A Phase I/II Study of XELOXIRI and Bevacizumab as First-line Treatment in Metastatic Colorectal Cancer

Inclusion Criteria:

* Patients with histologically confirmed metastatic colorectal adenocarcinoma;
* Age 18-80 years old;
* Eastern Cooperation Oncology Group (ECOG) performance score(\<2);
* At least one measurable lesion for disease assessment according to RECIST version 1.1;
* Able to take oral medications;
* Previous fluoropyrimidine-based adjuvant or neoadjuvant chemotherapy was allowed only when it ended ≥ 6 months before study enrollment;
* No previous therapy for mCRC;
* Adequate organ functions as assessed by the following laboratory requirements: Leukocytes≥3.0x109/L, absolute neutrophil count≥1.5x109/L, platelet count≥100x109/L, hemoglobin≥9g/dL; serum bilirubin≤1.5x the upper limit of normal(ULN);Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)≤3x ULN; serum creatinine≤1.5x ULN; calculated creatinine clearance or 24 hour creatinine clearance ≥60ml/min.
* An expected survival of at least 3 months;
* Willingly provide written informed consent to study procedures.

Exclusion Criteria:

* Patients with dysphagia, active peptic ulcer, intestinal obstruction, active gastrointestinal bleeding, peptic perforation, malabsorption syndrome or uncontrolled intestinal inflammatory diseases;
* With a history of extensive enterotomy or pelvic radiation therapy; Suffering from grade 2 or higher symptomatic peripheral neuropathy according to National Cancer Institute Common Toxicity (NCI-CTC) criteria;
* Uncontrolled central nervous system metastasis, disseminated intravascular coagulation or active infection;
* With concurrent cancer distinct from colorectal adenocarcinoma except cured skin basal cell carcinoma and cervical carcinoma in situ;
* Undergone a major operation, open biopsy or major traumatic injury within 28 days before study enrollment or have potential to receive major operation during the trial;
* Received central venous access device within 2 days before study enrollment;
* Any kind of concurrent cardiac disease with clinical meanings, such as cardiovascular accident, myocardial infarction, thromboembolism or hemorrhage within 6 months before enrollment, congestive heart failure ≤New York Heart Association (NYHA) class 2 or uncontrolled hypertension.
* With positive urine protein and 24-hour urinary protein content\>1g;
* Have a tendency of bleeding or clotting;
* With nasty open wounds, ulcers or fractures;
* Current or recent treatment of anticoagulants, antiplatelet agent or nonsteroidal anti-inflammatory drugs, while aspirin of daily dose less than 325mg is allowed.
* With any illness or medical conditions that may jeopardize the patient's compliance or interfere the analyses or judgements of study results;
* Pregnancy or lactation at the time of study entry;
* With fertility but refuse to contraception.