Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Man or woman at least 18 years old
Capable of understanding, signing and dating an informed consent approved by an Independent Ethics Committee (IEC)
Histologically confirmed adenocarcinoma of the colon or rectum in patients with initially unresectable metastatic (M1) disease
Wild-type RAS tumour status confirmed before study inclusion at local institution
Patients who have a treatment plan based on FOLFOX + anti-EGFR or FOLFIRI + anti-EGFR, as first-line treatment of mCRC
Eastern Cooperative Oncology Group (ECOG) performance status ≤2
Adequate bone marrow function: neutrophils ≥1.5 x109/L; platelets ≥100 x109/L; haemoglobin ≥9 g/dL
Hepatic, renal and metabolic function as follows: Total bilirubin count ≤1.5 x upper limit of normal (ULN), Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) <5 x ULN; Renal function, calculated as creatinine clearance or 24-hour creatinine clearance ≥50 mL/min; Magnesium > lower limit of normal (LLN)

Exclusion Criteria:

History of prior or concurrent central nervous system (CNS) metastases
History of another primary cancer, except: curatively treated in situ cervical cancer, or curatively resected non-melanoma skin cancer, or other primary solid tumour curatively treated with no known active disease present and no treatment administered for ≥5 years before treatment initiation
Known hypersensitivity to tetracyclines
Prior chemotherapy or other systemic anticancer therapy for treatment of metastatic colorectal carcinoma
Prior adjuvant chemotherapy for colorectal cancer terminated less than 6 months before metastatic disease was diagnosed
Unresolved toxicities of a previous systemic treatment that, in the opinion of the investigator, cause the patient unfit for inclusion
Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (e.g., cetuximab), antivascular endothelial growth factor (VEGF) or treatment with small molecule EGFR inhibitors (e.g., erlotinib)
Prior hormonal therapy, immunotherapy or approved or experimental antibody/proteins ≤30 days before inclusion.
Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia
History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computed tomography (CT)
Treatment for systemic infection within 14 days before the start of study treatment
Acute or subacute intestinal occlusion and/or active inflammatory bowel disease or other bowel disease that causes chronic diarrhoea (defined as grade ≥ 2 diarrhoea according to Common Terminology Criteria for Adverse Events (CTCAE)
Clinically significant peripheral sensory neuropathy
Evidence of previous acute hypersensitivity reaction, of any grade, to any component of the treatment
History of Gilbert disease or known dihydropyrimidine deficiency syndrome
Recent gastroduodenal ulcer to be active or uncontrolled
Recent pulmonary embolism, deep vein thrombosis, or other significant venous event
Pre-existing bleeding diathesis and/or coagulopathy with exception of well-controlled anticoagulation therapy
Recent major surgical procedure, open biopsy, or significant traumatic injury not yet recovered from prior major surgery
History of any disease that may increase the risks associated with study participation or may interfere with the interpretation of study results.
Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
Any disorder that compromises the patient's ability to provide written informed consent and/or comply with study procedures
Any investigational agent within 30 days prior to inclusion
Pregnant or breastfeeding woman
Surgery (excluding diagnostic biopsy or placement of a central venous catheter) and/or radiotherapy within 28 days prior to inclusion in the study.
Male or female of childbearing age who do not agree with taking adequate contraceptive precautions, i.e. use contraception double barrier (e.g. diaphragm plus condoms) or abstinence during the course of the study and for 6 months after the last administration of study drug for women and 1 month for men
The patient is unwilling or unable to meet the requirements of the study. Psychological, geographical, familial or sociological conditions that potentially prevent compliance with the study protocol and follow-up schedule. These conditions should be discussed with the patient before inclusion in the trial.