A Double Blind Placebo Controlled Randomized Phase II Study Evaluating the Efficacy and Safety of the Prophylactic Use of Doxycycline +/- Vitamin K Cream in First Line mCRC Patients Treated With Erbitux and FOLFIRI.
- 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
- 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)).
- 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
- 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
- Any other uncontrolled concomitant illness, including serious uncontrolled
- 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
- 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