LGT.0000000000000158.

  PMID: 26579838 BACKGROUND

• Koeneman MM, Kruse AJ, Kooreman LF, Zur Hausen A, Hopman AH, Sep SJ, Van Gorp T, Slangen BF, van Beekhuizen HJ, van de Sande AJ, Gerestein CG, Nijman HW, Kruitwagen RF. Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial. BMC Cancer. 2017 Feb 7;17(1):110. doi: 10.1186/s12885-017-3108-9.

  PMID: 28173776 DERIVED

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Interventions

Imiquimod

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• A.J. Kruse, MD, PhD

  Maastricht University Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2016
• First Posted: September 28, 2016
• Study Start: November 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: December 1, 2020
• Last Updated: August 16, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3)