Gonadotropin-releasing Hormone Agonist (GnRHa) Plus Letrozole in Young Women with Early Endometrial Cancer

Fudan University

Status and phase: Enrolling; Phase 2

Conditions: Endometrial Neoplasm Malignant Stage I

Treatments: Drug: Letrozole 2.5mg; Drug: Triprorelin Acetate; Drug: Medroxyprogesterone Acetate 500 MG; Drug: Megestrol Acetate 160 MG Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT05247268

53211032

Details and patient eligibility

About

To see if Gonadotropin-releasing hormone analogue (GnRHa) combined with aromatase inhibitors (AIs) will achieve better complete response rate than megestrol acetate or medroxyprogesterone acetate (MA/MPA) alone as fertility-sparing treatment for patients with early endometrial carcinoma.

Full description

This will be a multicenter randomized controlled study to evaluate the treatment effects and adverse events of GnRHa plus AIs compared with MA/MPA in primary EEC patients.In this study, young patients (18-45 years) diagnosed as EEC for the first time seeking for fertility preserving treatment at the Obstetrics and Gynecology Hospital of Fudan University were screened. Patients were randomly assigned (1:1) to GnRHa+letrozole group (triprorelin acetate, intramuscular injection of 3.75mg was given 4 weeks apart and the maximum use are 6 courses. letrozole, 2.5mg oral daily and no more than 24 weeks) or MA/MPA group (160 mg oral MA daily or 500 mg oral MPA daily).

Hysteroscopy will be performed every 3 months during treatment to evaluate the treatment effects. For patients with EEC, complete response (CR) is defined as the reversion of endometrial carcinoma to proliferative or secretory endometrium; partial response (PR) is defined as regression to simple or complex hyperplasia with or without atypia; Stable disease (SD) is defined as the persistence of the disease; and progressive disease (PD) is defined as the progression of endometrial lesions. Continuous therapies will be needed in PR, SD or PD.The primary endpoint was cumulative complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were cumulative CR rate at 28weeks of treatment, adverse events, recurrent rate, pregnancy rate, effects on ovarian function and quality of life of patients.

Enrollment: 104 estimated patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Consent informed and signed
• Primarily have a confirmed diagnosis of early-stage endometrial cancer (endometrioid, grade I, without myometrial inva- sion) ) based upon endometrial biopsy, diagnostic curettage or hysteroscopy
• No signs of suspicious myometrial invasion or extrauterine metastasis by enhanced magnetic resonance imaging (MRI), enhanced computed tomography (CT) or transvaginal ultrasonography (TVUS)
• Have a strong desire for remaining reproductive function or uterus
• Have good compliance and follow-up conditions, and patients are willing to follow up in Obstetrics and Gynecology Hospital of Fudan University in time

Exclusion criteria

• Pathologically confirmed as endometrial cancer with suspicious myometrial invasion or extrauterine metastasis
• Recurrent endometrial cancer
• Combined with severe medical disease or severely impaired liver and kidney function
• Patients with other types of endometrial cancer or other malignant tumors of the reproductive system; patients with breast cancer or other hormone- dependent tumors that cannot be used with progesterone
• Those who require hysterectomy or other methods other than conservative treatment with drugs
• Known or suspected pregnancy
• Contraindication for Medroxyprogesterone Acetate, Megestrol Acetate, Triprorelin Acetate, Letrozole or pregnancy
• Hormone treatment within 3 months before entering the trial;
• Acute severe disease such as stroke or heart infarction or a history of thrombosis disease
• Smoker(>15 cigarettes a day)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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104 participants in 2 patient groups

GnRHa+letrozole

Experimental group

Description:

Patients will be stratified into BMI≥28kg/m2 group and BMI\<28kg/m2 group. Patients in BMI≥28kg/m2 or BMI\<28kg/m2 group will be randomly assigned (1:1) to GnRHa+letrozole group or MA/MPA group. Patients who will be assigned to GnRHa+letrozole group will receive triprorelin acetate (intramuscular injection of 3.75mg was given 4 weeks apart and the maximum use are 6 courses) plus letrozole (2.5mg oral daily and no more than 24 weeks). Then every 3 months, an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded.

Treatment:

Drug: Triprorelin Acetate

Drug: Letrozole 2.5mg

MA/MPA

Active Comparator group

Description:

Patients will be stratified into BMI≥28kg/m2 group and BMI\<28kg/m2 group. Patients in BMI≥28kg/m2 or BMI\<28kg/m2 group were randomly assigned (1:1) to GnRHa+letrozole group or MA/MPA group.Patients assigned to MA/MPA group will receive MA/MPA (160 mg oral MA daily or 500 mg oral MPA daily).Then every 3 months, an hysteroscopy will be used to evaluate the endometrial condition, and the findings will be recorded.

Treatment:

Drug: Megestrol Acetate 160 MG Oral Tablet

Drug: Medroxyprogesterone Acetate 500 MG