Atypical Endometrial HyperplasiaPhase 2/3NCT06390904
GnRHa + Letrozole in Obese Progestin-insensitive Endometrial Atypical Hyperplasia Patients
A Phase 2/3 study testing GnRH antagonist and Letrozole 2.5mg in people with Atypical Endometrial Hyperplasia and Progesterone Resistance, run by Xiaojun Chen at 2 sites in China.
Trial summary
To investigate the efficacy of Gonadotropin-releasing Hormone Agonist (GnRHa) plus letrozole in obese progestin-insensitive atypical endometrial hyperplasia (EAH) patients. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Atypical Endometrial Hyperplasia, Progesterone Resistance, Obesity
- What is being tested?
- GnRH antagonist and Letrozole 2.5mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesChina
- Study dates
- 13 Jul 2022to 30 Jul 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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)
Trial locations and contacts
2 sites in 1 country.
China2 sites
Tenth People's Hospital of Tongji University
Shanghai, Shanghai Municipality
Obstetrics and Gynecology Hospital, Fudan University
Shanghai
About this study
Official title: 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.
Read the 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.
- Being tested
- GnRH antagonist, Letrozole 2.5mg
- Medical subject headings
- Endometrial Hyperplasia, Progesterone Resistance, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GnRH antagonistDrug
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.
Letrozole 2.5mgDrug
2.5mg po qd.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: GnRH antagonist; Drug: Letrozole 2.5mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 28 weeks
Secondary outcomes (4)
Adverse events
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.
Measured: During the treatment period, an average of 28 weeks
Time to achieve CR
The median CR time will be calculated.
Measured: During the treatment period, an average of 28 weeks
Relapse rate
Relapse will be defined as endometrial hyperplasia or endometrial cancer recurred after patients achieve CR.
Measured: Average of 2 years after the completion of the treatment
Rate of fertility outcomes
Among patients prepared to get pregnant, fertility outcomes will be recorded.
Measured: Average of 2 years after the completion of the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2024
- Study start13 Jul 2022
- Primary completion30 Jul 2025
- Study completion30 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atypical Endometrial HyperplasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xiaojun Chen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Xiaojun Chen, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06390904
- Sponsor's protocol ID
- 53211030-3
- Status last verified
- Aug 2025
- First submitted
- 22 Apr 2024
- Last updated
- 11 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34085795
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gonadotropin-releasing Hormone Agonist (GnRHa) Plus Letrozole in Obese Progestin-insensitive Endometrial Atypical Hyperplasia Patients With Conservative Treatment
- ClinicalTrials.gov ID
- NCT06390904
- Acronym / sponsor ID
- 53211030-3
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- Xiaojun ChenUniversity, hospital or other
- Study start
- 13 Jul 2022 (actual)
- Primary completion
- 30 Jul 2025 (actual)
- Study completion
- 30 Jul 2027 (estimated)
- First posted
- 30 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To investigate the efficacy of Gonadotropin-releasing Hormone Agonist (GnRHa) plus letrozole in obese progestin-insensitive atypical endometrial hyperplasia (EAH) patients.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Obese EAH group | Experimental | Drug: GnRH antagonist, Drug: Letrozole 2.5mgThis 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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:
- Progestin-insensitive:
- Have a desire for remaining reproductive function or uterus
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GnRH antagonistGonadotropin-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 | Obese EAH group |
| Letrozole 2.5mg2.5mg po qd. | Drug | Obese EAH group |
Primary outcome
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.
4 secondary outcomes
Adverse events
Time frame: During the treatment period, an average of 28 weeks
Time to achieve CR
Time frame: During the treatment period, an average of 28 weeks
Relapse rate
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2025.
- Background: PubMed 34085795Zhou 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing GnRH antagonist and Letrozole 2.5mg in people with Atypical Endometrial Hyperplasia and Progesterone Resistance, run by Xiaojun Chen at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response (CR) rate within 28 weeks of treatment (time frame: Up to 28 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06390904, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2025.