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

Primary Purpose

Endometrial Neoplasm Malignant Stage I

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Megestrol Acetate 160 MG Oral Tablet

Medroxyprogesterone Acetate 500 MG

Triprorelin Acetate

Letrozole 2.5mg

About this trial

This is an interventional treatment trial for Endometrial Neoplasm Malignant Stage I focused on measuring early endometrial carcinoma, fertility-preserving treatment, gonadotropin-releasing hormone analogue, aromatase inhibitors

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleAccepts 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)

Sites / Locations

Obstetrics and Gynecology Hospital, Fudan UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

GnRHa+letrozole

MA/MPA

Arm 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.

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.

Outcomes

Primary Outcome Measures

Complete response rates within 16 weeks of treatment

The cumulative 16-week CR rates will be calculated in two groups

Secondary Outcome Measures

Complete response rates within 28 weeks of treatment

The cumulative 28-week CR rates will be calculated in two groups

Time to achieve complete response

The median CR time will be calculated in two groups

Adverse events

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

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

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

AMH (anti-mullerian hormone ) will be assessed at baseline and every 12-16 weeks.

The rates of fertility outcomes

The percentage of pregnancy and live-birth will be counted.

Full Information

NCT ID

NCT05247268

First Posted

January 16, 2022

Last Updated

March 26, 2023

Sponsor

Fudan University

Collaborators

Peking Union Medical College Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05247268

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 11, 2022 (Actual)

Primary Completion Date

March 10, 2024 (Anticipated)

Study Completion Date

March 10, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fudan University

Collaborators

Peking Union Medical College Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Endometrial Neoplasm Malignant Stage I

Keywords

early endometrial carcinoma, fertility-preserving treatment, gonadotropin-releasing hormone analogue, aromatase inhibitors

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

104 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

GnRHa+letrozole

Arm Type

Experimental

Arm Description

Arm Title

MA/MPA

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Megestrol Acetate 160 MG Oral Tablet

Other Intervention Name(s)

Megestrol Acetate

Intervention Description

At a dosage of 160 mg/day

Intervention Type

Drug

Intervention Name(s)

Medroxyprogesterone Acetate 500 MG

Other Intervention Name(s)

Medroxyprogesterone Acetate

Intervention Description

At a dosage of 500 mg/day

Intervention Type

Drug

Intervention Name(s)

Triprorelin Acetate

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Letrozole 2.5mg

Other Intervention Name(s)

Letrozole

Intervention Description

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

Primary Outcome Measure Information:

Title

Complete response rates within 16 weeks of treatment

Description

The cumulative 16-week CR rates will be calculated in two groups

Time Frame

From date of treatment initiation until the date of CR, assessed up to 16 weeks.

Secondary Outcome Measure Information:

Title

Complete response rates within 28 weeks of treatment

Description

The cumulative 28-week CR rates will be calculated in two groups

Time Frame

From date of treatment initiation until the date of CR, assessed up to 28 weeks.

Title

Time to achieve complete response

Description

The median CR time will be calculated in two groups

Time Frame

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

Title

Adverse events

Description

Time Frame

From date of treatment initiation until the date of CR, assessed up to 2 years

Title

Quality of life during the treatment accessed by WHOQOL-BREF

Description

Time Frame

From date of randomization until 12 weeks after treatment is over.

Title

Relapse rates

Description

Time Frame

up to 2 years after the treatment for each patient

Title

Change of AMH (anti-mullerian hormone ) serum level

Description

AMH (anti-mullerian hormone ) will be assessed at baseline and every 12-16 weeks.

Time Frame

From date of randomization until 24 weeks after treatment is over.

Title

The rates of fertility outcomes

Description

The percentage of pregnancy and live-birth will be counted.

Time Frame

up to 2 years after the treatment for each patient

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Facility Information:

Facility Name

Obstetrics and Gynecology Hospital, Fudan University

City

Shanghai

State/Province

Shanghai, China

ZIP/Postal Code

200011

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xiaojun Chen, PhD

Phone

862163455055

cxjlhjj@163.com

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data will be shared after this research being published,without patients personal information.

IPD Sharing Time Frame

Data will be avaliable since this research being published

IPD Sharing Access Criteria

Institutes or researchers who require the data should contact the principle investigator Prof.Xiaojun Chen via email that after this study being published.

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

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