Cetuximab and Vemurafenib Plus FOLFIRI for BRAF V600E Mutated Advanced Colorectal Cancer (IMPROVEMENT)

Inclusion Criteria:

• Patients have histologically or cytologically confirmed advanced or recurrent CRC;
• Patients with BRAV V600E mutation/KRAS WT based on the NGS or ARMS-PCR detection oftumor tissue;
• Patients have measurable disease as defined by RECIST 1.1 as determined byinvestigator;
• Patient with a history of radiotherapy at least 3 months before on the day ofproviding consent, but the measurable lesion should not be within the scope ofradiotherapy;
• Patients without a history of receiving vemurafenib or cetuximab;
• Patients with age of 18-75yr;
• Patients with a performance status of 0,1or 2 on the Eastern Cooperative OncologyGroup.；
• Patients with Life expectancy of more than 12 weeks;
• Patients must have the ability to understand and sign the written informed consentvoluntarily;
• Female of childbearing potential who are negative in a pregnancy test within 14 daysbefore enrollment. Both male and female patients should agree to use an adequatemethod of contraception (total abstinence, an intrauterine device or hormone releasingsystem, an contraceptive implant and an oral contraceptive) starting with the firstdose of study therapy through 120 days after the last dose of study therapy. Durationwill be determined when the subject is assigned to treatment.

Exclusion Criteria:

• Patients with KRAS/NRAS mutation;
• Patients with major surgery or severe trauma within 4 weeks before the firstmedication;
• Patients with hypersensitivity to the components in the study protocol;；
• Patients who are ready to give birth or are pregnant.。
• Patients with brain metastases 。
• Bone marrow, liver and kidney function did not meet the requirements of chemotherapyas follows：
• Neutrophil count<1,500/mm3；
• Platelet count <80,000/mm3；
• Total bilirubin >1.5-times the upper limit of normal；
• ALT/AST>2.5-times the upper limit of normal for patients without livermetastases; (5.0-times the upper limit of normal for patients without livermetastases)
• Creatinine >1.5-times the upper limit of normal；
• Patients with cancers other than advanced colorectal cancer within five years prior tothe start of treatment in this study. Cervical carcinoma in situ, cured basal cellcarcinoma and bladder epithelial tumor were excluded;；
• Patients without legal capacity or limited civil capacity;