Pemetrexed and Gemcitabine for Treatment Resistant Patients With Metastatic Colorectal Cancer and KRAS Mutations

Inclusion Criteria: * Histologically verified adenocarcinoma in colon or rectum * Age \>18 * Metastatic colorectal cancer progressed after chemotherapy regimens containing fluoropyrimidines, oxaliplatin and irinotecan. * KRAS mutation in primary tumour or metastasis. * Measurable disease according to RECIST * ECOG performance status 0, 1 or 2 * Adequate function of liver, kidneys and bone marrow measured by biochemistry (max. 2 weeks before enrolment) * EDTA clearance: Uncorrected GFR \> 45 ml/min. * Neutrophilocytes ≥1.5 x 10\^9/l, leukocytes ≥3.0 x 10\^9/l, thrombocytes ≥100x10\^9/l * ALAT ≤ 3 x upper normal value (ULN), bilirubin ≤ 3 x upper normal value, Aptt and INR normal (or 2-3 at AC treatment). (ALAT and basic phosphatase ≤ 5 x upper normal value in case of liver metastases). * Blood samples and paraffin embedded tissue from primary tumour and/or metastases for translational research. * Fertile men and women (women \<2 year after last menstruation) must use efficient birth control. * Signed informed consent. Exclusion Criteria: * Clinically significant other concurrent disease making the patient unfit for participation in the study according to the investigator. * Other malignant disease within 5 years prior to study enrolment, except from planocellular and basal cell carcinomas in the skin or carcinoma-in-situ cervix. * Other experimental treatment within 30 days prior to treatment start. * Pregnant or breastfeeding women. * Clinical or radiological signs of CNS metastases. * Planned radiation of target lesions. * Concurrent vaccination against yellow fever.