A Randomized Phase II Trial of Temsirolimus (NCI-Supplied Agent, NSC # 683864, IND # 61010) or the Combination of Hormonal Therapy Plus Temsirolimus in Women With Advanced, Persistent, or Recurrent Endometrial Carcinoma

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