Clinical trial NCT05316467: Weight Management Plus Megestrol Acetate in Early-stage Endometrioid Carcinoma
Official title: Weight Management Plus Megestrol Acetate in Early-stage Endometrioid Carcinoma: Two Single-arm, Prospective and Open-label Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Endometrial Carcinoma
Obese
Overweight
Fertility Issues
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2022-04-07
Enrollment: 89
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All enrolled patients will receive enhanced lifestyle management to control weight and take Megestrol Acetate (MA) for treating EEC.
Primary purpose: TREATMENT

Brief summary: To investigate the efficacy of weight management plus megestrol acetate in obese patients with early endometrioid carcinoma（EEC）asking for fertility-sparing treatment

Detailed description: Background:

High-dosage high-efficacy progesterone, such as Megestrol Acetate (MA) and medroxyprogesterone acetate(MPA), is still the first-line treatment for women with early endometrioid endometrial cancer (EEC) who want to preserve fertility. Approximately 70% to 80% of females who meet the criteria for conservation treatment are able to achieve CR after progestin therapy, with a median time of 6-7 months, but about 20% to 30% of patients get no response or need to take longer time to achieve remission (over one year). Overweight/obesity is an independent risk factor for fertility-sparing treatment response and pregnant outcomes in young females with early endometrioid cancer, substantial evidence showed that obesity can cause relatively lower complete response（CR）rates, longer time to achieve completer remission and lower birth rates besides metabolic disorders and other adverse effects caused by obesity. Weight management has been found to improve metabolic disorders, ovarian functions and pregnant outcomes.The hypothesize is that weight management plus progestin therapy may raise CR rates and pregnant outcomes in young female EEC patients asking for fertility conservation. Previous research has shown that metformin plus MA can increase CR rates. Enhanced lifestyle management (diet control, exercise and daily behavioral guidance) may improve metabolic conditions, increase CR rates and pregnant outcomes in obese EEC patients who want to preserve fertility. Till now, no similar studies were found, so the investigators design this study to explore the efficacy of weight control in EEC fertility-sparing patients to provide new evidence for improving conservative treatment.

Objective: To investigate whether weight management plus MA improve the efficacy of preserving fertility when compared to MA alone in obese women with EEC who want fertility conservation.

Design: This study is two single-arm, prospective, open-label. Patients with early-stage endometrioid carcinoma requiring conservation treatment with BMI ≥ 24 kg/m2 will be recruited in this study and they will be divided into two arms, one is overweight group (24kg/m2≤BMI\<28kg/m2) and another is obese group (BMI≥28kg/m2). Each arm and its sample size was designed according to Simon's Two-Stage Design. All enrolled patients will receive enhanced lifestyle management to control weight and take MA for treating EEC. Hysteroscopic examination, metabolic and inflammatory indicators will be performed every 12 to16 weeks while other indexes will be evaluated every month, including weight, heart rates，blood pressure and so on.For the progestin efficacy evaluation, CR is defined as the remission of EEC to proliferative or secretory endometrium; partial response (PR) is defined as regression to simple or complex hyperplasia with or without atypia; no response (NR) is defined as the persistence of the disease; and progressive disease (PD) is defined as disease progression in patients. Two months' maintenance treatment will be recommended for patients with CR, and participants will be followed up for 2 years.

Outcomes: Primary outcome is the CR rates of the two arms (overweight and obesity group). Secondary outcomes include pregnancy rates, live birth rates, weight loss, insulin resistance, chronic inflammation indicators, time to achieve CR and the recurrence rates and so on. Safety and side events during the whole trial will be monitored in two years.

Eligibility criteria: Inclusion Criteria:

1. 18 years≤age≤45years
2. BMI (body mass index) ≥24kg/m2
3. Consent informed and signed
4. Pathologically confirmed as endometrial carcinoma Patients with endometrial specimens obtained by endometrial biopsy, diagnostic curettage or hysteroscopy and diagnosed histologically as endometrioid carcinoma, G1. If specimens are from other hospitals, they must be counseled or reconfirmed by the Department of Pathology of the Obstetrics and Gynecology Hospital of Fudan University.
5. Imaging Assessment Enhanced MRI of the pelvis and enhanced CT of the upper abdomen must be performed in 2 weeks prior to starting treatment to assess the lesions confined to the endometrial layer without clear myometrial infiltration or extrauterine involvement.
6. Have a strong desire to reproduce and ask for fertility preservation or those who insist on keeping the uterus despite no reproductive requirements.
7. 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:

1. Patients with non-endometrioid endometrial carcinoma, endometrioid endometrial carcinoma G2/G3 or other malignant tumors of the reproductive system; imaging suggests myometrial invasion, cervical involvement or extra-uterine involvement.
2. Combined with severe medical disease or liver or kidney dysfunction: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels elevate to 3 times or more of the upper limit of normal, kidney dysfunction (creatinine clearance \<30 mL/min)
3. 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.
4. Those who have received high doses of high potency progestin or oral contraceptives within the last 3 months (or those on maintenance medication).
5. Those who require hysterectomy or other methods other than conservative treatment.
6. Known or suspected pregnancy.
7. Those who has contraindications to use progestin.
8. Deep vein thrombosis, stroke, myocardial infarction.
9. Severe joint lesions that prevent walking or movement.

Primary outcomes:
measure: Pathological complete response (CR) rates
timeFrame: From date of recruitment until the date of CR, assessed up to 28 weeks.
Secondary outcomes:
measure: Pregnancy outcomes
timeFrame: up to 2 years after complete response of the last participant
measure: Weight change
timeFrame: From date of recruitment, assessed up to 28 weeks.
measure: Change of body composition
timeFrame: From date of recruitment, assessed up to 28 weeks.
measure: Change of heart rates
timeFrame: From date of recruitment, assessed up to 28 weeks.
measure: Change of blood pressures
timeFrame: From date of recruitment, assessed up to 28 weeks.
measure: Blood glucose change
timeFrame: From date of recruitment, assessed up to 28 weeks.
measure: Blood lipids change
timeFrame: From date of recruitment, assessed up to 28 weeks.
measure: Insulin resistance change
timeFrame: From date of recruitment, assessed up to 28 weeks.
measure: Ovarian reserve function change
timeFrame: From date of recruitment, assessed up to 28 weeks.
measure: Quality of life change
timeFrame: From date of recruitment, assessed up to 28 weeks.
measure: Physical activities change
timeFrame: From date of recruitment, assessed up to 28 weeks.
measure: Chronic inflammatory indexes change
timeFrame: From date of recruitment, assessed up to 28 weeks.
measure: Time of pathological complete response (CR)
timeFrame: From date of recruitment until the date of CR, assessed up to 2 years.
measure: Incidence of adverse events
timeFrame: From date of recruitment until the date of CR, assessed up to 2 years.
measure: Relapse rates
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
state: Shanghai
Study officials:
affiliation: Obstetrics & Gynecology Hospital of Fudan University
name: XIAOJUN CHEN, PhD
role: PRINCIPAL_INVESTIGATOR
References: