Pazopanib Hydrochloride in Treating Patients With Advanced Angiosarcoma

Exclusion Criteria

• •Prior malignancy:
• •Subjects with a history of a prior malignancy other than angiosarcoma who have been disease-free for at least 2 years prior to the first dose of study drug and/or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
• •History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medications for 3 months prior to first dose of study drug; screening with CNS imaging studies (CT or magnetic resonance imaging \[MRI\]) is required only if clinically indicated or if the subject has a history of CNS metastases
• •Clinically significant gastrointestinal (GI) abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
• •* Active peptic ulcer disease
• •* Known intraluminal metastatic lesion/s with risk of bleeding
• •* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
• •* History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
• •* Clinically significant (\> 1/2 teaspoon) hemoptysis or gastrointestinal hemorrhage in the past 6 months
• •Evidence of active bleeding or bleeding diathesis; recent hemoptysis (\>= 1/2 teaspoon of red blood within 8 weeks before first dose of study drug)
• •Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
• •* Malabsorption syndrome
• •* Major resection of the stomach or small bowel
• •Corrected QT interval (QTc) \> 480 msecs using Bazett's formula
• •Left ventricular ejection fraction \< 50%
• •History of any one or more of the following cardiovascular conditions within the past 6 months:
• •* Cardiac angioplasty or stenting
• •* Myocardial infarction
• •* Unstable angina
• •* Coronary artery bypass graft surgery
• •* Symptomatic peripheral vascular disease
• •* Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
• •Poorly controlled hypertension (defined as systolic blood pressure \[SBP\] of \>= 140 mmHg or diastolic blood pressure \[DBP\] of \>= 90mmHg); 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 should 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
• •Cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
• •* Note: subjects with recent DVT who have been therapeutically coagulated for at least 6 weeks are eligible
• •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)
• •Evidence of active bleeding or bleeding diathesis; recent hemoptysis (\>= ½ teaspoon of red blood within 8 weeks before first dose of study drug)
• •Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels (Note: tumor abutting the vessel is acceptable, but contiguous tumor and vessel is not; CT with contrast is strongly recommended to evaluate such lesions)
• •Abnormal serum calcium, magnesium, or potassium levels
• •Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
• •Use of any prohibited medication within the timeframes
• •Treatment with any of the following therapies:
• •* Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib hydrochloride OR
• •* Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
• •* Patients who require chronic use of strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers including but not limited to grapefruit juice
• •Any ongoing toxicity from prior anti-cancer therapy that is \> Grade 1 (except hemoglobin value) and/or that is progressing in severity, except alopecia
• •Previous exposure to pazopanib hydrochloride or a vascular endothelial growth factor receptor (VEGFR) targeted kinase therapy, except for bevacizumab or VEGFR-Trap (Aflibercept)
• •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib