BRAF/MEK/EGFR Inhibitor Combination Study in Colorectal Cancer (CRC)
Active, not recruiting
This is an open-label, four-part Phase I/II study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of trametinib (GSK1120212) and dabrafenib (GSK2118436) when administered in combination with the anti-EGFR antibody panitumumab in subjects with BRAF-mutation V600E positive colorectal cancer (CRC) and in subjects with CRC with secondary resistance to prior anti-EGFR therapy. Part 1 of the study will consist of dose-escalation cohorts, following a 3 + 3 enrollment scheme. Part 2 of the study will consist of expansion cohorts to investigate safety and clinical activity of dabrafenib in combination with panitumumab and trametinib plus dabrafenib in combination with panitumumab. Part 3 of the study will be a randomized Phase II study comparing dosing with dabrafenib in combination with panitumumab and trametinib plus dabrafenib in combination with panitumumab as compared to the chemotherapy comparator (a regimen of leucovorin calcium, fluorouracil, oxaliplatin (FOLFOX), leucovorin calcium, fluorouracil, irinotecan hydrochloride (FOLFIRI) or irinotecan with or without panitumumab or bevacizumab). Subjects will be assigned to treatment groups in a randomized fashion to compare safety and clinical activity. Part 4 of the study will investigate the trametinib/panitumumab combination, including dose escalation and subsequent cohort expansion in two patient populations: 1) BRAF-mutation V600E positive CRC and 2) subjects with CRC who developed secondary resistance to prior anti-EGFR therapy. The objective of Part 4 is to identify the recommended Phase 2 dose/regimen for trametinib dosed in combination with panitumumab in dose escalation and to identify an initial signal of clinical activity in expansion cohorts.