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

NCT06390904 | Active Not Recruiting Phase 2

• 1 other identifier: 53211030-3
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Atypical Endometrial Hyperplasia; Progesterone Resistance; Obesity

Outcome Measures

Primary Outcomes (1)

• Complete response (CR) rate within 28 weeks of treatment

  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.

  Up to 28 weeks

Secondary Outcomes (4)

• Adverse events

  During the treatment period, an average of 28 weeks

• 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

Study Arms (1)

Obese EAH group

EXPERIMENTAL

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.

Drug: GnRH antagonist; Drug: Letrozole 2.5mg

Interventions

GnRH antagonist 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.

Obese EAH group

Letrozole 2.5mg DRUG

2.5mg po qd.

Obese EAH group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Xiaojun Chen: lead

Study Sites (2)

Tenth People's Hospital of Tongji University

Shanghai, Shanghai Municipality, China

Location

Obstetrics and Gynecology Hospital, Fudan University

Shanghai, China

Location

Related Publications (1)

• 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.

  PMID: 34085795 BACKGROUND

MeSH Terms

Conditions

Endometrial Hyperplasia; Progesterone Resistance; Obesity

Interventions

LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)-; Letrozole

Condition Hierarchy (Ancestors)

Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 22, 2024
• First Posted: April 30, 2024
• Study Start: July 13, 2022
• Primary Completion: July 30, 2025
• Study Completion (Estimated): July 30, 2027
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)