Pazopanib Hydrochloride and Topotecan Hydrochloride in Treating Patients With Metastatic Soft Tissue and Bone Sarcomas

Exclusion Criteria

• •Patients with any of the following sarcoma histologic subtypes will not be eligible for participation:
• •* Alveolar soft-part sarcoma
• •* Chondrosarcoma
• •* Dermatofibrosarcoma
• •* Ewing sarcoma
• •* Gastrointestinal stromal tumor (GIST)
• •* Kaposi sarcoma (non-human immunodeficiency virus \[HIV\] and HIV related disease)
• •* Mixed mesodermal tumor/carcinosarcoma
• •* Low grade (grade 1) sarcomas
• •* Rhabdomyosarcoma (embryonal, alveolar, pleomorphic)
• •* Interdigitating dendritic sarcoma
• •* Giant cell tumor of the bone
• •Patients must not have received prior treatment with pazopanib or topotecan
• •Patients must not have an active secondary malignancy
• •Prior malignancy, unless they have been disease-free for 3 years, or have a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma
• •Clinically significant gastrointestinal 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 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
• •History of any one or more of the following cardiovascular conditions within the past 12 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 (or 150/90 mm Hg, if this criterion deemed safe by principal investigator \[PI\] and the quality assurance monitor \[QAM\]) in order for a patient to be eligible for the study
• •Patients with a history of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism, or untreated deep venous thrombosis (DVT); patients with DVT must have received appropriate therapy for at least 6 months to be considered 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
• •Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage
• •* Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed
• •* Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed
• •Recent hemoptysis (\>= 1/2 teaspoon \[2.5 mL\]) of red blood within 8 weeks before first dose of study drug
• •Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with patient's safety, provision of informed consent, or compliance to study procedures
• •Unable or unwilling to discontinue use of inducers and inhibitors of cytochrome P450 (CYP450) listed for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study; cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates can be administered, but investigators will need to be aware of possible increased or decreased effectiveness of the non-study drug and this should be recorded in concomitant medications; breast cancer resistance protein (BCRP) and p-glycoprotein (PgP) inducers and inhibitors will be also prohibited
• •Treatment with any of the following anti-cancer therapies:
• •* Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of therapy
• •* 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 therapy
• •Administration of any non-oncologic investigational drug within 30 days or 5 half-lives whichever is longer prior to receiving the first dose of study treatment
• •Any ongoing toxicity related to prior anti-cancer therapy that is \> grade 1 and/or that is progressing in severity (exceptions include alopecia, fatigue, and hematologic toxicities)
• •Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or topotecan