Colorectal Cancer colorectal cancer
Conditions
Interventions
Patients will be enrolled in two dosing groups:
* dabrafenib in combination with panitumumab
* trametinib in combination with dabrafenib and panitumumab
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * BRAF V600E mutation positive colorectal cancer (CRC), as determined by local genetic testing. * Provision of archival tissue; if archival tissue is not available or found to not contain tumor tissue, a fresh biopsy is required. * Willingness to follow contraception requirements. * ECOG 0 or 1. * LVEF *LLN, or 50% if not defined by institution. * Organ function as noted in Table 17: * ANC *1.2 × 109/L * Hemoglobin *9 g/dL or 5.6 mmol/L * Platelets *75 × 109/L * PT/INR and PTT *1.5 x ULN * Mg++ * LLN * Albumin *2.5 g/dL or 25 g/L * Total bilirubin *1.5 x ULN * Creatinine * 1.5 ULN or Calculated creatinine clearance * 50 mL/min
Exclusion criteria
Exclusion criteria: * Prior malignancy, other than colorectal cancer. * Prior exposure to BRAF or MEK inhibitors. * Part 2 ONLY* prior exposure to EGFR antibodies or inhibitors. * KRAS mutation positive. * Received an investigational or approved anti-cancer drug within 4 weeks, or within 5 half-lives (whichever is shorter) of the first dose of study drug(s). At least 14 days must have passed between the last dose of prior investigational agent and the first dose of study drug(s). * RVO, CSR or predisposing factors to RVO or CSR. Ophthalmic exam is required at screening, and intraocular pressure must not exceed 21mm Hg. * Brain mets must be stable *90 days and treated with surgery or stereotactic radiosurgery.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Part 1 secondary objectives: To describe the pharmacokinetics of dabrafenib, trametinib and panitumumab after combination therapy To determine preliminary clinical activity of dabrafenib dosed orally in combination with panitumumab To determine clinical activity of trametinib dosed orally in combination with dabrafenib and panitumumab Part 2 secondary objectives: To characterize the population PK parameters of dabrafenib and trametinib dosed orally in combination with anti-EGFR antibody (panitumumab) To characterize the durability of response with dabrafenib dosed orally in combination with panitumumab To characterize the durability of response with trametinib dosed orally in combination with dabrafenib and panitumumab | — |
Primary
| Measure | Time frame |
|---|---|
| Part 1 primary objectives: To determine the safety, tolerability and range of tolerated combination doses in subjects with BRAF-V600E mutation-positive CRC in two dosing groups: * dabrafenib dosed orally in combination with panitumumab * trametinib dosed orally in combination with dabrafenib and panitumumab Part 2 primary objectives: To determine the safety, tolerability and range of tolerated combination doses in subjects with BRAF-V600E mutation-positive CRC in two dosing groups: * dabrafenib dosed orally in combination with panitumumab * trametinib dosed orally in combination with dabrafenib and panitumumab | — |
Countries
Netherlands
Outcome results
None listed