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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
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

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

First Posted
January 16, 2022
Last Updated
March 26, 2023
Sponsor
Fudan University
Collaborators
Peking Union Medical College Hospital
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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
No
Studies a U.S. FDA-regulated Device Product
No

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
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.
Arm Title
MA/MPA
Arm Type
Active Comparator
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 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.
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
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.
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
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
Time Frame
From date of randomization until 12 weeks after treatment is over.
Title
Relapse rates
Description
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.
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
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
Email
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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