To investigate the efficacy of weight management plus megestrol acetate in obese patients with early endometrioid carcinoma（EEC）asking for fertility-sparing treatment
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
89
* dietary guidance * exercise guidance * lifestyle intervention
enrolled participants will take Megestrol Acetate 160mg daily
Obstetrics and Gynecology Hospital, Fudan University
Shanghai, Shanghai Municipality, China
RECRUITINGPathological complete response (CR) rates
The 28-week CR rates will be calculated in two arms
Time frame: From date of recruitment until the date of CR, assessed up to 28 weeks.
Pregnancy outcomes
For patients have a desire for fertility, pregnancies, births and related outcomes will be counted, and the rate of pregnancy will be counted as number of pregnancies/ number of patients trying to fertility in the following period.
Time frame: up to 2 years after complete response of the last participant
Weight change
Body weight will be recorded every month and compare its change during the trial in kilograms.
Time frame: From date of recruitment, assessed up to 28 weeks.
Change of body composition
Assess the improvement of body composition, the investigators will detect body composition with InBody machine and calculate changes of the indicated indexes.
Time frame: From date of recruitment, assessed up to 28 weeks.
Change of heart rates
Record heart rates in bpm (beats per minute) every 12-16 weeks and calculate its change during the trial.
Time frame: From date of recruitment, assessed up to 28 weeks.
Change of blood pressures
Record blood pressure (both of systolic and diastolic pressures) every 12-16 weeks and compare its change during the treatment.
Time frame: From date of recruitment, assessed up to 28 weeks.
Blood glucose change
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Assess fasting glucose levels each 3 to 4 months and calculate changes during the trial in mmol/L.
Time frame: From date of recruitment, assessed up to 28 weeks.
Blood lipids change
Assess blood lipids levels each 3 to 4 months and compare their change during the treatment.
Time frame: From date of recruitment, assessed up to 28 weeks.
Insulin resistance change
Assess fasting insulin levels each 3 to 4 months and compare their changes during the trial.
Time frame: From date of recruitment, assessed up to 28 weeks.
Ovarian reserve function change
Detect serum Anti-Mullerian Hormone (AMH) levels each 3 or 4 months and calculate its change.
Time frame: From date of recruitment, assessed up to 28 weeks.
Quality of life change
Collect quality of life questionnaire (SF-36 and IWQOL-LITE) every 12-16 weeks and count scores.
Time frame: From date of recruitment, assessed up to 28 weeks.
Physical activities change
Collect physical activities questionnaire（IPAQ）and compare scores changes through conservative treatment.
Time frame: From date of recruitment, assessed up to 28 weeks.
Chronic inflammatory indexes change
Detect chronic inflammatory indexes, including TNF-α(tumor necrosis factor), IL-1 and IL-6, and calculate changes through the whole treatment period.
Time frame: From date of recruitment, assessed up to 28 weeks.
Time of pathological complete response (CR)
Time of histologic regression from EC to proliferative or secretory endometrium
Time frame: From date of recruitment until the date of CR, assessed up to 2 years.
Incidence of adverse events
Adverse events related with MA and weight control. 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 recruitment until the date of CR, assessed up to 2 years.
Relapse rates
All enrolled patients will be followed up for 2 years. During the following-up period, if patients recur after complete regression, they will be counted and the number of recurrence will be divided by number of patients followed up, then the investigators can get the relapse rates. Comparison will be performed between two groups.
Time frame: up to 2 years after the treatment for each patient