Ziv-aflibercept in Treating Patients With Locally Advanced, Unresectable, or Metastatic Gynecologic Soft Tissue Sarcoma

Inclusion Criteria:

* Histologically/cytologically confirmed soft tissue sarcoma of gynecologic tract including 1 of the following subtypes: uterine leiomyosarcoma, malignant mixed mullerian tumor/carcinosarcoma, disease originating in ovary/fallopian tube allowed
* Locally advanced/unresectable/metastatic disease
* Previously treated disease must have radiographic/clinical evidence of PD
* Measurable disease-at least 1 lesion in at least 1 dimension (longest diameter) as \>=20mm with conventional techniques or as \>=10mm with spiral CT scan
* Indicator lesions may not have been previously treated with surgery/radiotherapy/radiofrequency ablation unless PD has been confirmed
* ECOG PS 0-2 OR Karnofsky PS 60-100%
* Life expectancy\>=3 months
* WBC\>=3,000/mm\^3
* Absolute neutrophil count\>=1,500/mm\^3
* Platelet count\>=75,000/mm\^3
* Bilirubin=\<1.5xULN
* AST and ALT=\<3xULN
* INR=\<1.5 (unless on warfarin)
* Creatinine=\<1.5xULN OR creatinine clearance\>=60 mL/min
* Urine protein\<1+ by dipstick OR 24-hour urine protein\<500 mg OR urine protein:creatinine ratio\<1
* Not pregnant/nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥6 months after treatment - No other active malignancy within past 5 years except adequately treated cervical carcinoma in situ/nonmelanoma skin cancer
* No known hypersensitivity to Chinese hamster ovary cell products/other recombinant human antibodies
* No history of allergic reactions attributed to compounds of similar chemical/biological composition to study agents
* No serious/nonhealing wound/ulcer/bone fracture
* No abdominal fistula/gastrointestinal perforation/bowel obstruction/intraabdominal abscess within past 28 days
* No significant traumatic injuries within past 28 days
* No evidence of bleeding diathesis/coagulopathy
* No uncontrolled intercurrent illness including but not limited to: Ongoing/active infection, psychiatric illness or social situations that would preclude study compliance
* \<=2 prior cytotoxic chemotherapy regimen for recurrent, locally advanced or metastatic disease
* Recovered from prior therapy
* No prior antiangiogenic agent

Exclusion Criteria:

* \< 4weeks since prior chemotherapy (\<6 weeks for nitrosoureas/carmustine/mitomycin C), prior investigational treatment, radiotherapy and major surgery/open biopsy
* 1 week since prior core biopsy
* 1 month since prior thrombolytic agents
* Concurrent full-dose anticoagulants with INR\>1.5 allowed if: In-range INR (usually between 2-3) on stable dose of oral anticoagulant or low molecular weight heparin,
* OR; For patients on warfarin, the upper target for INR is ≤3 No active bleeding/pathological condition that carries a high risk of bleeding (e.g. tumor invading major vessels/known varices)
* No evidence of CNS disease including primary brain tumor/brain metastasis
* No other concurrent investigational agents - No concurrent major surgery
* No concurrent combination antiretroviral therapy for HIV-positive patients
* Clinically significant cardiovascular disease including:

  * Cerebrovascular accident within past 6 months,
  * Uncontrolled hypertension defined as BP\>150/100mmHg OR systolic BP\>180mmHg if diastolic BP\<90 mmHg, on ≥2 repeated determinations on separate days within past 3 months,
* OR; Antihypertensive medications allowed as long as dose and number of antihypertensive medications have not increased within past 2 weeks, Myocardial infarction, coronary artery bypass graft, or unstable angina within past 6 months, OR;
* OR; NYHA class III-IV congestive heart failure, serious cardiac arrhythmia requiring medication, or unstable angina pectoris within past 6 months, Clinically significant peripheral vascular disease within past 6 months
* OR; pulmonary embolism, deep vein thrombosis, or other thromboembolic event within past 6 months