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

Exclusion Criteria

• •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