Inclusion Criteria:

• Histologically confirmed diagnosis of nonresectable or metastatic soft tissue sarcoma. The following histologies are excluded: embryonal rhabdomyosarcoma, chondrosarcoma, osteosarcoma, Ewing tumors, primitive neuroectodermal tumors, gastrointestinal stromal tumors, dermatofibrosarcoma protuberans, inflammatory myofibroblastic sarcoma, and mixed mesodermal tumors of the uterus.
• Evaluable disease by imaging or physical exam OR measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
• Not a candidate for chemotherapy as determined by treatment physician
• Age ≥ 18 years
• ECOG performance status ≤ 2
• Normal bone marrow and organ function as defined below:
  • Absolute neutrophil count ≥ 1,500/mcl
  • Platelets ≥ 100,000/mcl
  • Hemoglobin ≥ 9.0 g/dL
  • PT or INR ≤ 1.2 x IULN (if not receiving anticoagulation therapy)
  • PTT ≤ 1.2 x IULN (if not receiving anticoagulation therapy)
  • Total bilirubin ≤ 1.5 x IULN or ≤ 3.0 x IULN with normal AST and ALT in patients with Gilbert's disease
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
  • Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 30 mL/min/1.73 m2 for patients with creatinine levels above 1.5 mg/dL
  • UPC < 1 or, if UPC ≥ 1, 24-hour urine protein < 1 g; use of urine dipstick for renal function assessment is not acceptable.

Notes:

Subjects may not have had a transfusion within 7 days of screening assessments. Concomitant elevation of bilirubin and AST/ALT above the IULN is not allowed.

Patients receiving anticoagulation therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation.

• Ability to swallow and retain oral tablets.
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion Criteria:

• Eligible for cytotoxic chemotherapy.
• Prior systemic therapy for this type of sarcoma. Neoadjuvant or adjuvant therapy more than two years prior would not apply.
• Prior treatment with any VEGFR tyrosine kinase inhibitor.
• Administration of any non-oncologic investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the first dose of pazopanib.
• Use of a strong CYP3A4 inhibitor less than 14 days prior to initiation of study treatment
• A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
• Known brain metastases.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib or other agents used in the study.
• Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity (except alopecia).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled seizure disorder, or psychiatric illness/social situations that would limit compliance with study requirements.
• Corrected QT interval (QTc) > 480 msecs.
• History of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina pectoris, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure as defined by the New York Heart Association
• Poorly controlled hypertension (defined as systolic blood pressure of ≥ 140 mmHg or diastolic blood pressure of ≥ 90 mmHg). Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure must be reassessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between antihypertensive medication initiation or adjustment and blood pressure measurement. These three values should be averaged to obtain the mean diastolic and systolic blood pressures, which must be < 140/90 mmHg in order for a patient to be eligible for the study.
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding, including (but not limited to) active peptic ulcer disease, known intraluminal metastatic lesions with risk of bleeding, inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other GI conditions with increased risk of perforation, history of abdominal fistula or intra-abdominal abscess within 28 days prior to beginning study treatment.
• Clinically significant gastrointestinal abnormalities that may affect absorption of pazopanib, including (but not limited to) malabsorption syndrome or major resection of the stomach or small bowel.
• History of cerebrovascular accident including transient ischemic attack, pulmonary embolism (PE) (including asymptomatic or previously treated PE), or untreated deep venous thrombosis within the past 6 months. Patients with DVT who are being treated with therapeutic anti-coagulating agents are eligible.
• Major surgery or trauma within 28 days prior to first dose of pazopanib and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
• Evidence of active bleeding or bleeding diathesis.
• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage. Note: lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions). Large protruding endobronchial lesions in the mail or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed. Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of thee bronchi are allowed.
• Recent hemoptysis (≥ ½ teaspoon of red blood within 8 weeks before first dose of pazopanib).
• Pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test within 14 days of study entry.
• Known HIV-positivity. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.