Clinical Trial: Imiquimod Treatment of High-grade CIN
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: TOPical Imiquimod Treatment of High-grade Cervical Intraepithelial Neoplasia, a Multicenter, Open-label, Non-randomized, Controlled Study (TOPIC-3 Study)
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:
- Imiquimod treatment arm(60 patients). Patients in this group are treated with vaginal imiquimod 5% cream during 16 weeks.
- Standard treatment arm (60 patients). Patients in this group will undergo LLETZ treatment.
Detailed Summary:
Cervical Intraepithelial Neoplasia (CIN) is the premalignant condition of cervical cancer. The standard treatment of histologically confirmed CIN2-3 is surgical excision by large loop excision of the transformation zone (LLETZ). This procedure has potential complications, such as hemorrhage, infection and preterm birth in subsequent pregnancies. For this reason, non-invasive therapies are needed. Imiquimod cream has been studied as a non-invasive treatment alternative in high-grade CIN, but evidence on treatment efficacy is limited and evidence on disease recurrence and quality of life during and after treatment is lacking. One RCT has been performed and shows that treatment of high-grade CIN with vaginal imiquimod cream leads to disease regression in 73%. Side-effects were generally mild, but common. A recent survey among gynecologists and a patient preference study indicate that imiquimod treatment of high-grade CIN is mainly preferred by a selected population of women with a future pregnancy wish. These women accept a lower treatment efficacy and higher rates of side-effects from imiquimod treatment in order to prevent future preterm birth caused by LLETZ treatment. Ideally, those women with a high probability of successful treatment would be selected.
The objective of this study is to investigate the treatment efficacy, side-effects and quality of life associated with imiquimod treatment of high-grade CIN lesions in a selected population of patients who prefer imiquimod treatment instead of LLETZ. The study also aims to identify predictive biomarkers clinical response to imiquimod treatment, in order to select patients in which good treatment response is expected.
The study design is a multicenter, open-label, non-randomized controlled intervention study. 120 women with a histological diagnosis of CIN2 or CIN3 will be
Sponsor: Maastricht University Medical Center
Current Primary Outcome:
- Treatment efficacy of imiquimod 5% cream for the treatment of CIN2-3 lesions, compared to LLETZ treatment, in selected populations. [ Time Frame: 6 months ]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.
- Identification of predictive biomarkers for treatment efficacy of imiquimod in the individual patient. [ Time Frame: Baseline (T=0) ]Histological biomarkers will be identified in the cervical biopsies performed at baseline.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Side effects of imiquimod therapy and LLETZ therapy. [ Time Frame: 20 weeks ]Scored by the Common Terminology Criteria for Adverse Events guidelines.
- Disease recurrence [ Time Frame: 6, 12 and 24 months ]Defined as abnormal cervical cytology for all treatment groups.
- General health-related Quality of life (QoL) before, during and after treatment [ Time Frame: Baseline, 20 weeks and 1 year ]Medical Outcomes Study 36-Item Short-Form General Health Survey (RAND 36)
- Cancer specific Quality of Life, during and after treatment [ Time Frame: Baseline, 20 weeks and 1 year ]European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire: QLQ-C30
- Cervical cancer specific Quality of life (QoL), during and after treatment [ Time Frame: Baseline, 20 weeks and 1 year ]European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire: QLQ-CX24
Original Secondary Outcome: Same as current
Information By: Maastricht University Medical Center
Dates:
Date Received: September 16, 2016
Date Started: November 2016
Date Completion: November 2020
Last Updated: November 7, 2016
Last Verified: September 2016
