A 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.
To help us best learn how to use new drugs that may be effective treatments for cancer; Evaluate the safety and tolerability of the combination of pazopanib and GSK120210 in patients with solid tumors and advanced thyroid cancer; determine the maximum tolerated dose; to explore the correlation of PK data with radiographic response; explore the impact of tumor histologic subtype and the tumor genotype on radiographic response.
- dose escalation cohort: advanced solid tumor that is refractory to standard treatment - dose expansion cohort: advanced, inoperable differentiated thyroid cancer (DTC) with disease progression within 6 months of enrolling in the study. Disease must have radioiodine non-avid lesions, OR with radioiodine avid lesions that have not responded to iodine greater than 6 months prior to enrollment. - measurable disease - good performance status - be able to swallow pills - be able to give informed consent, - good organ and blood functions - BP less than 140/90 - QTc less than 480 msec - treated brain metastasis, stable for at least 8 weeks and off glucocorticoids - no treatment with known strong substrates or inhibitors of CYP3A enzymes - no history of retinal vein occlusion or central serous retinopathy
Outpatient regimen of two oral medications delivered daily during 28-day cycles. Subjects self administer Pazopanib and GSK1120212 tablets on an empty stomach. Subjects fast, except for water, for one hour before or two hours after a meal. Treatment continues until intolerable toxicity or disease progresses. Dose escalating cohorts continue until the maximally tolerated dose (MTD) and dose limiting toxicities (DLTs) are determined. Subjects are seen and assessed on D1 of each treatment cycle and monitored midcycle for labs. EKGs are done prior to every other treatment cycle. and during first cycle then once during each cycle of treatment. Radiologic measurements are to be done every 8 weeks.
04/25/2014 04:02 AM