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

April 25, 2024 updated by: Xiaojun Chen

Gonadotropin-releasing Hormone Agonist (GnRHa) Plus Letrozole in Obese Progestin-insensitive Endometrial Atypical Hyperplasia Patients With Conservative Treatment

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

29

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China
        • Recruiting
        • Obstetrics and Gynecology Hospital, Fudan University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.
Drug: Letrozole 2.5mg
2.5mg po qd.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response (CR) rate within 28 weeks of treatment
Time Frame: 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.
Up to 28 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: During the treatment period, an average of 28 weeks
Adverse effects were recorded during the entire treatment period, including weight gain, thrombosis, lactic acidosis, abnormal liver and renal function, and other toxicities or complaints.
During the treatment period, an average of 28 weeks
Time to achieve CR
Time Frame: During the treatment period, an average of 28 weeks
The median CR time will be calculated.
During the treatment period, an average of 28 weeks
Relapse rate
Time Frame: Average of 2 years after the completion of the treatment
Relapse will be defined as endometrial hyperplasia or endometrial cancer recurred after patients achieve CR.
Average of 2 years after the completion of the treatment
Rate of fertility outcomes
Time Frame: Average of 2 years after the completion of the treatment
Among patients prepared to get pregnant, fertility outcomes will be recorded.
Average of 2 years after the completion of the treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xiaojun Chen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 13, 2022

Primary Completion (Estimated)

June 30, 2025

Study Completion (Estimated)

June 30, 2025

Study Registration Dates

First Submitted

April 22, 2024

First Submitted That Met QC Criteria

April 25, 2024

First Posted (Actual)

April 30, 2024

Study Record Updates

Last Update Posted (Actual)

April 30, 2024

Last Update Submitted That Met QC Criteria

April 25, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 53211030-3

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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