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

Endometrial Neoplasm Malignant Stage I Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05247268
• Other study ID #: 53211032
• Status: Recruiting
• Phase: Phase 2
• Start date: March 11, 2022
• Est. completion date: March 10, 2025

Study information

• Verified date: April 2024
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 104
• Est. completion date: March 10, 2025
• Est. primary completion date: March 10, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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)

Related Conditions & MeSH terms

• Endometrial Neoplasm Malignant Stage I
• Endometrial Neoplasms
• Neoplasms

Intervention

Drug:
• Megestrol Acetate 160 MG Oral Tablet
At a dosage of 160 mg/day
• Medroxyprogesterone Acetate 500 MG
At a dosage of 500 mg/day
• Triprorelin Acetate
Intramuscular injection of 3.75mg was given 4 weeks apart and the maximum use are 6 courses
• Letrozole 2.5mg
At a dosage of 2.5mg/day and no more than 24 weeks

Locations

Country	Name	City	State
China	Obstetrics and Gynecology Hospital, Fudan University	Shanghai	Shanghai, China

Sponsors (2)

Lead Sponsor	Collaborator
Fudan University	Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (22)

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* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rates within 16 weeks of treatment	The cumulative 16-week CR rates will be calculated in two groups	From date of treatment initiation until the date of CR, assessed up to 16 weeks.
Secondary	Complete response rates within 28 weeks of treatment	The cumulative 28-week CR rates will be calculated in two groups	From date of treatment initiation until the date of CR, assessed up to 28 weeks.
Secondary	Time to achieve complete response	The median CR time will be calculated in two groups	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
Secondary	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.	From date of treatment initiation until the date of CR, assessed up to 2 years
Secondary	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	From date of randomization until 12 weeks after treatment is over.
Secondary	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.	up to 2 years after the treatment for each patient
Secondary	Change of AMH (anti-mullerian hormone ) serum level	AMH (anti-mullerian hormone ) will be assessed at baseline and every 12-16 weeks.	From date of randomization until 24 weeks after treatment is over.
Secondary	The rates of fertility outcomes	The percentage of pregnancy and live-birth will be counted.	up to 2 years after the treatment for each patient