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

Endometrial Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05316935
• Other study ID #: 53211030
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 13, 2022
• Est. completion date: March 30, 2025

Study information

• Verified date: April 2024
• Source: Fudan University
• Contact: Xiaojun Chen, PhD
• Phone: 8602133189900
• Email: cxjlhjj[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: March 30, 2025
• Est. primary completion date: March 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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)

Related Conditions & MeSH terms

• Atypical Endometrial Hyperplasia
• Endometrial Hyperplasia
• Endometrial Neoplasms
• Hyperplasia
• Progesterone Resistance

Intervention

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.
• Letrozole 2.5mg
2.5mg po qd and no more than 24 weeks
• Diane-35
Periodic use. Patients will receive one pill po qd for 21 days, and next period should be started after 7 days.
• MET
500mg po tid

Locations

Country	Name	City	State
China	Obstetrics and Gynecology Hospital, Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Xiaojun Chen

Country where clinical trial is conducted

China, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From date of randomization until the date of CR, assessed up to 28 weeks
Secondary	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.	From date of randomization until the date of CR or date of hysterectomy, assessed up to 28 weeks
Secondary	Time to achieve complete response	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.
Secondary	Relapse rates		Up to 2 years after the treatment
Secondary	Rates of fertility outcomes	Including pregnancy and live-birth rates	Up to 2 years after the treatment
Secondary	Compliance		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.

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