study of pazopanib in the treatment of surgically unresectable or metastatic liposarcoma

Conditions: Liposarcoma; Surgically Unresectable Liposarcoma; Metastatic Liposarcoma

Summary: the purpose of this study is to evaluate the effectiveness and safety of single agent pazopanib in subjects with unresectable or metastatic liposarcoma.

this is a phase ii, multicenter, prospective, open label, single arm study. the primary endpoint of the study is progression-free rate as defined by response evaluation criteria in solid tumors (recist) guidelines version 1.1 at week 12 after start of treatment. the secondary endpoints include overall progression-free survival (pfs), response rate (rr), duration of response, overall survival (os), and toxicity assessment through the reporting of adverse events.

Eligibility criteria:
inclusion criteria: * written informed consent. * age \> or = to 18 years. * histologically or cytologically confirmed high- or intermediate-grade liposarcoma (allowed subtypes include liposarcoma dedifferentiated, myxoid/round cell, pleomorphic, mixed-type, or not otherwise specified). * surgically unresectable or metastatic disease. * any number of prior treatment treatment regimens, including treatment naive subjects. * eastern cooperative oncology group (ecog) performance status of 0 or 1. * measurable or evaluable (non-measurable) disease per recist guidelines version 1.1. subjects must have documented disease progression within the past 6 months. * adequate organ system function determined within 14 days prior to first dose of study treatment. * left ventricular ejection fraction (lvef) \> 50% of the institutional lln within 28 days prior to the first dose of study treatment. * females must be of either non-child bearing potential or have a negative pregnancy test within 7 days prior to the first dose of study treatment. exclusion criteria: * well differentiated liposarcoma. * prior treatment with tyrosine kinase inhibitors (tkis) or vascular endothelial growth factor (vegf) inhibitors. * 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 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 (gi) abnormalities that may increase the risk for gi bleeding. * clinically significant gi abnormalities that may affect absorption of investigational product. * presence of uncontrolled infection. * corrected qt interval \> 480 msecs using bazett's formula. * history of certain cardiovascular conditions within the past 6 months. * poorly controlled hypertension \[defined as systolic blood pressure of \> or = 140 mmhg or diastolic blood pressure \> or = 90 mmhg\]. * history of cerebrovascular accident including transient ischemic attack, pulmonary embolism, or untreated deep vein thrombosis within the past 6 months. * prior major surgery or trauma within 28 days prior to the first dose of study drug 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 in excess of 2.5 ml 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, 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 study treatment. * radiation therapy, minor surgery, tumor embolization, 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 study drug. * administration of any non-oncologic investigational drug within 30 days or five half-lives (whichever is longer) prior to receiving the first dose of study drug. * 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 to idiosyncrasy to drugs chemically realted to pazopanib or excipients that contraindicates participation.

Keywords: liposarcoma