A Phase II, Single-Arm Study of RAD001 (Everolimus), Letrozole, and Metformin in Patients With Advanced or Recurrent Endometrial Carcinoma

The goal of this clinical research study is to learn if the combination of everolimus, letrozole, and metformin can help to control recurrent or progressive endometrial cancer. The safety of this drug combination will also be studied. Everolimus is designed to block a protein inside cancer cells that is involved in cancer growth. Letrozole is designed to block a protein from making estrogen. This may interfere with the growth of cancer cells. Metformin is commonly used to control blood sugar levels in patients with diabetes. It is designed to lower insulin levels, which may slow or stop the growth of endometrial cancer cells.

Inclusion Criteria: 1. Patients must have histologically-confirmed advanced or recurrent endometrial carcinoma (endometrioid and mixed tumors, any grade) that is refractory to curative therapy or established treatments 2. Patients must have had no more than two prior chemotherapeutic regimens for recurrent management of endometrial carcinoma. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer is not counted as a prior treatment for recurrent or advanced disease 3. Prior radiation therapy of any kind is allowed 4. All patients must have measurable disease per RECIST 1.1 defined as at least one target lesion that can be accurately measured in at least one dimension (\>/=10mm longest dimension to be recorded; Lymph nodes must be \>/=15 mm per short axis). Each lesion must be \> 20 mm when measured by palpation or conventional imaging techniques (CT or MRI - based on primary physician preference) or \>10 mm with spiral CT scan. Measurable lesions must be at least 2 times the slice thickness in millimeters. Tumors within a previously irradiated field will be designated as non-target lesions unless progression is documented. Ascites and pleural effusions are not considered measurable disease. If the measurable disease is confined to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology 5. Patients must not be of child-bearing potential. Patients are considered not of child-bearing potential if they are surgically sterile (they have undergone a total hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal for greater than 12 months. Patients in whom ovaries are present and were not previously menopausal at the time of hysterectomy, should have a serum estradiol \/= 18 years 8. GOG performance status \/= 1.5 x 10\^9/L, Platelets \>/= 100 x 10\^9/L, Hb \>9 g/dL 10. Adequate liver function as shown by: a. serum bilirubin \