Phase I Study Determining the Safety and Tolerability of Combination Therapy With Pazopanib, a VEGFR/PDGFR/Raf Inhibitor, and GSK1120212, a MEK Inhibitor, in Advanced Solid Tumors Enriched With Patients With Advanced Differentiated Thyroid Cancer, Soft Tissue Sarcoma, and Cholangiocarcinoma
- Dose escalation cohort for all solid tumors is complete and closed to enrollment. For
the expansion cohorts, patients must have: advanced, inoperable differentiated
thyroid cancer (DTC), soft-tissue sarcoma or cholangiocarcinoma. 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.
- Chemotherapy, radiotherapy, other investigational therapy, or major surgery within 4
- 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
- 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.