Clinical trial NCT01968317: Megestrol Acetate Plus Metformin to Megestrol Acetate in Patients With Endometrial Atypical Hyperplasia or Early Stage Endometrial Adenocarcinoma
Official title: Megestrol Acetate Plus Metformin to Megestrol Acetate in Patients With Endometrial Atypical Hyperplasia or Early Stage Endometrial Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometrial Atypical Hyperplasia
Endometrial Adenocarcinoma
Keywords: Endometrial Atypical Hyperplasia
Endometrial Adenocarcinoma
Conservative Medication
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Fudan University
name: Shanghai 6th People's Hospital
name: Zhejiang Cancer Hospital
name: Shanghai Changning Maternity & Infant Health Hospital
First posted: 2013-10-24
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if megestrol acetate plus metformin will be more effective in returning the endometrial tissue to a normal state than megestrol acetate alone in patients with endometrial atypical hyperplasia or early stage endometrial adenocarcinoma.

Detailed description: After diagnosed of endometrial atypical hyperplasia(EAH) or type I endometrial cancer(EC) by dilatation and curettage (D\&C) or hysteroscopy, patients will be enrolled. Age, waist circumstances, blood pressure, basic history of infertility, blood pressure, serum lipid level and side effects will be collected. Blood tests, including triglycerides, high density lipoprotein-cholesterol, fasting blood glucose, liver and kidney function will be performed before treatment to evacuate their metabolic conditions.

Patients are randomized to 1 of 2 treatment groups. Patients will receive metformin 500 mg by mouth third daily and megestrol acetate 160 mg by mouth daily for 3 months on Arm I. Patients will receive megestrol acetate 160 mg PO daily for 3 months on Arm II. Then an hysteroscope will be used to evaluate the endometrial condition, and the findings will be recorded. For patients with EAH, complete response (CR) is defined as the reversion of endometrial atypical hyperplasia to proliferative or secretory endometrium; partial response (PR) is defined as regression to simple or complex hyperplasia without atypia; no response (NR) is defined as the persistence of the disease; and progressive disease (PD) is defined as the appearance of endometrial cancer in patients. EAH after treatment will be defined as PR in patients with EC. Continuous therapies will be needed in PR, NR or PD.

After completion of study treatment, 3 months of maintenance treatment will be recommended for patients with CR, and they will be followed up for 2 years.

In addition, we've already had a pilot study in 19 patients primarily diagnosed of endometrial atypical hyperplasia from August 2012 to April 2013. 10 patients were in Arm I and 9 patients were in Arm II. Metabolic syndrome were evaluated among all subjects. After treatment, megestrol acetate plus metformin worked better than megestrol acetate alone. But two arms showed no difference in NR patients, which may suggest metformin just worked as an antitumor drug more than an insulin sensitizer. More supportive researches are needed to verify it.

Eligibility criteria: Inclusion Criteria:

* Be between the ages of 18-45 years old
* Primarily have a confirmed diagnosis of endometrial atypical hyperplasia based upon D\&C or hysteroscopy

  * OR primarily have a confirmed diagnosis of endometrial adenocarcinoma(G1, low tumor grade), based upon D\&C or hysteroscopy, and three MRI parameters shows there's no myometrial invasion, extension beyond corpus, or enlarged lymph nodes
* Have a desire for remaining reproductive function or uterus
* Need to be able to undergo correlative treatment and follow-up

Exclusion Criteria:

* Have a history of serious liver or renal dysfunction
* Have a confirmed diagnosis of malignant tumor in genital system
* Have taken oral contraceptive or other medicine for the treatment of endometrial hyperplasia in the past 6 months
* Ask for removal of the uterus or other conservative treatment
* serum CA-125 \> 35 Um/L

Primary outcomes:
measure: Cumulative CR Rates Within 16 Weeks
timeFrame: 16 weeks after initial treatment
Secondary outcomes:
measure: Cumulative CR Rates Within 32 Weeks
timeFrame: 32 weeks after initial treatment
measure: Recurrence Rate
timeFrame: through study completion, a median time of 33 months
measure: Pregnancy Rate
timeFrame: through study completion, a median time of 33 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Obstetrics and Gynecology Hospital, Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Changning Maternity & Infant Health Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Obstetrics & Gynecology Hospital of Fudan University
name: Xiaojun Chen, PhD
role: STUDY_CHAIR
References: