Bevacizumab and Temsirolimus in Treating Patients With Recurrent or Persistent Endometrial Cancer

Inclusion Criteria:

* Histologically confirmed endometrial carcinoma (from primary tumor) including any of the following cell types:

  * Endometrioid adenocarcinoma
  * Serous adenocarcinoma
  * Undifferentiated carcinoma
  * Clear cell adenocarcinoma
  * Mixed epithelial carcinoma
  * Adenocarcinoma not otherwise specified
  * Mucinous adenocarcinoma
  * Squamous cell carcinoma
  * Transitional cell carcinoma
  * Mesonephric carcinoma
* Recurrent or persistent disease that is refractory to curative therapy or established treatments
* Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
* Must have ≥ 1 target lesion to assess response as defined by RECIST

  * Tumors within a previously irradiated field are designated as "non-target" lesions in the absence of documented disease progression or a biopsy to confirm persistence for ≥ 90 days after completion of radiotherapy
* Must have received 1 prior chemotherapeutic regimen for management of endometrial carcinoma

  * May have received 1 additional cytotoxic regimen for management of this disease
* Not eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, including any active GOG Phase III protocol for patients with endometrial carcinoma
* No history or evidence of CNS disease, including primary brain tumor or any brain metastases upon physical examination
* GOG performance status (PS) 0-2 (for patients who have received 1 prior regimen) OR PS 0-1 (for patients who have received 2 prior regimens)
* ANC ≥ 1,500/mcL
* Platelet count ≥ 100,000/mcL
* Creatinine ≤ 1.5 times upper limit of normal (ULN)
* Bilirubin ≤ 1.5 times ULN
* SGOT ≤ 2.5 times ULN
* Alkaline phosphatase ≤ 2.5 times ULN
* Urine protein:creatinine ratio \< 1.0 OR urine protein \< 1,000 mg by 24-hour urine collection
* INR ≤ 1.5 OR in-range INR between 2 and 3 if patient is on a stable dose of therapeutic warfarin
* PTT ≤ 1.5 times ULN
* Fasting cholesterol \< 350 mg/dL
* Fasting triglycerides \< 400 mg/dL
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Seizures allowed provided they are controlled with standard medical therapy
* No active infection requiring antibiotics, except uncomplicated urinary tract infection
* No active bleeding or pathologic conditions that carry high risk of bleeding, (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)
* No serious, non-healing wound, ulcer, or bone fracture, including abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 3 months

  * No prior underlying lesions that caused the fistula or perforation that have not been corrected
* No prior interstitial pneumonitis
* No clinically significant cardiovascular disease, including any of the following:

  * Uncontrolled hypertension, defined as systolic blood pressure (BP) \> 150 mm Hg or diastolic BP \> 90 mm Hg
  * Myocardial infarction or unstable angina within the past 6 months
  * New York Heart Association class II-IV congestive heart failure
  * Serious cardiac arrhythmia requiring medication
  * Peripheral vascular disease ≥ grade 2
* No cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
* No uncontrolled diabetes

  * Hemoglobin A1C \< 10
* No other invasive malignancies within the past 5 years, except nonmelanoma skin cancer and other specific malignancies (e.g., localized breast, head and neck, or skin cancer that completed treatment \> 3 years prior to study and remain disease-free)
* No significant traumatic injury within the past 28 days
* No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
* Concurrent prophylactic or therapeutic anticoagulation\* (e.g., warfarin) allowed
* Recovered from recent surgery, radiotherapy, or chemotherapy
* No prior bevacizumab or other VEGF pathway-targeted therapy
* No prior temsirolimus, everolimus, deforolimus, sirolimus, or any other mTor/PI3K pathway-targeted therapy
* No prior non-cytotoxic chemotherapy for management of this disease, except hormonal therapy

  * At least 1 week since prior hormonal therapy directed at the malignant tumor
* No prior therapy that contraindicates this protocol therapy
* No prior radiotherapy to any portion of the abdominal cavity or pelvis within the past 5 years, except treatment of endometrial cancer

  * Prior radiotherapy for localized cancer of the breast, head and neck, or skin is allowed, provided it was completed \> 3 years prior to study entry and patient remains free of recurrent or metastatic disease
* No prior chemotherapy for any abdominal or pelvic tumor within the past 5 years, except treatment of endometrial cancer

  * Prior adjuvant chemotherapy for localized breast cancer allowed, provided it was completed \> 3 years prior to study entry and the patient remains free of recurrent or metastatic disease
* Prior treatment with an anthracycline (i.e., doxorubicin and/or liposomal doxorubicin) allowed provided ejection fraction \< 50%
* More than 28 days since prior major surgery or open biopsy
* More than 7 days since minor surgical procedures, fine needle aspirates, or core biopsies
* At least 3 weeks since prior therapy directed at the malignant tumor, including immunologic agents
* No concurrent major surgery
* No concurrent prophylactic filgrastim (G-CSF) or thrombopoietic agents
* No concurrent amifostine or other protective reagents