A Phase II Study of Tivozanib in Patients With Metastatic and Non-resectable Soft Tissue Sarcomas

Inclusion Criteria

• Patients must have histologically or cytologically confirmed sarcoma of soft tissue
• Patients must have metastatic and/or locally advanced or locally recurrent disease
• Patients must have measurable disease within 4 weeks prior to registration by RECIST 1.1, 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 computed tomography (CT) scan; tumor lesions that are situated in a previously irradiated area may be considered measurable for the purposes of this study only if there is evidence of growth of the area following a course of irradiation that cannot be attributed to necrosis or bleeding into the tumor
• Patients must have had a minimum of 1 and a maximum of 4 prior chemotherapy regimens for recurrent/metastatic disease (it will be up to the treating investigator to define what constitutes a "regimen" in each case); the last dose of systemic therapy (include tyrosine kinase inhibitors) must have been given at least 4 weeks prior to initiation of therapy; patients receiving BCNU or mitomycin C must have received their last dose of such therapy at least 6 weeks prior to initiation of therapy
• Patients with brain metastasis that have been treated with definitive surgery or radiation and have been clinically stable for 3 months following the procedure with no neurological signs or symptoms and no requirement for systemic glucocorticoids are eligible for study
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count >= 1.5 x 10^9/l
• Platelets >= 75 x 10^9/l
• Total bilirubin = = 1, then a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value 1/2 teaspoon) hemoptysis or gastrointestinal hemorrhage in the past 6 months
• Patients with evidence of active bleeding or bleeding diathesis will not be eligible for participation; recent hemoptysis would be >= 1/2 teaspoon of red blood within 8 weeks before first dose of study drug
• Patients with clinically significant GI abnormalities that may affect absorption of investigational product will not be eligible for participation; these include but are not limited to:
• Malabsorption syndrome
• Major resection of the stomach or small bowel
• Patients with a corrected QT interval (QTc) > 480 msecs using Bazett's formula (QT Interval / square root(RR interval)) will not be eligible for participation
• Patients with left ventricular ejection fraction (LVEF) = 140 mmHg or diastolic blood pressure (DBP) of >= 90mmHg] will not be eligible for participation
• Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry; following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals; at least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement; these three values will be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure; the mean SBP / DBP ratio must be < 140/90 mmHg in order for a subject to be eligible for the study
• Patients with cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months will not be eligible for participation
• Note: subjects with recent DVT who have been therapeutically coagulated for at least 6 weeks are eligible
• Patients who had major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery) will not be eligible for participation
• Patients with known endobronchial lesions and/or lesions infiltrating major pulmonary vessels will not be el