A Phase II Study of Pazopanib in the Treatment of Osteosarcoma Metastatic to the Lung
- 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
- ECOG performance status of 0-2
- Measurable disease per RECIST version 1.1 guidelines. At least one measurable lesion
must be in the lungs.
- Eligible subjects are required to have > 1 line of multi-agent chemotherapy either
neoadjuvantly or adjuvantly. Subjects may have had 0-2 lines of therapy for
- Measured cardiac ejection fraction > 50% or the institutional LLN 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.
- Children in care.
- Prior exposure to VEGFR tyrosine kinase inhibitor (small molecule or antibody) or
- 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 (CNS) metastases or
- Clinically significant gastrointestinal abnormalities that may increase the risk for
- Clinically significant gastrointestinal abnormalities that may affect absorption of
- 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
- 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 in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of
- 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.
- An untreated tumor growth rate of < 6.1% during the Screening period may exclude some