GnRHa + Letrozole in Non-obese Progestin-insensitive Endometrial Cancer and Atypical Hyperplasia Patients

April 22, 2024 updated by: Xiaojun Chen

Gonadotropin-releasing Hormone Agonist (GnRHa) Plus Letrozole in Non-obese Progestin-insensitive Early-stage Endometrial Cancer and Atypical Hyperplasia Patients With Conservative Treatment

To investigate the efficacy of GnRHa plus letrozole vs Diane-35 plus metformin in non-obese progestin-insensitive early-stage endometrial cancer (EEC) and atypical hyperplasia(EAH) patients asking for conservative treatment.

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 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 GnRHa plus letrozole or ethinylestradiol cyproterone plus metformin could be a better second-line treatment for progestin-insensitive patients. Till now, no similar studies were found, so we design this study to explore the efficacy of GnRHa plus letrozole and ethinylestradiol cyproterone plus metformin in progestin-insensitive EEC and EAH patients to provide new evidences for improving conservative treatment efficacy. Considered there will be more thrombotic risks in obese patients using ethinylestradiol cyproterone, we enrolled patients with BMI < 30kg/m2 only in this study.

This will be a single-centred prospective pilot study. Patients diagnosed as progestin-insensitive EAH or EEC by dilatation and curettage (D&C) or hysteroscopy will be enrolled. Non-obese patients will be stratified by pathological diagnosis (EEC or EAH) and then they will be randomly assigned (1:1) to two arms. One will be GnRHa + letrozole group and another will be ethinylestradiol cyproterone + metformin group.

The primary endpoint is cumulative complete response (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)

80

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 Contact

  • Name: Xiaojun Chen, PhD
  • Phone Number: 6429 8602133189900
  • Email: cxjlhjj@163.com

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200011
        • Recruiting
        • Obstetrics and Gynecology Hospital, Fudan University
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Bingyi Yang
        • Sub-Investigator:
          • Pengfei Wu
        • Principal Investigator:
          • Xiaojun Chen

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

No

Description

Inclusion Criteria:

  • Have a confirmed initial pathological diagnosis based upon hysteroscopy: histologically prove EAH or well-differentiated EEC G1 without myometrial invasion
  • BMI<30kg/m2
  • No signs of suspicious extrauterine involvement on enhanced magnetic resonance imaging (MRI) or enhanced computed tomography (CT) or ultrasound

  • 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 Diane-35, GnRHa, Letrozole or MET
  • 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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Non-obese EEC group (G)
20 non-obese EEC patients will be randomized to GnRHa + Letrozole group.Then every 12 weeks, an hysteroscope will be used to evaluate the endometrial condition, and the pathological findings will be recorded.
Drug: GnRHa
Gonadotropin-releasing hormone analogue, intramuscular injection of 3.75mg will be given every 4 weeks , and the maximum using courses will be 6.
Other Names:
  • Triprorelin acetate
Drug: Letrozole 2.5mg
2.5mg po qd and no more than 24 weeks
Experimental: Non-obese EEC group (D)
20 non-obese EEC patients will be randomized to Diane-35 + metformin group.Then every 12 weeks, an hysteroscope will be used to evaluate the endometrial condition, and the pathological findings will be recorded.
Drug: Diane-35
Periodic use. Patients will receive one pill po qd for 21 days, and next period should be started after 7 days.
Other Names:
  • ethinylestradiol cyproterone
Drug: MET
500mg po tid
Experimental: Non-obese EAH group (G)
20 non-obese EAH patients will be randomized to GnRHa + Letrozole group.Then every 12 weeks, an hysteroscope will be used to evaluate the endometrial condition, and the pathological findings will be recorded.
Drug: GnRHa
Gonadotropin-releasing hormone analogue, intramuscular injection of 3.75mg will be given every 4 weeks , and the maximum using courses will be 6.
Other Names:
  • Triprorelin acetate
Drug: Letrozole 2.5mg
2.5mg po qd and no more than 24 weeks
Experimental: Non-obese EAH group (D)
20 non-obese EAH patients will be randomized to Diane-35 + metformin group.Then every 12 weeks, an hysteroscope will be used to evaluate the endometrial condition, and the pathological findings will be recorded.
Drug: Diane-35
Periodic use. Patients will receive one pill po qd for 21 days, and next period should be started after 7 days.
Other Names:
  • ethinylestradiol cyproterone
Drug: MET
500mg po tid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response rates within 28 weeks of treatment
Time Frame: From date of randomization until the date of CR, assessed up to 28 weeks
The cumulative 28-week CR rates will be calculated in two groups. Patients will be evaluated with an hysteroscopy every 12 weeks. For some may delay the evaluation as personal reasons, we define the primary outcome measure as complete response rates within 28 weeks of treatment.
From date of randomization until the date of CR, assessed up to 28 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: From date of randomization until the date of CR or date of hysterectomy, assessed up to 28 weeks
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 randomization until the date of CR or date of hysterectomy, assessed up to 28 weeks
Time to achieve complete response
Time Frame: From date of randomization until the date of CR or date of hysterectomy, assessed up to 28 weeks.
The median CR time will be calculated in two groups
From date of randomization until the date of CR or date of hysterectomy, assessed up to 28 weeks.
Relapse rates
Time Frame: Up to 2 years after the treatment
Up to 2 years after the treatment
Rates of fertility outcomes
Time Frame: Up to 2 years after the treatment
Including pregnancy and live-birth rates
Up to 2 years after the treatment
Compliance
Time Frame: Data on treatment and hysteroscopy management will be collected, and deviations from study protocol will be recorded in writing. For example, the time of drug interruptions due to related toxicities or AEs, and delay of hysteroscopy for personal reasons.
Data on treatment and hysteroscopy management will be collected, and deviations from study protocol will be recorded in writing. For example, the time of drug interruptions due to related toxicities or AEs, and delay of hysteroscopy for personal reasons.

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

Helpful Links

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)

March 30, 2025

Study Completion (Estimated)

March 30, 2025

Study Registration Dates

First Submitted

March 29, 2022

First Submitted That Met QC Criteria

April 6, 2022

First Posted (Actual)

April 7, 2022

Study Record Updates

Last Update Posted (Actual)

April 23, 2024

Last Update Submitted That Met QC Criteria

April 22, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 53211030

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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