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

Phase II Study of Pemetrexed and Gemcitabine for Treatment Resistant Patients With Metastatic Colorectal Cancer and KRAS Mutations

This study aims to investigate the efficacy and safety of the combination of pemetrexed and gemcitabine in heavily pre-treated, chemotherapy resistant colorectal cancer patients with 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.