TOPical Imiquimod Treatment of High-grade Cervical Intraepithelial Neoplasia, a Multicenter, Open-label, Non-randomized, Controlled Study (TOPIC-3 Study)
试验速览
- 阶段
- 不适用
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- Identification of predictive biomarkers for treatment efficacy of imiquimod in the individual patient.
研究概览
简要总结
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.
详细描述
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 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.
A control colposcopy will be performed after 10 weeks for the imiquimod group. In case of progressive disease, the treatment will be ended and LLETZ will be performed as treatment. For patients in which the treatment is continued, treatment efficacy will be evaluated after 20 weeks, by colposcopy with diagnostic biopsies. Statistical analysis will be performed based on an intention-to-treat analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •de novo CIN2 or CIN3 lesion, histologically confirmed by diagnostic biopsy
- •age of 18 years or older
排除标准
- •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
研究组 & 干预措施
Imiquimod treatment arm
Treatment by vaginal imiquimod cream during 16 weeks.
干预措施: Imiquimod (Drug)
Standard treatment arm
Treatment by large loop excision of the transformation zone.
干预措施: Large Loop Excision of the Transformation Zone (Procedure)
结局指标
主要结局
Identification of predictive biomarkers for treatment efficacy of imiquimod in the individual patient.
时间窗: Baseline (T=0)
Histological biomarkers will be identified in the cervical biopsies performed at baseline.
Treatment efficacy of imiquimod 5% cream for the treatment of CIN2-3 lesions, compared to LLETZ treatment, in selected populations.
时间窗: 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.
次要结局
- Disease recurrence(6, 12 and 24 months)
- Side effects of imiquimod therapy and LLETZ therapy.(20 weeks)
- 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)