Study of Pazopanib in the Treatment of Surgically 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.

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.