Cholangiocarcinoma, Soft-tissue Sarcoma, Solid Tumors, Thyroid Cancer
Conditions
Brief summary
The purpose of this study is to determine the safety and toxicity of the combination of pazopanib and GSK1120212 in patients with solid tumors and identify the maximum tolerated dose (MTD) of this combination for phase II study.
Interventions
DRUGPazopanib
DRUGGSK1120212
Sponsors
National Comprehensive Cancer Network
Novartis
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD) of pazopanib and GSK1120212 when combined in patients with solid tumors | Approximately one year |
| Adverse events as a measure of the safety and tolerability profile of pazopanib in combination with GSK1120212 in patients with solid tumors | Approximately two years |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate at six months in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at the MTD | Approximately one year |
| Progression-free survival (PFS) in patients with advanced thyroid cancer, soft tissue sarcoma and cholangiocarcinoma being treated at MTD. | Approximately one year |
| Correlation of PK data with radiographic response, PD markers, and the impact of tumor histologic subtype and tumor genotype on radiographic response for patients with advanced thyroid cancer | Approximately one year |
| PD marker analysis on peripheral blood mononuclear cells for patients with soft tissue sarcoma and cholangiocarcinoma | Approximately one year |
Countries
United States
Outcome results
None listed