Gonadotropin-releasing Hormone Agonist (GnRHa) Plus Letrozole In Young Women With Early Endometrial Cancer

Sponsor

Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05247268

Collaborator

Peking Union Medical College Hospital (Other)

104

Enrollment

Location

Arms

35.7

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Neoplasm Malignant Stage I	Drug: Megestrol Acetate 160 MG Oral Tablet Drug: Medroxyprogesterone Acetate 500 MG Drug: Triprorelin Acetate Drug: Letrozole 2.5mg	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Gonadotropin-releasing Hormone Agonist Combined With Letrozole Compared With Megestrol Acetate or Medroxyprogesterone Acetate Alone as Fertility-sparing Treatment in Early Endometrial Cancer

Actual Study Start Date :

Mar 11, 2022

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GnRHa+letrozole 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.	Drug: Triprorelin Acetate Intramuscular injection of 3.75mg was given 4 weeks apart and the maximum use are 6 courses Drug: Letrozole 2.5mg At a dosage of 2.5mg/day and no more than 24 weeks Other Names: Letrozole
Active Comparator: MA/MPA 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.	Drug: Megestrol Acetate 160 MG Oral Tablet At a dosage of 160 mg/day Other Names: Megestrol Acetate Drug: Medroxyprogesterone Acetate 500 MG At a dosage of 500 mg/day Other Names: Medroxyprogesterone Acetate

Arm

Intervention/Treatment

Experimental: GnRHa+letrozole

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.

Drug: Triprorelin Acetate

Intramuscular injection of 3.75mg was given 4 weeks apart and the maximum use are 6 courses

Drug: Letrozole 2.5mg

At a dosage of 2.5mg/day and no more than 24 weeks

Other Names:

Letrozole

Active Comparator: MA/MPA

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.

Drug: Megestrol Acetate 160 MG Oral Tablet

At a dosage of 160 mg/day

Other Names:

Megestrol Acetate

Drug: Medroxyprogesterone Acetate 500 MG

At a dosage of 500 mg/day

Other Names:

Medroxyprogesterone Acetate

Outcome Measures

Primary Outcome Measures

Complete response rates within 16 weeks of treatment [From date of treatment initiation until the date of CR, assessed up to 16 weeks.]
The cumulative 16-week CR rates will be calculated in two groups

Secondary Outcome Measures

Complete response rates within 28 weeks of treatment [From date of treatment initiation until the date of CR, assessed up to 28 weeks.]
The cumulative 28-week CR rates will be calculated in two groups
Time to achieve complete response [From date of treatment initiation until the date of CR or date of hysterectomy,From date of randomization until the date of CR, assessed up to 2 years]
The median CR time will be calculated in two groups
Adverse events [From date of treatment initiation until the date of CR, assessed up to 2 years]
Adverse events related with Medroxyprogesterone Acetate, Megestrol Acetate, Triprorelin Acetate and Letrozole. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be recorded, as well as incidence of adverse events.
Quality of life during the treatment accessed by WHOQOL-BREF [From date of randomization until 12 weeks after treatment is over.]
Quality of life will be assessed at baseline, 4 weeks and every 12-16 weeks of treatment, using WHOQOL-BREF scale including assessment on pain, energy,sleep,mobil,activity,medication,work,positive feeling,think,esteem,body,negtivity,spirit,relationship,support,sex,safety,home,finance,service,information, environment,leisure,transport
Relapse rates [up to 2 years after the treatment for each patient]
All enrolled patients will be followed up for 2 years. During the following-up period, if patients recur after complete response, they will be counted and the number of recurrence will be divided by number of patients followed up, then we can get the relapse rates. Comparison will be performed between two groups.
Change of AMH (anti-mullerian hormone ) serum level [From date of randomization until 24 weeks after treatment is over.]
AMH (anti-mullerian hormone ) will be assessed at baseline and every 12-16 weeks.
The rates of fertility outcomes [up to 2 years after the treatment for each patient]
The percentage of pregnancy and live-birth will be counted.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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)