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

Inclusion Criteria

• Patients must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up
• Patients must have a histologically confirmed diagnosis of:
• Metastatic soft tissue sarcomas (non-liposarcoma)
• Metastatic osteosarcoma
• Metastatic liposarcoma- high grade, de-differentiated, or myxoid Note: pathology is not required to be reviewed at the treating institution; a copy of the pathology report is sufficient for eligibility purposes
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Patients must have measurable disease within 4 weeks prior to registration by Response Evaluation Criteria In Solid Tumors (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 >= 10mm with spiral computed tomography (CT) scan
• 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 investigator to determine what constitutes a "regimen" in each case; the last dose of systemic therapy much have been given at least 4 weeks prior to initiation of therapy; patients receiving BCNU or mitomycin C must have received their last dose at least 6 weeks prior to initiation of therapy
• Patients with brain metastasis are eligible for participation only if they have been treated with definitive surgery or radiation (surgery ± radiotherapy, radiosurgery, or gamma knife) and meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 12 week interval
• Absolute neutrophil count (ANC) >= 1.5 X 10^9/L (tested within 7 days prior to Registration)
• Hemoglobin >= 9 g/dL (5.6 mmol/L)
• Subjects may not have had a transfusion within 7 days of screening assessment
• Platelets >= 100 X 10^9/L
• Subjects may not have had a transfusion within 7 days of screening assessment
• Prothrombin time (PT) or international normalized ratio (INR) = 1.5 mg/dL: calculated creatinine clearance (ClCR) >= 30 mL/min to >= 50 mL/min
• Urine protein to creatinine ratio (UPC) = 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value 12 months)
• FOCBP must have a negative pregnancy test within 7 days prior to registration on study
• Note: female patients who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug
• Are able to swallow and retain oral tablets

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
• His