study of pazopanib in the treatment of osteosarcoma metastatic to the lung

Conditions: Osteosarcoma; Metastatic Osteosarcoma

Summary: the purpose of this study is to determine the 4-month progression-free survival (pfs), with demonstrated increase in tumor doubling time, of eligible subjects treated with pazopanib according to recist version 1.1 guidelines.


Eligibility criteria:
inclusion criteria: * written informed consent or assent * age \> or = to 16 years * histologically confirmed diagnosis of osteosarcoma with lung metastasis, who have progressed on the prior line of therapy, or relapsed * ineligible for curative pulmonary metastasectomy * eastern cooperative oncology group (ecog) performance status of 0-2 * measurable disease per response evaluation criteria in solid tumors (recist) version 1.1 guidelines. at least one measurable lesion must be in the lungs. * eligible subjects are required to have \> or = to 1 line of multi-agent chemotherapy either neoadjuvantly or adjuvantly. subjects may have had 0-2 lines of therapy for metastatic disease. * measured cardiac ejection fraction \> or = to 50% or the institutional lower limit of normal by echocardiogram or muga scan. * adequate organ system function. * females must be either non-child bearing potential or have a negative pregnancy test within 3 to 5 days prior to the first dose of study drug. exclusion criteria: * children not in the care or custody of a biological parent, adoptive parent, appointed legal guardian, or legally appointed foster care. * prior exposure to vegfr tyrosine kinase inhibitor (small molecule or antibody) or vegfr antibody. * prior malignancy. note: subjects who have had another malignancy and have been disease-free for 3 years, 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, unless previously treated, asymptomatic, and off steroids and anti-seizure medication for 6 months prior to first dose of study drug * clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding. * clinically significant gastrointestinal abnormalities that may affect absorption of investigational product. * presence of uncontrolled infection. * corrected qt interval (qtc) \> 480 msecs using bazett's formula. * history of certain cardiovascular conditions within the past 6 months. * class ii-iv congestive heart failure, as defined by the new york heart association * poorly controlled hypertension \[defined as systolic blood pressure (sbp) of ≥ 140 mmhg or diastolic blood pressure (dbp) of ≥ 90mmhg\]. * history of cerebrovascular accident including transient ischemic attack (tia), pulmonary embolism or untreated deep venous thrombosis (dvt) within the past 6 months. * prior major surgery or trauma within 28 days prior to the protocol-mandated 4-week drug holiday and/or presence of any non-healing wound, fracture, or ulcer. * evidence of active bleeding or bleeding diathesis. * known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage. * hemoptysis of red blood in excess of 2.5 ml (or one half teaspoon) within 8 weeks of first dose of study drug. * any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent/assent, or compliance to study procedures. * unable or unwilling to discontinue use of prohibited medications 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 treatment. * radiation therapy, minor surgery, tumor embolization, chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days prior to the protocol-mandated 4-week drug holiday. * administration of any non-oncologic investigational drug within 30 days or five half-lives (whichever is longer) prior to the protocol-mandated 4-week drug holiday. * any ongoing toxicity from prior anti-cancer therapy that is \> grade 1 and/or that is progressing in severity, except alopecia. * known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or excipients that contraindicates participation. * an untreated tumor growth rate of \< 6.1% during the screening period may exclude some patients.