Temsirolimus With or Without Megestrol and Tamoxifen in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer

Inclusion Criteria:

• Histologically* confirmed endometrial carcinoma

  • NOTE: *Histologic documentation of recurrence is not required
  • Advanced (FIGO stage III or IV), persistent, or recurrent disease that cannot be cured by surgery or radiotherapy
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (e.g., palpation, plain x-ray, CT scan, and MRI) or ≥ 10 mm by spiral CT scan

• Must have at least one "target lesion" to be used to assess response, as defined by RECIST criteria

  • Tumors within a previouslyirradiated field will be designated as "non-target" lesions unless progression isdocumented
• No sarcoma, carcinosarcoma, or leiomyosarcoma of the uterine corpus
• GOG performance status 0-2
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Total bilirubin normal
• AST ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN for patients with liver metastases)
• Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver metastases)
• Creatinine ≤ 1.5 times ULN
• Cholesterol ≤ 350 mg/dL (fasting)
• Triglycerides ≤ 400 mg/dL (fasting)
• Albumin ≥ 3.0 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• Able to take oral medication
• No known congestive heart failure
• No baseline requirement for oxygen
• No history of unprovoked deep vein thrombosis or pulmonary embolism, unless patient is maintained on anticoagulation for the duration of the study
• No concurrent serious illness that, in the opinion of the treating physician, would place the patient at unreasonable risk from study therapy
• No other invasive malignancy within the past 5 years, except non-melanoma skin cancer
• At least 4 weeks since prior major surgery (e.g, hysterectomy or resection of a lung nodule)
• At least 4 weeks since minor surgery (e.g., port-a-cath placement)

• No more than 1 prior chemotherapy regimen (including chemoradiotherapy)

  • No prior chemotherapy for stage IV disease, except in the case where the patient was without evidence of disease at the completion of chemotherapy and had at least 6 months of progression-free survival since the completion of chemotherapy
  • Prior chemoradiotherapy for a pelvic recurrence is allowed
  • Prior chemotherapy in the adjuvant setting for stage I, II, or III disease is allowed
  • No prior chemotherapy for metastatic or recurrent disease except as noted above
• No prior hormonal or biologic therapy for endometrial carcinoma
• No prior cancer treatment that would contraindicate study therapy
• No concurrent enzyme-inducing antiepileptic drugs (EIAEDs) (e.g., phenytoin, carbamazepine, or phenobarbital) or any other CYP3A4 inducer (e.g., rifampin or St. John's wort)
• No concurrent maintenance corticosteroids, except for short-term use (i.e., < 5 days)

• No concurrent prophylactic granulocyte colony-stimulating factors

  • Concurrent granulocyte colony-stimulating factors for neutropenic fever allowed
• No concurrent oral contraceptives
• No other concurrent investigational agents
• No other concurrent anticancer therapies