Induction Chemoterapy With Folfoxiri Plus Cetuxumab in Unresectable Colorectal Cancer Patient (MACBETH)

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring colorectal cancer,, bevacizumab, cetuximab, folfoxiri, kras wild type Read More

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