Clinical trial NCT06390904: GnRHa + Letrozole in Obese Progestin-insensitive Endometrial Atypical Hyperplasia Patients
Official title: Gonadotropin-releasing Hormone Agonist (GnRHa) Plus Letrozole in Obese Progestin-insensitive Endometrial Atypical Hyperplasia Patients With Conservative Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Atypical Endometrial Hyperplasia
Progesterone Resistance
Obesity
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2024-04-30
Enrollment: 29
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To investigate the efficacy of Gonadotropin-releasing Hormone Agonist (GnRHa) plus letrozole in obese progestin-insensitive atypical endometrial hyperplasia (EAH) 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 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.

Eligibility criteria: Inclusion Criteria:

* 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:

  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)

Primary outcomes:
measure: Complete response (CR) rate within 28 weeks of treatment
timeFrame: Up to 28 weeks
Secondary outcomes:
measure: Adverse events
timeFrame: During the treatment period, an average of 28 weeks
measure: Time to achieve CR
timeFrame: During the treatment period, an average of 28 weeks
measure: Relapse rate
timeFrame: Average of 2 years after the completion of the treatment
measure: Rate of fertility outcomes
timeFrame: Average of 2 years after the completion of the treatment
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Tenth People's Hospital of Tongji University
state: Shanghai
city: Shanghai
country: China
facility: Obstetrics and Gynecology Hospital, Fudan University
Study officials:
References:
citation: Zhou S, Xu Z, Yang B, Guan J, Shan W, Shi Y, Chen X. Characteristics of progestin-insensitive early stage endometrial cancer and atypical hyperplasia patients receiving second-line fertility-sparing treatment. J Gynecol Oncol. 2021 Jul;32(4):e57. doi: 10.3802/jgo.2021.32.e57.