Temsirolimus and Irinotecan for Treatment Resistant Patients With Metastatic Colorectal Cancer and KRAS Mutations

Inclusion Criteria: * Histologically verified colorectal adenocarcinomas * Age \> 18 years and \< 70 * Metastatic colorectal cancer refractory 5-FU, oxaliplatin and irinotecan containing treatment regimes * KRAS mutation detected by DxS kit in primary tumor or metastatic lesion. * Measurable disease according to RECIST * ECOG performance status 0, 1 or 2 * Adequate renal, hepatic and haematological function * Normal serum cholesterol and triglycerides * Blood samples and available paraffin embedded tumor material for translational research studies * Fertile males and females (\< 2 years after last period for women) must use effective birth control * Signed Informed consent Exclusion Criteria: * Clinically significant heart disease, active severe infections or other concurrent disease * Other malignant diseases within 5 years of inclusion in the study, except basal cell squamous cell carcinoma of the skin and cervical carcinoma-in-situ * Prior radiotherapy within 30 days of treatment start * Other experimental therapy within 30 days of treatment initiation * Patients who are breast feeding, childbearing or of childbearing potential without using dual effective contraception * Clinical or radiological evidence of CNS metastasis * Completed any major surgery, excision biopsy or significant traumatic lesion ≥ 4 weeks from start of treatment and completed any minor surgery ≥ 1 week prior to start of treatment * Insertion of a vascular access device is not considered major or minor surgery from the viewpoint of protocol eligibility * Patients must have fully recovered from the procedure and have a fully healed incision * Planned radiation therapy against target-lesions * Patients with significant non-healing wounds or ulcers * History or evidence of thrombotic or hemorrhagic disorders * Significant haemorrhage (\> 30 ml/bleeding episode in previous 3 months) * Haemoptysis (\> 5 ml fresh blood in previous 4 weeks) * Patients on full-dose anticoagulation (e.g., warfarin) are eligible provided that both of the following criteria are met: * The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or is on a stable dose of low molecular weight heparin * The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices) * Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub-Arachnoid Hemorrhage (SAH) within 12 months prior to randomization * No known or history of HIV seropositivity * The use of ACE inhibitors is not permitted during the study * Known allergy to temsirolimus, sirolimus, polysorbate 80 or included agents. * Agents with strong CYP3A4-inhibitory potential