Clinical trial NCT05247268: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Endometrial Neoplasm Malignant Stage I
Keywords: early endometrial carcinoma
fertility-preserving treatment
gonadotropin-releasing hormone analogue
aromatase inhibitors
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Peking Union Medical College Hospital
First posted: 2022-02-18
Enrollment: 104
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Complete response rates within 16 weeks of treatment
timeFrame: From date of treatment initiation until the date of CR, assessed up to 16 weeks.
Secondary outcomes:
measure: Complete response rates within 28 weeks of treatment
timeFrame: From date of treatment initiation until the date of CR, assessed up to 28 weeks.
measure: Time to achieve complete response
timeFrame: 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
measure: Adverse events
timeFrame: From date of treatment initiation until the date of CR, assessed up to 2 years
measure: Quality of life during the treatment accessed by WHOQOL-BREF
timeFrame: From date of randomization until 12 weeks after treatment is over.
measure: Relapse rates
timeFrame: up to 2 years after the treatment for each patient
measure: Change of AMH (anti-mullerian hormone ) serum level
timeFrame: From date of randomization until 24 weeks after treatment is over.
measure: The rates of fertility outcomes
timeFrame: up to 2 years after the treatment for each patient
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Obstetrics and Gynecology Hospital, Fudan University
Study officials:
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