Gonadotropin-releasing Hormone Agonist Combined With Letrozole Compared With Megestrol Acetate or Medroxyprogesterone Acetate Alone as Fertility-sparing Treatment in Early Endometrial Cancer
| Registry | NCT05247268 |
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| Status | Recruiting |
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| Phase | Phase 2 |
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| Study type | Interventional; randomized, parallel, masking: none, treatment |
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| Enrollment | 104 (Estimated) |
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| Sponsor | Fudan University (Other); collaborators: Peking Union Medical College Hospital |
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| Conditions | Endometrial Neoplasm Malignant Stage I |
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| Interventions | Megestrol Acetate 160 MG Oral Tablet, Medroxyprogesterone Acetate 500 MG, Triprorelin Acetate, Letrozole 2.5mg (Drug) |
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| Dates | start 2022-03-11, primary completion 2027-03-10 (estimated), completion 2027-09-10 (estimated), first posted 2022-02-18, last updated 2026-06-04 |
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| Locations | 1 site in China |
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Related Papers Related Patents Related Grants Related Experts
All trials for Endometrial Neoplasm Malignant Stage I All trials of Megestrol Acetate 160 MG Oral Tablet All trials of Medroxyprogesterone Acetate 500 MG
-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.
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+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.
+Arms and interventions
| Arm | Type | Interventions | Description |
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| GnRHa+letrozole | Experimental | Drug: Triprorelin Acetate; Drug: Letrozole 2.5mg | 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. |
| MA/MPA | Active comparator | Drug: Megestrol Acetate 160 MG Oral Tablet; Drug: Medroxyprogesterone Acetate 500 MG | 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. |
- Megestrol Acetate 160 MG Oral Tablet (Drug), also known as Megestrol Acetate: At a dosage of 160 mg/day
- Medroxyprogesterone Acetate 500 MG (Drug), also known as Medroxyprogesterone Acetate: At a dosage of 500 mg/day
- Triprorelin Acetate (Drug): Intramuscular injection of 3.75mg was given 4 weeks apart and the maximum use are 6 courses
- Letrozole 2.5mg (Drug), also known as Letrozole: At a dosage of 2.5mg/day and no more than 24 weeks
+Outcome measures
Primary outcomes
- 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 outcomes
- 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
Sex: Female, ages: 18 Years to 45 Years, accepts 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)
+Locations (1)
| Facility | City | Country | Status |
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| Obstetrics and Gynecology Hospital, Fudan University | Shanghai | China | Recruiting |
+Publications
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