GnRHa + Letrozole in Obese Progestin-insensitive Endometrial Atypical Hyperplasia Patients

NCT ID: NCT06390904

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-13
• Study Completion Date: 2027-07-30

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.

Conditions

Atypical Endometrial Hyperplasia; Progesterone Resistance; Obesity

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

GnRH antagonist

Intervention Type: DRUG

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.

Letrozole 2.5mg

Intervention Type: DRUG

2.5mg po qd.

Interventions

GnRH 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.

Intervention Type: DRUG

Letrozole 2.5mg

2.5mg po qd.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Xiaojun Chen

OTHER

Sponsor Role: lead

Responsible Party

Xiaojun Chen

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Tenth People's Hospital of Tongji University

Shanghai, Shanghai Municipality, China

Obstetrics and Gynecology Hospital, Fudan University

Shanghai, , China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 34085795 (View on PubMed)

Other Identifiers

53211030-3

Identifier Type: -

Identifier Source: org_study_id