Efficacy and Safety of the Prophylactic Use of Doxycycline +/- Vitamin K Cream

Inclusion Criteria:

* Written informed consent must be given
* Patient ≥ 18 years
* Histologically proven and measurable metastatic adenocarcinoma of the colon or rectum (according to modified RECIST criteria v.1.1)
* Patients eligible for Erbitux and FOLFIRI treatment K-Ras wild type tumour
* Metastatic disease
* Life expectancy of at least 12 weeks
* WHO performance status of 0 or 1
* Effective contraception for both male and female patients if the risk of conception exists
* Adequate organ function
* Adequate bone marrow, hepatic and renal function (Hemoglobin \> 10.0 g/dL, platelet count \> 100 x 109/L, absolute neutrophil count \> 1.5 x 109/L; ALAT, ASAT \< 2.5 x ULN (upper limit of normal range) or \< 5x ULN in case of liver metastasis; Alkaline phosphatase \< 2.5 x ULN; Total bilirubin \< 1.5 x ULN; Creatinine clearance \> 50 mL/min (calculated according to Cockcroft and Gault formula)).

Exclusion Criteria:

* Prior treatment for metastatic disease (adjuvant therapy with 5-FU/oxaliplatin based regimens) allowed if stopped 6 months prior to registration on study
* Prior treatment with EGFR inhibitor
* Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to study entry
* Administration of any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment with study drugs
* Concurrent chronic systemic immune therapy, chemotherapy, radiation therapy or hormone therapy not indicated in the study protocol
* Any active dermatological condition \> grade 1 at baseline possibly interfering with or influencing the results or conduct of the present study
* Brain metastasis (known or suspected)
* Significant impairment of intestinal resorption (e.g. chronic diarrhea, inflammatory bowel disease)
* Any other uncontrolled concomitant illness, including serious uncontrolled intercurrent infection
* Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias)
* Known allergy or any other adverse reaction to any of the study drugs or to any related compound.
* Any organ allograft requiring immunosuppressive therapy.
* Pregnancy (absence to be confirmed by serum/urine beta human chorion gonadotrophin (HCG)) or breast-feeding.
* Other previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix surgically cured or adequately treated.
* Known drug abuse / alcohol abuse
* Legal incapacity or limited legal capacity
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and followup schedule; those conditions should be discussed with the patient before registration in the trial.
* Medical or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or meaningfully sign informed consent.
* Known M. Meulengracht (Gilbert´s disease) or DPD-insufficiency
* Known coagulation disorders
* Ongoing or planned treatment with coumarin derivates