Phase 1 Study of Pazopanib With GSK1120212 in Advanced Solid Tumors, Enriched With Patients With Differentiated Thyroid Cancer, Soft-tissue Sarcoma, and Cholangiocarcinoma

Inclusion Criteria:

• Dose escalation cohort for all solid tumors is closed to enrollment.
• Expansion cohorts: Soft-tissue sarcoma, cholangiocarcinoma, and differentiated thyroid cancer (DTC) cohorts are closed to enrollment. Patients in the DTC cohort must have disease that is able to be biopsied.
• Must have measurable disease.
• Tumor progression in the 6-month period prior to study drug initiation.
• DTC patients: must have radioiodine non-avid lesions, OR radioiodine avid lesions that have not responded to treatment with radioactive iodine.
• ECOG performance status less than or equal to 1.
• Life expectancy >3 months.
• Blood pressure <140 mmHg and <90 mmHg.
• LVEF is >= 50%
• Must be able to swallow pills.

Exclusion Criteria:

• Chemotherapy, radiotherapy, other investigational therapy, or major surgery within 4 weeks.
• Sarcoma and cholangiocarcinoma ONLY: Prior VEGF-targeted TKI therapy.
• Pregnant or currently breastfeeding.
• Unresolved toxicity greater than grade 1.
• Evidence of active hepatitis or HIV.
• Significant cardiovascular disease.
• Taking medications known to be strong inducers or inhibitors of CYP3A enzymes.
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.
• History of gastrointestinal condition causing malabsorption or obstruction.
• Cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep vein thrombosis (DVT) within past 6 months.
• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase risk of pulmonary hemorrhage.
• Hemoptysis within 6 months of starting treatment.
• History of retinal vein occlusion (RVO) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR as assessed by ophthalmic exam.
• Known brain mets that are not stable for at least 8 weeks prior to treatment, or patient is on glucocorticoids for brain mets.