Atypical Endometrial Hyperplasia, Endometrial Neoplasms, Obesity, Progesterone Resistance
Conditions
Brief summary
To investigate the efficacy of GnRHa plus letrozole in obese progestin-insensitive EEC patients.
Detailed description
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 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 GnRHa plus letrozole could be a better second-line treatment for obese progestin-insensitive patients. Till now, no similar studies were found, so we design this study to explore the efficacy of GnRHa plus letrozole in obese progestin-insensitive EEC and EAH patients to provide new evidences for improving conservative treatment efficacy. We defined obese patients as these with BMI ≥ 30kg/m2. This will be a single-centred prospective pilot study. Patients diagnosed as obese progestin-insensitive EEC by dilatation and curettage (D&C) or hysteroscopy will be enrolled. The primary endpoint is cumulative complete response (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.
Interventions
DRUGGnRH antagonist
Gonadotropin-releasing hormone analogue, intramuscular injection of 3.75mg will be given every 4 weeks, and the maximum treatment courses will be 6. If the patient get CR within 6 courses, another 2 courses will be used as consolidation therapy.
DRUGLetrozole 2.5mg
2.5mg po qd.
Sponsors
Xiaojun Chen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Have a confirmed initial pathological diagnosis based upon hysteroscopy: histologically prove well-differentiated EEC G1 without myometrial invasion * BMI≥30kg/m2 * No signs of suspicious extrauterine involvement on enhanced magnetic resonance imaging (MRI) or enhanced computed tomography (CT) or ultrasound * Using progestin, any of the following therapy, as first-line treatment: 1. Megestrol acetate ≥ 160 mg qd using, combined with Levonorgestrel Lntrauterine System (LNG-IUS) inserted or not 2. Medroxyprogesterone acetate ≥ 250 mg qd using, combined with LNG-IUS inserted or not 3. LNG-IUS inserted * Progestin-insensitive: 1. remained with stable disease after 7 months of progestin use 2. 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
Exclusion criteria
* 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rates within 28 weeks of treatment | Up to 28 weeks | The cumulative 28-week CR rates will be calculated in two groups. Patients will be evaluated with an hysteroscopy every 12 to 16 weeks. For some may delay the evaluation as personal reasons, we define the primary outcome measure as complete response rates within 28 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Through study completion, an average of 28 weeks | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be recorded, as well as incidence of adverse events. |
| Time to achieve complete response | Up to 28 weeks | The median CR time will be calculated. |
| Relapse rates | Through study completion, an average of 2 years | — |
| Rates of fertility outcomes | Through study completion, an average of 2 years | — |
| Compliance | Through study completion, an average of 28 weeks | Data on treatment and hysteroscopy management will be collected, and deviations from study protocol will be recorded in writing. For example, the time of drug interruptions due to related toxicities or AEs, and delay of hysteroscopy for personal reasons. |
Countries
China
Contacts
CONTACTXiaojun Chen, PhD
CONTACTPengfei Wu
Outcome results
None listed