Pazopanib as Front-Line Therapy in Patients With Non-Resectable or Metastatic Soft Tissue Sarcomas Who Are Not Candidates for Chemotherapy

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 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