Endometrial NeoplasmsPhase 2/3NCT05316935
GnRHa + Letrozole in Non-obese Progestin-insensitive Endometrial Cancer and Atypical Hyperplasia Patients
A Phase 2/3 study testing GnRHa, Letrozole 2.5mg and Diane-35 in people with Endometrial Neoplasms and Atypical Endometrial Hyperplasia, run by Xiaojun Chen at 2 sites in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Endometrial Neoplasms, Atypical Endometrial Hyperplasia, Progesterone Resistance
- What is being tested?
- GnRHa, Letrozole 2.5mg and Diane-35
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 2 sitesChina
- Study dates
- 13 Jul 2022to 30 Mar 2028
- Phase
- Phase 2/3
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 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:
- 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
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- LNG-IUS inserted
- 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 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)
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Obstetrics and Gynecology Hospital, Fudan University
Shanghai, Shanghai Municipality, 200011
Xiaojun Chen, PhD, 862133189900 ext. 6429, cxjlhjj@163.com
Bingyi Yang, MD, 862133189900 ext. 6429, xiaomihaoku@163.com
- Recruiting
Tenth People's Hospital of Tongji University
Shanghai, Shanghai Municipality
Weina Wang, 8602166300588, wangweinals@163.com
About this study
Official title: 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.
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 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.
- Being tested
- GnRHa, Letrozole 2.5mg, Diane-35, MET
- Medical subject headings
- Endometrial Neoplasms, Endometrial Hyperplasia, Progesterone Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GnRHaDrug
Also called Triprorelin acetate
Gonadotropin-releasing hormone analogue, intramuscular injection of 3.75mg will be given every 4 weeks , and the maximum using courses will be 6.
Letrozole 2.5mgDrug
2.5mg po qd and no more than 24 weeks
Diane-35Drug
Also called ethinylestradiol cyproterone
Periodic use. Patients will receive one pill po qd for 21 days, and next period should be started after 7 days.
METDrug
500mg po tid
| Study group | Role | What they receive |
|---|---|---|
| Non-obese EEC group (G) | Experimental | 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. Receives: Drug: GnRHa; Drug: Letrozole 2.5mg |
| Non-obese EEC group (D) | Experimental | 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. Receives: Drug: Diane-35; Drug: MET |
| Non-obese EAH group (G) | Experimental | 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. Receives: Drug: GnRHa; Drug: Letrozole 2.5mg |
| Non-obese EAH group (D) | Experimental | 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. Receives: Drug: Diane-35; Drug: MET |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rates within 28 weeks of treatment
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.
Measured: From date of randomization until the date of CR, assessed up to 28 weeks
Secondary outcomes (5)
Adverse events
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be recorded, as well as incidence of adverse events.
Measured: From date of randomization until the date of CR or date of hysterectomy, assessed up to 28 weeks
Time to achieve complete response
The median CR time will be calculated in two groups
Measured: From date of randomization until the date of CR or date of hysterectomy, assessed up to 28 weeks.
Relapse rates
Measured: Up to 2 years after the treatment
Rates of fertility outcomes
Including pregnancy and live-birth rates
Measured: Up to 2 years after the treatment
Compliance
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2022
- Study start13 Jul 2022
- Primary completion30 Mar 2028 (estimated)
- Study completion30 Mar 2028 (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 Endometrial NeoplasmsStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 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
- NCT05316935
- Sponsor's protocol ID
- 53211030
- Status last verified
- Sep 2026
- First submitted
- 29 Mar 2022
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- 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