GnRHa + Letrozole in Obese Progestin-insensitive Endometrial Atypical Hyperplasia Patients

Obesity Clinical Trial

Official title:

Gonadotropin-releasing Hormone Agonist (GnRHa) Plus Letrozole in Obese Progestin-insensitive Endometrial Atypical Hyperplasia Patients With Conservative Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06390904
• Other study ID #: 53211030-3
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 13, 2022
• Est. completion date: June 30, 2025

Study information

• Verified date: April 2024
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To investigate the efficacy of Gonadotropin-releasing Hormone Agonist (GnRHa) plus letrozole in obese progestin-insensitive atypical endometrial hyperplasia (EAH) patients.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 29
• Est. completion date: June 30, 2025
• Est. primary completion date: June 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

• BMI=30kg/m2
• 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 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)

Related Conditions & MeSH terms

• Atypical Endometrial Hyperplasia
• Endometrial Hyperplasia
• Hyperplasia
• Obesity
• Progesterone Resistance

Intervention

Drug:
• GnRH antagonist
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 2.5mg
2.5mg po qd.

Locations

Country	Name	City	State
China	Obstetrics and Gynecology Hospital, Fudan University	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 (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.	Up to 28 weeks
Secondary	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.	During the treatment period, an average of 28 weeks
Secondary	Time to achieve CR	The median CR time will be calculated.	During the treatment period, an average of 28 weeks
Secondary	Relapse rate	Relapse will be defined as endometrial hyperplasia or endometrial cancer recurred after patients achieve CR.	Average of 2 years after the completion of the treatment
Secondary	Rate of fertility outcomes	Among patients prepared to get pregnant, fertility outcomes will be recorded.	Average of 2 years after the completion of the treatment