A Phase II Study of VEGF-Trap in Recurrent or Metastatic Gynecologic Soft-Tissue Sarcomas

Inclusion Criteria:

- Histologically or cytologically confirmed soft tissue sarcoma of the gynecologic
tract, including 1 of the following subtypes: uterine leiomyosarcoma, malignant mixed
mullerian tumor/carcinosarcoma, disease originating in the ovary or fallopian tube
allowed

- Locally advanced, unresectable, or metastatic disease

- Previously treated disease must have radiographic or clinical evidence of progressive
disease

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
20 mm with conventional techniques or as >= 10 mm with spiral CT scan

- Indicator lesions may not have been previously treated with surgery, radiotherapy, or
radiofrequency ablation unless progressive disease has been confirmed

- No evidence of CNS disease, including primary brain tumor or brain metastasis

- ECOG performance status (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 =< 1.5 times upper limit of normal (ULN)

- AST and ALT =< 3 times ULN

- INR =< 1.5 (unless on warfarin)

- Creatinine =< 1.5 times ULN 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 or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study treatment

- No other active malignancy within the past 5 years except adequately treated cervical
carcinoma in situ or nonmelanoma skin cancer

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to study agents

- No serious or nonhealing wound, ulcer, or bone fracture

- No abdominal fistula, gastrointestinal perforation, bowel obstruction, or
intra-abdominal abscess within the past 28 days

- No significant traumatic injuries within the past 28 days

- No clinically significant cardiovascular disease, including any of the following:

- Cerebrovascular accident within the past 6 months,

- Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg OR
systolic BP > 180 mm Hg if diastolic BP < 90 mm Hg, on ≥ 2 repeated
determinations on separate days within the past 3 months,

- OR; Antihypertensive medications allowed, as long as the dose and number of
antihypertensive medications have not been increased within the past 2 weeks,
Myocardial infarction, coronary artery bypass graft, or unstable angina within the
past 6 months, OR;

- OR; New York Heart Association class III-IV congestive heart failure, serious cardiac
arrhythmia requiring medication, or unstable angina pectoris within the past 6
months, Clinically significant peripheral vascular disease within the past 6 months
(i.e., limiting activities of daily living or the presence of pain at rest),

- OR; pulmonary embolism, deep vein thrombosis, or other thromboembolic event within
the past 6 months

- No evidence of bleeding diathesis or coagulopathy

- No uncontrolled intercurrent illness including, but not limited to, the following:
Ongoing or active infection, psychiatric illness or social situations that would
preclude study compliance

- No more than 2 prior cytotoxic chemotherapy regimen for recurrent, locally advanced,
or metastatic disease

- Recovered from prior therapy

- No prior antiangiogenic agent

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, carmustine, or
mitomycin C)

- At least 4 weeks since prior investigational treatment

- At least 4 weeks since prior radiotherapy

- At least 4 weeks since prior major surgery or open biopsy

- At least 1 week since prior core biopsy

- At least 1 month since prior thrombolytic agents

- Concurrent full-dose anticoagulants (e.g., warfarin) with INR > 1.5 allowed provided
all the following criteria are met:, In-range INR (usually between 2-3) on a stable
dose of oral anticoagulant or on a stable dose of low molecular weight heparin,

- OR; For patients on warfarin, the upper target for INR is ≤ 3 No active bleeding or
pathological condition that carries a high risk of bleeding (e.g., tumor invading
major vessels or known varices)

- No other concurrent investigational agents

- No concurrent major surgery

- No concurrent combination antiretroviral therapy for HIV-positive patients