Gonadotropin-releasing Hormone Agonist (GnRHa) Plus Letrozole In Young Women With Early Endometrial Cancer

March 26, 2023 updated by: Xiaojun Chen, Fudan University

Gonadotropin-releasing Hormone Agonist Combined With Letrozole Compared With Megestrol Acetate or Medroxyprogesterone Acetate Alone as Fertility-sparing Treatment in Early Endometrial Cancer

To see if Gonadotropin-releasing hormone analogue (GnRHa) combined with aromatase inhibitors (AIs) will achieve better complete response rate than megestrol acetate or medroxyprogesterone acetate (MA/MPA) alone as fertility-sparing treatment for patients with early endometrial carcinoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This will be a multicenter randomized controlled study to evaluate the treatment effects and adverse events of GnRHa plus AIs compared with MA/MPA in primary EEC patients.In this study, young patients (18-45 years) diagnosed as EEC for the first time seeking for fertility preserving treatment at the Obstetrics and Gynecology Hospital of Fudan University were screened. Patients were randomly assigned (1:1) to GnRHa+letrozole group (triprorelin acetate, intramuscular injection of 3.75mg was given 4 weeks apart and the maximum use are 6 courses. letrozole, 2.5mg oral daily and no more than 24 weeks) or MA/MPA group (160 mg oral MA daily or 500 mg oral MPA daily).

Hysteroscopy will be performed every 3 months during treatment to evaluate the treatment effects. For patients with EEC, complete response (CR) is defined as the reversion of endometrial carcinoma to proliferative or secretory endometrium; partial response (PR) is defined as regression to simple or complex hyperplasia with or without atypia; Stable disease (SD) is defined as the persistence of the disease; and progressive disease (PD) is defined as the progression of endometrial lesions. Continuous therapies will be needed in PR, SD or PD.The primary endpoint was cumulative complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were cumulative CR rate at 28weeks of treatment, adverse events, recurrent rate, pregnancy rate, effects on ovarian function and quality of life of patients.

Study Type

Interventional

Enrollment (Anticipated)

104

Phase

  • Phase 2

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
      • Shanghai, Shanghai, China, China, 200011
        • Recruiting
        • Obstetrics and Gynecology Hospital, Fudan University

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

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Consent informed and signed
  • Primarily have a confirmed diagnosis of early-stage endometrial cancer (endometrioid, grade I, without myometrial inva- sion) ) based upon endometrial biopsy, diagnostic curettage or hysteroscopy
  • No signs of suspicious myometrial invasion or extrauterine metastasis by enhanced magnetic resonance imaging (MRI), enhanced computed tomography (CT) or transvaginal ultrasonography (TVUS)
  • Have a strong desire for remaining reproductive function or uterus
  • Have good compliance and follow-up conditions, and patients are willing to follow up in Obstetrics and Gynecology Hospital of Fudan University in time

Exclusion Criteria:

