Megestrol Acetate Plus Metformin to Megestrol Acetate in Patients With Endometrial Atypical Hyperplasia or Early Stage Endometrial Adenocarcinoma
Condition: Endometrial Atypical Hyperplasia; Endometrial Adenocarcinoma
MeSH terms: Adenocarcinoma; Uterine Neoplasms; Hyperplasia
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Megestrol acetate and metformin; Megestrol acetate
Intervention type(s): Drug; Drug
Intervention description(s): Patients will receive metformin 500 mg by mouth third daily and megestrol acetate 160 mg by mouth daily for 3 months.; Patients will receive megestrol acetate 160 mg by mouth daily for 3 months.
Other intervention name(s): Megestrol acetate: Megace; Metformin: Fortamet, Glucophage; Megestrol acetate: Megace
Intervention MeSH terms: Metformin; Megestrol; Megestrol Acetate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Endometrial Atypical Hyperplasia; Endometrial Adenocarcinoma; Conservative Medication