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

NCT ID: NCT05316935

Last Updated: 2025-08-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-13

Study Completion Date

2027-03-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Endometrial Neoplasms Atypical Endometrial Hyperplasia Progesterone Resistance

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

GnRHa

Intervention Type DRUG

Gonadotropin-releasing hormone analogue, intramuscular injection of 3.75mg will be given every 4 weeks , and the maximum using courses will be 6.

Letrozole 2.5mg

Intervention Type DRUG

2.5mg po qd and no more than 24 weeks

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.

Group Type EXPERIMENTAL

Diane-35

Intervention Type DRUG

Periodic use. Patients will receive one pill po qd for 21 days, and next period should be started after 7 days.

MET

Intervention Type DRUG

500mg po tid

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.

Group Type EXPERIMENTAL

GnRHa

Intervention Type DRUG

Gonadotropin-releasing hormone analogue, intramuscular injection of 3.75mg will be given every 4 weeks , and the maximum using courses will be 6.

Letrozole 2.5mg

Intervention Type DRUG

2.5mg po qd and no more than 24 weeks

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.

Group Type EXPERIMENTAL

Diane-35

Intervention Type DRUG

Periodic use. Patients will receive one pill po qd for 21 days, and next period should be started after 7 days.

MET

Intervention Type DRUG

500mg po tid

Interventions

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GnRHa

Gonadotropin-releasing hormone analogue, intramuscular injection of 3.75mg will be given every 4 weeks , and the maximum using courses will be 6.

Intervention Type DRUG

Letrozole 2.5mg

2.5mg po qd and no more than 24 weeks

Intervention Type DRUG

Diane-35

Periodic use. Patients will receive one pill po qd for 21 days, and next period should be started after 7 days.

Intervention Type DRUG

MET

500mg po tid

Intervention Type DRUG

Other Intervention Names

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Triprorelin acetate ethinylestradiol cyproterone

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Xiaojun Chen

OTHER

Sponsor Role lead

Responsible Party

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Xiaojun Chen

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Obstetrics and Gynecology Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Tenth People's Hospital of Tongji University

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Xiaojun Chen, PhD

Role: CONTACT

8602133189900 ext. 6429

Bingyi Yang

Role: CONTACT

8602133189900 ext. 6429

Facility Contacts

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Xiaojun Chen, PhD

Role: primary

862133189900 ext. 6429

Bingyi Yang, MD

Role: backup

862133189900 ext. 6429

Weina Wang

Role: primary

8602166300588

References

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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)

Related Links

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Other Identifiers

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53211030

Identifier Type: -

Identifier Source: org_study_id

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