induction chemoterapy with folfoxiri plus cetuxumab in unresectable colorectal cancer patient

Conditions: Metastatic Colorectal Cancer

Summary: this is a phase ii randomized study of 4-months induction first-line chemotherapy with folfoxiri + cetuximab followed by maintenance with cetuximab or bevacizumab in patients affected by kras wild type (wt) mcrc.

the aim of the study is to obtain a rapid disease control with the therapy and the maximum tumoral shrinkage, and than to treat patient with less intensive maintenance to inhibit tumoral regrowth.

Eligibility criteria:
inclusion criteria: * histologically confirmed colorectal adenocarcinoma; * availability of formalin-fixed paraffin embedded tumor block from primary and/or metastasis; * kras wild-type status of primary colorectal cancer or related metastasis; * unresectable and measurable metastatic disease according to recist criteria; * male or female, aged \> 18 years and \< 75 years; * ecog ps \< 2 if aged \< 71 years, ecog ps = 0 if aged 71-75 years; * life expectancy of more than 3 months; * adequate haematological function: anc ≥ 1.5 x 109/l; platelets ≥ 100 x 109/l, hb ≥ 9 g/dl; * adequate liver and renal function: serum bilirubin ≤ 1.5 x uln; alkaline phosphatase and transaminases ≤ 2.5 x uln (in case of liver metastases \< 5 x uln); serum creatinine ≤ 1.5 x uln; * previous adjuvant chemotherapy containing oxaliplatin is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse; * previous adjuvant chemotherapy with fluoropyrimidine monotherapy is allowed if more than 6 months have elapsed between the end of adjuvant and first relapse; * at least 6 weeks from prior extended radiotherapy and 4 weeks from surgery; * written informed consent to experimental treatment and kras analysis. exclusion criteria: * prior palliative chemotherapy; * prior treatment with egfr or vegf inhibitors; * symptomatic peripheral neuropathy \> 2 grade ncic-ctg criteria; * presence or history of cns metastasis; * active uncontrolled infections; active disseminated intravascular coagulation; * past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix; * clinically significant cardiovascular disease: cerebrovascular accidents or myocardial infarction ≤ 12 months before treatment start, unstable angina, nyha ≥ grade 2 chronic heart failure, uncontrolled arrhythmia, uncontrolled hypertension; * serious, non-healing wound, ulcer, or bone fracture; * evidence of bleeding diathesis or coagulopathy; * major surgical procedure or significant traumatic injury within 28 days prior to study treatment start; * current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes or chronic, daily treatment with high-dose aspirin (\>325 mg/day); * subtotal colectomy, malabsorption syndrome and chronic inflammatory bowel disease (i.e. ulcerative colitis, chron syndrome); * fertile women (\<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception. * psychiatric disorder precluding understanding of information on trial related topics, * serious underlying medical condition (judged by the investigator) which could impair the ability of the patient to participate in the trial (e.g. uncontrolled diabetes mellitus, active autoimmune disease) * concurrent treatment with other experimental drugs or other anti-cancer therapy; treatment in a clinical trial within 30 days prior to trial entry * definite contraindications for the use of corticosteroids and antihistamines as premedication * known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs * any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies * pregnancy * any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up 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 sign meaningful informed consent

Keywords: colorectal cancer, bevacizumab cetuximab folfoxiri kras wild type