Everolimus and Letrozole or Hormonal Therapy to Treat Endometrial Cancer

Inclusion Criteria

• Patients must have histologically confirmed advanced (FIGO Stage III or IV), persistent, or recurrent endometrial carcinoma, which is not likely to be curable by surgery or radiotherapy. Histologic documentation of the recurrence is not required.
• All patients must have measurable disease. Measurable disease is defined by RECIST version 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be greater than or equal to 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or greater than or equal to 20 mm when measured by chest x-ray. Lymph nodes must be greater than or equal to 15 mm in short axis when measured by CT or MRI (See section 8).
• Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1 (Section 8.1). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
• Prior chemoradiotherapy for a pelvic recurrence is permitted. Prior chemotherapy in the adjuvant setting for Stage I, II or III disease is permitted.

Note: No prior chemotherapy in the setting of Stage IV disease is permitted unless the patient was without evidence of disease at the completion of chemotherapy and had at least six months of progression-free survival since the completion of chemotherapy.

Regardless of circumstances, no more than one prior chemotherapy regimen (including chemo-radiotherapy) is permitted.

• Patient must be able to take p.o. medications.
• Performance status must be 0-1.
• Patients must have adequate organ and marrow function as defined below:

NOTE: Institutional/laboratory upper limit of normal = ULN Institutional/laboratory lower limit of normal = LLN

• Bone marrow function:
• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
• Platelets greater than or equal to 100,000 cells/mcl
• Hemoglobin greater than or equal to 9 g/dL
• Coagulation
• INR less than or equal to 1.5 x ULN (or in range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin).
• Renal function:
• Creatinine less than or equal to 1.5 x ULN
• Hepatic function:
• Bilirubin less than or equal to 1.5 x ULN
• ALT and AST less than or equal to 3 x ULN
• Alkaline phosphatase less than or equal to 2.5 x ULN
• Albumin greater than or equal to 2.8 g/dL
• Lipid panel:
• Fasting serum cholesterol less than or equal to 300 mg/dL
• Fasting triglycerides less than or equal to 300 mg/
• At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: hysterectomy, resection of a lung nodule; minor: central venous access catheter placement).
• At least 4 weeks must have elapsed since the patient received any radiation therapy.
• Patients who have met the pre-entry requirements specified in Section 7.0
• Patients must have signed an approved informed consent and authorization permitting release of personal health information.
• All patients must be at least 18 years of age
• Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing a highly effective form of contraception.

During the study treatment and for 8 weeks after stopping the treatment. Highly effective contraception methods include combination of any two of the following:

• Use of oral, injected or implanted hormonal methods of contraception or;
• Placement of an intrauterine device (IUD) or intrauterine system (IUS);
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;
• Total abstinence or;
• Male/female sterilization. Women are considered post-menopausal and not of child-bearing potential