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 of tumor tissue;
* Patients have measurable disease as defined by RECIST 1.1 as determined by investigator;
* Patient with a history of radiotherapy at least 3 months before on the day of providing consent, but the measurable lesion should not be within the scope of radiotherapy;
* 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 Oncology Group.；
* Patients with Life expectancy of more than 12 weeks;
* Patients must have the ability to understand and sign the written informed consent voluntarily;
* Female of childbearing potential who are negative in a pregnancy test within 14 days before enrollment. Both male and female patients should agree to use an adequate method of contraception (total abstinence, an intrauterine device or hormone releasing system, an contraceptive implant and an oral contraceptive) starting with the first dose of study therapy through 120 days after the last dose of study therapy. Duration will 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 first medication;
* 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 chemotherapy as 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 liver metastases; (5.0-times the upper limit of normal for patients without liver metastases)
  * Creatinine \>1.5-times the upper limit of normal；
* Patients with cancers other than advanced colorectal cancer within five years prior to the start of treatment in this study. Cervical carcinoma in situ, cured basal cell carcinoma and bladder epithelial tumor were excluded;；
* Patients without legal capacity or limited civil capacity;