Safety Study of the Combination of Panitumumab, Irinotecan and Everolimus in the Treatment of Advanced Colorectal Cancer

Inclusion Criteria: * Age \> 18 years * Histological diagnosis of colorectal cancer that is KRAS wild type * Metastatic disease not amenable to resection * Measurable disease as assessed by CT scan using RECIST criteria * Received and failed fluoropyrimidine therapy * Radiographically documented disease progression per RECIST criteria * For phase 1b group only, ECOG PS 0-1 * For phase 2 group only, ECOG PS 0-2 * Adequate bone marrow function with haemoglobin \> 100 g/L, platelets \> 100 X 109/l; neutrophils \> 1.5 X 109/l within 7 days of enrolment * Adequate renal function, with calculated creatinine clearance \>40 ml/min (Cockcroft and Gault) within 7 days of enrolment * Adequate hepatic function with serum total bilirubin \< 1.25 X upper limit of normal range and ALT or AST\<2.5xULN (\<5xULN if liver metastases present) within 7 days of enrolment * Magnesium ≥ lower limit of normal within 7 days of enrolment. * Fasting serum cholesterol ≤ 7.75mmol/L AND fasting triglycerides ≤ 2.5 x ULN. Note: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. * Life expectancy of at least 12 weeks * Negative pregnancy test ≤ 72 hours before commencing study treatment (women of childbearing potential only). * Written informed consent including consent for biomarker studies Exclusion Criteria: * Presence of KRAS mutation in tumour sample * For Phase 1b group only, patients with prior pelvic radiotherapy. * Systemic chemotherapy, immunotherapy, approved proteins/antibodies or any investigational agent within 4 weeks prior to commencing study treatment * Radiotherapy within 14 days of commencing study treatment. * Unresolved toxicities from prior systemic therapy or radiotherapy * Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol * Prior treatment with drugs targeting EGFR such as cetuximab, panitumumab or erlotinib * Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus) * Prior therapy with irinotecan * CYP3A4 enzyme inducing anti-convulsant medication ≤ 14 days prior to study treatment. * Ketoconazole ≤ 7 days before study treatment. * Uncontrolled diabetes mellitus defined by fasting glucose \>1.5 x ULN. * Known cirrhosis, chronic active hepatitis, or chronic persistent hepatitis * Patients with known interstitial lung disease or severely impaired lung function * Patients with active bleeding diatheses. * Any uncontrolled clinically significant cardiac disease, arrhythmias or angina pectoris * Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea * Chronic treatment with immunosuppressives * Patients with a known history of HIV seropositivity * Patients who have any severe and/or uncontrolled medical conditions or infections * Untreated or symptomatic CNS metastases * Patients who have a history of another primary malignant disease * Pregnancy or lactation. * Women and partners of women of childbearing potential who are not using effective contraception.