  • Pathologically confirmed as endometrial cancer with suspicious myometrial invasion or extrauterine metastasis
  • Recurrent endometrial cancer
  • Combined with severe medical disease or severely impaired liver and kidney function
  • Patients with other types of endometrial cancer or other malignant tumors of the reproductive system; patients with breast cancer or other hormone- dependent tumors that cannot be used with progesterone
  • Those who require hysterectomy or other methods other than conservative treatment with drugs
  • Known or suspected pregnancy
  • Contraindication for Medroxyprogesterone Acetate, Megestrol Acetate, Triprorelin Acetate, Letrozole or pregnancy
  • Hormone treatment within 3 months before entering the trial;
  • 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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GnRHa+letrozole
Patients will be stratified into BMI≥28kg/m2 group and BMI<28kg/m2 group. Patients in BMI≥28kg/m2 or BMI<28kg/m2 group will be randomly assigned (1:1) to GnRHa+letrozole group or MA/MPA group. Patients who will be assigned to GnRHa+letrozole group will receive triprorelin acetate (intramuscular injection of 3.75mg was given 4 weeks apart and the maximum use are 6 courses) plus letrozole (2.5mg oral daily and no more than 24 weeks). Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded.
Drug: Triprorelin Acetate
Intramuscular injection of 3.75mg was given 4 weeks apart and the maximum use are 6 courses
Drug: Letrozole 2.5mg
At a dosage of 2.5mg/day and no more than 24 weeks
Other Names:
  • Letrozole
Active Comparator: MA/MPA
Patients will be stratified into BMI≥28kg/m2 group and BMI<28kg/m2 group. Patients in BMI≥28kg/m2 or BMI<28kg/m2 group were randomly assigned (1:1) to GnRHa+letrozole group or MA/MPA group.Patients assigned to MA/MPA group will receive MA/MPA (160 mg oral MA daily or 500 mg oral MPA daily).Then every 3 months, an hysteroscopy will be used to evaluate the endometrial condition, and the findings will be recorded.
Drug: Megestrol Acetate 160 MG Oral Tablet
At a dosage of 160 mg/day
Other Names:
  • Megestrol Acetate
Drug: Medroxyprogesterone Acetate 500 MG
At a dosage of 500 mg/day
Other Names:
  • Medroxyprogesterone Acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response rates within 16 weeks of treatment
Time Frame: From date of treatment initiation until the date of CR, assessed up to 16 weeks.
The cumulative 16-week CR rates will be calculated in two groups
From date of treatment initiation until the date of CR, assessed up to 16 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response rates within 28 weeks of treatment
Time Frame: From date of treatment initiation until the date of CR, assessed up to 28 weeks.
The cumulative 28-week CR rates will be calculated in two groups
From date of treatment initiation until the date of CR, assessed up to 28 weeks.
Time to achieve complete response
Time Frame: From date of treatment initiation until the date of CR or date of hysterectomy,From date of randomization until the date of CR, assessed up to 2 years
The median CR time will be calculated in two groups
From date of treatment initiation until the date of CR or date of hysterectomy,From date of randomization until the date of CR, assessed up to 2 years
Adverse events
Time Frame: From date of treatment initiation until the date of CR, assessed up to 2 years
Adverse events related with Medroxyprogesterone Acetate, Megestrol Acetate, Triprorelin Acetate and Letrozole. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be recorded, as well as incidence of adverse events.
From date of treatment initiation until the date of CR, assessed up to 2 years
Quality of life during the treatment accessed by WHOQOL-BREF
Time Frame: From date of randomization until 12 weeks after treatment is over.
Quality of life will be assessed at baseline, 4 weeks and every 12-16 weeks of treatment, using WHOQOL-BREF scale including assessment on pain, energy,sleep,mobil,activity,medication,work,positive feeling,think,esteem,body,negtivity,spirit,relationship,support,sex,safety,home,finance,service,information, environment,leisure,transport
From date of randomization until 12 weeks after treatment is over.
Relapse rates
Time Frame: up to 2 years after the treatment for each patient
All enrolled patients will be followed up for 2 years. During the following-up period, if patients recur after complete response, they will be counted and the number of recurrence will be divided by number of patients followed up, then we can get the relapse rates. Comparison will be performed between two groups.
up to 2 years after the treatment for each patient
Change of AMH (anti-mullerian hormone ) serum level
Time Frame: From date of randomization until 24 weeks after treatment is over.
AMH (anti-mullerian hormone ) will be assessed at baseline and every 12-16 weeks.
From date of randomization until 24 weeks after treatment is over.
The rates of fertility outcomes
Time Frame: up to 2 years after the treatment for each patient
The percentage of pregnancy and live-birth will be counted.
up to 2 years after the treatment for each patient

Collaborators and Investigators

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

Sponsor

Fudan University

Collaborators

Peking Union Medical College Hospital

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)

March 11, 2022

Primary Completion (Anticipated)

March 10, 2024

Study Completion (Anticipated)

March 10, 2025

Study Registration Dates

First Submitted

January 16, 2022

First Submitted That Met QC Criteria

February 15, 2022

First Posted (Actual)

February 18, 2022

Study Record Updates

Last Update Posted (Actual)

March 28, 2023

Last Update Submitted That Met QC Criteria

March 26, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 53211032

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be shared after this research being published,without patients personal information.

IPD Sharing Time Frame

Data will be avaliable since this research being published

IPD Sharing Access Criteria

Institutes or researchers who require the data should contact the principle investigator Prof.Xiaojun Chen via email that after this study being published.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

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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