This is a phase 2 study (the second phase in testing a new drug or drug combination) to see how useful the combination of two drugs, panitumumab and trametinib, are in patients with advanced colorectal cancer with KRAS, NRAS, or BRAF wild type (genes that are not mutated).

Panitumumab is a drug that is approved by Health Canada for the treatment of advanced colorectal cancer with KRAS wild type. Panitumumab works by binding to and blocking the protein, epidermal growth factor receptor (EGFR) from working.

Trametinib is a drug that is approved by Health Canada for the treatment of melanoma with a mutation in the BRAF gene. Trametinib works by binding to and blocking mitogen-activated protein kinase kinase (MEK) 1 and MEK2 from working.

Previous studies have shown that the combination of panitumumab and trametinib may be more useful in KRAS, NRAS, or BRAF wild type colorectal cancer.

Inclusion Criteria:

• 18 years of age or older
• KRAS/NRAS/BRAF wild type colorectal cancer, not responsive to standard therapies, no approved or curative therapy, refuse standard therapy
• Prior 5-FU, oxaliplatin and irinotecan
• ECOG Performance Status of 0 or 1
• Able to swallow/retain oral drugs
• Able and agree to have provide tumor tissue/have biopsies
• Agree to use contraception
• Not pregnant
• Adequate organ system function

Exclusion Criteria:

• Chemotherapy, radiotherapy, immunotherapy, or other anti-cancer therapies <28 days or 5 half lives
• Prior EGFR, MEK, or RAF inhibitor or regorafenib
• Current use of prohibited medications
• Unresolved side effects
• GI disease or other condition affecting GI absorption
• Mucosal or internal bleeding
• Any major surgery \