efficacy and safety of the prophylactic use of doxycycline +/- vitamin k cream

Conditions: Metastatic Colorectal Cancer

Summary: the aim of this phase 2, two-arm, randomized, double blind placebo controlled study is to evaluate the efficacy of combination therapy of doxycycline and vitamin k1 compared to doxycycline plus placebo for the prevention of acne-like skin rash in mcrc patients receiving first line cetuximab treatment.

the aim of this phase 2, two-arm, randomized, double blind placebo controlled study is to evaluate the efficacy of combination therapy of doxycycline and vitamin k1 compared to doxycycline plus placebo for the prevention of acne-like skin rash in mcrc patients receiving first line cetuximab treatment.

Eligibility criteria:
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 \ 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