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

Phase 3Active Not RecruitingNCT06390904

Xiaojun Chen29 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Atypical Endometrial Hyperplasia Progesterone Resistance Obesity

Interventions

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.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

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)

Locations (2)

Tenth People's Hospital of Tongji University

Shanghai, Shanghai Municipality, China

Obstetrics and Gynecology Hospital, Fudan University

Shanghai, China

Outcomes

Primary Outcomes

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.

Time frame: Up to 28 weeks

Secondary Outcomes

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.

Time frame: During the treatment period, an average of 28 weeks

Time to achieve CR

The median CR time will be calculated.

Time frame: 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.

Time frame: 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.

Time frame: Average of 2 years after the completion of the treatment

Data from ClinicalTrials.gov

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