Gonadotropin-releasing Hormone Agonist (GnRHa) Plus Letrozole in Obese Progestin-insensitive Endometrial Atypical Hyperplasia Patients With Conservative Treatment
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 29
- 试验地点
- 2
- 主要终点
- Complete response (CR) rate within 28 weeks of treatment
研究概览
简要总结
To investigate the efficacy of Gonadotropin-releasing Hormone Agonist (GnRHa) plus letrozole in obese progestin-insensitive atypical endometrial hyperplasia (EAH) patients.
详细描述
There were more and more women with early endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (EAH) who want to preserve fertility.
Approximately 70% to 80% of females who meet the criteria for conservation treatment are able to achieve complete response (CR) after progestin therapy, with a median time of 6-7 months, but about 20% to 30% of patients get no response or need to take longer time to achieve remission (over one year). With long duration of treatment, there will be more side effects such as weight gain, impaired liver function, endometrial injury, ovarian reserve inhibition etc. which will decrease the efficacy of conservative treatment. Previous researches had shown that Gonadotropin-releasing Hormone Agonist (GnRHa) plus letrozole could be a better second-line treatment for obese progestin-insensitive patients. Till now, no similar studies were found, so the investigators design this study to explore the efficacy of GnRHa plus letrozole in obese progestin-insensitive EAH patients to provide new evidences for improving conservative treatment efficacy. The investigators defined obese patients as these with BMI ≥ 30kg/m^2.
This will be a single-centred prospective pilot study. Patients diagnosed as obese progestin-insensitive EAH by dilatation and curettage (D&C) or hysteroscopy will be enrolled. The primary endpoint is cumulative CR rate at 28 weeks of treatment. The secondary endpoints include adverse events, duration of complete response, recurrent rate, pregnancy rate and quality of life of patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Have a confirmed initial pathological diagnosis based upon hysteroscopy: histologically prove EAH
- •BMI≥30kg/m2
- •Using progestin, any of the following therapy, as first-line treatment:
- •Megestrol acetate ≥ 160 mg qd using, combined with Levonorgestrel Lntrauterine System (LNG-IUS) inserted or not
- •Medroxyprogesterone acetate ≥ 250 mg qd using, combined with LNG-IUS inserted or not
- •LNG-IUS inserted
- •Progestin-insensitive:
- •remained with stable disease after 7 months of progestin use
- •did not achieve CR after 10 months of progestin use
- •Have a desire for remaining reproductive function or uterus
- •Good compliance with adjunctive treatment and follow-up
排除标准
- •Combined with severe medical disease or severely impaired liver and kidney function
- •Pathologically confirmed as endometrial cancer with suspicious myometrial invasion or extrauterine metastasis
- •Patients with other types of endometrial cancer or other malignant tumors of the reproductive system
- •Patients with breast cancer or other hormone- dependent tumors or diseases that cannot be used with GnRHa or Letrozole
- •Strong request for uterine removal or other conservative treatment
- •Known or suspected pregnancy
- •Acute severe disease such as stroke or heart infarction or a history of thrombosis disease
- •Smoker(>15 cigarettes a day)
研究组 & 干预措施
Obese EAH group
This group including 29 EAH cases. Interventional Study Model was Simon two-stage optimal design. Eleven patients were needed for the first stage, and if eight or more patients achieved CR at 28 weeks, the trial can enter into the second stage.
Then every 12 to 16 weeks, an hysteroscope will be used to evaluate the endometrial condition, and the pathological findings will be recorded.
干预措施: GnRH antagonist (Drug)
Obese EAH group
This group including 29 EAH cases. Interventional Study Model was Simon two-stage optimal design. Eleven patients were needed for the first stage, and if eight or more patients achieved CR at 28 weeks, the trial can enter into the second stage.
Then every 12 to 16 weeks, an hysteroscope will be used to evaluate the endometrial condition, and the pathological findings will be recorded.
干预措施: Letrozole 2.5mg (Drug)
结局指标
主要结局
Complete response (CR) rate within 28 weeks of treatment
时间窗: Up to 28 weeks
The cumulative 28-week CR rate will be calculated. Patients will be evaluated with an hysteroscopy every 12 to 16 weeks. The response to progestin treatment was assessed histologically using specimens obtained during each hysteroscopic evaluation. CR was defined as the absence of hyperplasia or carcinoma.
次要结局
- Time to achieve CR(During the treatment period, an average of 28 weeks)
- Relapse rate(Average of 2 years after the completion of the treatment)
- Rate of fertility outcomes(Average of 2 years after the completion of the treatment)
- Adverse events(During the treatment period, an average of 28 weeks)
研究者
Xiaojun Chen
Professor
Fudan University