Cabozantinib for Adults With Advanced Soft Tissue Sarcoma

• INCLUSION CRITERIA:
• Patients must have histologically or cytologically confirmed soft tissue sarcoma that is metastatic or unresectable and for which standard treatment that prolongs survival does not exist or is no longer effective.
• 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 for non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional techniques or as >10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam.
• Patients are allowed prior vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitors (TKI) therapy.
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of cabozantinib in patients 70%).
• Life expectancy > 3 months.
• Patients must have normal organ and marrow function as defined below:
• leukocytes greater than or equal to 3,000/mcL
• absolute neutrophil count greater than or equal to 1,500/mcL
• platelets greater than or equal to 100,000/mcL
• total bilirubin less than or equal to 1.5 times ULN
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase(SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase(SGPT) less than or equal to 2.5 times institutional upper limit of normal creatinine within normal institutional limits
• creatinine within normal institutional limits OR clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.
• hemoglobin greater than or equal to 9 g/dL
• serum albumin greater than or equal to 2.8g/dL
• lipase 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
• Any history of congenital long QT syndrome
• Any of the following within 6 months before the first dose of study treatment:
• unstable angina pectoris
• clinically-significant cardiac arrhythmias
• stroke (including transient ischemic attack (TIA), or other ischemic event)
• myocardial infarction
• thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study)
• Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
• Any of the following within 28 days before the first dose of study treatment
• intra-abdominal tumor/metastases invading GI mucosa
• active peptic ulcer disease,
• inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis
• malabsorption syndrome
• Any of the following within 6 months before the first dose of study treatment:
• abdominal fistula
• gastrointestinal perforation
• bowel obstruction or gastric outlet obstruction
• intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more that 6 months before the first dose of study treatment.
• Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy
• Other clinically significant disorders such as:
• serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
• history of organ transplant, including allogeneic bone marrow transplant
• concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
• history of major surgery as follows:

i. Major surgery within 3 months of the first dose of cabozantinib if there were no wound healing complications or within 6 months of the first dose of cabozantinib if there were wo