A Phase II Study of Pazopanib in the Treatment of Surgically Unresectable or Metastatic Liposarcoma
- 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
- 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.
- 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
- History or clinical evidence of central nervous system metastases or leptomeningeal
- Clinically significant gastrointestinal (GI) abnormalities that may increase the risk
for GI bleeding.
- Clinically significant GI abnormalities that may affect absorption of investigational
- 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.