Pazopanib Hydrochloride Followed by Chemotherapy and Surgery in Treating Patients With Soft Tissue Sarcoma

Inclusion Criteria

• Histologically or cytologically confirmed soft-tissue sarcoma, excluding alveolar and embryonal rhabdomyosarcoma, well- and dedifferentiated adipocytic sarcomas, Ewing's, osteosarcoma, or gastrointestinal stromal tumor; American Joint Committee on Cancer (AJCC) (6th Edition) Stage III or T2a Stage II or Stage IV treatment naive patients planned for resection of the primary tumor, with resectable metastatic disease
• Measurable disease greater than 5 centimeters in greatest dimension; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter for non-nodal lesions and short axis for nodal lesions to be recorded) by chest x-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI) or with calipers by clinical exam; all tumor measurements must be recorded in millimeters (or decimal fractions of centimeters)
• Intermediate or high grade lesions: 2 or 3 on a scale of 1-3 or grades 2 to 4 on a scale of 1-4
• Sarcoma located on upper (includes shoulder) or lower (includes hip) extremities or on the body wall
• Life expectancy of greater than 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status = = 80%
• No prior chemotherapy, radiotherapy, or antiangiogenic therapy
• Absolute neutrophil count (ANC) >= 1500/uL
• Hemoglobin (Hgb) >= 9.0 g/dL
• Platelets >= 100,000/uL
• Creatinine = = 50%
• Blood pressure (BP) no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility; initiation or adjustment of BP medication is permitted prior to study entry provided that the average of three BP readings on baseline assessment prior to enrollment is less than 140/90 mmHg
• Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of pazopanib will be determined following review of their cases by the Principal Investigator
• Women of child-bearing potential and men must agree to use adequate contraception
• A female is eligible to enter and participate in this study if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) or if she is of childbearing potential
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Subjects with known brain metastases and/or unresectable sarcoma
• Uncontrolled intercurrent illness including, active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac ventricular arrhythmia requiring anti-arrhythmic therapy, serious hepatic impairment, or psychiatric illness/social situations that would limit compliance with study
• Pregnant or lactating women
• Subjects with no additional active malignancy within the last 3 years
• Subjects receiving other investigational agents
• Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib or other agents used in the study
• Subjects who have both bilirubin > ULN and AST/ALT > ULN
• Subjects with a urine protein/creatinine ratio greater than 1
• Subjects with a baseline corrected QT (QTc) of equal to or greater than 480 msecs or other significant electrocardiogram (ECG) abnormalities
• Certain medications that act through the cytochrome P450 (CYP450) system are specifically prohibited in subjects receiving pazopanib and others should be avoided or administered with extreme caution and require principal investigator (PI) approval
• Strong inhibitors of CYP3A4 such as ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole may increase pazopanib concentrations and are prohibited; grapefruit juice is also an inhibitor of CYP450 and should not be taken with pazopanib
• Strong inducers of CYP3A4, such as rifampin, may decrease pazopanib concentrations, are prohibited
• Medications which have narrow t