First-line mCapOX+Cetuximab vs. mFOLFOX6+Cetuximab for Metastatic Left-sided CRC With Wild-type RAS/BRAF Genes

Study Overview
=================
Brief Summary
-----------------
This prospective, randomized, phase 2 study is conducted to evaluate the efficacy and safety of first line mCapOX plus cetuximab versus mFOLFOX6 plus cetuximab for metastatic left-sided CRC patients with wild-type RAS and BRAF genes.

Detailed Description
-----------------
The patients, who meet the inclusion criteria and have signed the informed consent, will be randomly assigned (1:1 ratio) to receive mCapOX plus cetuximab regimen (arm A) and mFOLFOX6 plus cetuximab regimen (arm B).

Official Title
-----------------
First-line Treatment of mCapOX Plus Cetuximab Versus mFOLFOX6 Plus Cetuximab for Metastatic Left-sided CRC Patients With Wild-type RAS/BRAF Genes: a Multicenter, Randomised, Phase 2 Study

Conditions
-----------------
Colo-rectal Cancer, Capecitabine, Cetuximab

Intervention / Treatment
-----------------
* Drug: mCapOX plus cetuximab
* Drug: mFOLFOX6 plus cetuximab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Able to provide written informed consent and can understand and comply with the requirements of the study; Men and women ≥ 18 years of age; Patients with histologically or cytologically confirmed metastatic left-sided colorectal adenocarcinoma with wild-type RAS and BRAF genes; Presence of at least one evaluable lesion, as defined in RECIST Version 1.1; With an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1; No palliative first-line chemotherapy, targeted, immunotherapy, or prior platinum-based adjuvant chemotherapy, relapse more than 12 months from the end of adjuvant chemotherapy; According to the imaging findings and surgical assessment of initial unresectable, synchronous metastatic colorectal cancer, no serious complications of the primary tumor (obstruction, perforation, massive hemorrhage that cannot be treated in internal medicine, etc.) ; Life expectancy of longer than 3 months ( clinical assessment); Requirements for lab indicators neutrophils ≥ 1.5 × 109/L, platelets ≥ 75 × 109/L, hemoglobin ≥ 8 g/dL, total bilirubin ≤ 1.5 × upper limit of normal (UNL); ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 × UNL (≤ 5 × UNL if liver metastases); alkaline phosphatase ≤ 2.5 × UNL (≤ 5 × UNL if liver metastases, ≤ 10 × UNL if bone metastases); LDH < 1500 U/L; creatinine clearance (calculated according to Cockcroft and Gault formula) > 50 mL/min or serum creatinine ≤ 1.5 × UNL; Exclusion Criteria: Patients with mCRC who were initially resectable with R0 resection or radiofrequency or SBRT were excluded. Patients diagnosed with MSI-H or dMMR by PCR or immunohistochemistry Hypersensitivity to any therapeutic agent. Patients who received adjuvant chemotherapy containing oxaliplatin and fluorouracil within 12 months before entering the study; Patients who have failed one or more palliative chemotherapy regimens; Patients with uncontrolled hepatitis B virus Peripheral neuropathy ≥ CTC grade 2; Neurological or psychiatric disorders affecting cognitive performance; Patients with central nervous system metastasis could not be controlled with radiotherapy; Previous enteritis, chronic diarrhea, or recurrent bowel obstruction; uncontrolled bleeding from internal medicine; bowel perforation Uncontrolled concomitant diseases within 6 months before the study, including unstable angina, acute myocardial infarction, cerebrovascular accident, etc.; Pregnant or lactating patients, or those of childbearing potential who do not take adequate contraceptive measures; History of other malignancies, but no disease-free survival longer than 5 years; Patients concurrently receiving other anti-tumor treatment or participating in other interventional clinical trials; Patients who are unable to comply with this study for psychological, family or social reasons. Patients with other serious diseases that the investigator considers not suitable.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>mCapOX (capecitabine+oxaliplatin) plus cetuximab | Drug: mCapOX plus cetuximab<br>* capecitabine 1000mg/m2 po bid d1-7+oxaliplatin ivgtt 85mg/m2 d1+cetuximab ivgtt 500mg/m2, q2w<br>|
| Active Comparator: Arm B<br>mFOLFOX6 (fluorouracil+leucovorin+oxaliplatin) plus cetuximab | Drug: mFOLFOX6 plus cetuximab<br>* oxaliplatin ivgtt 85mg/m2 d1+ leucovorin ivgtt 400mg/m2 d1+ fluorouracil iv bolus 400mg/m2 d1+ fluorouracil 2400mg/m2 continuous infusion for 46h+cetuximab ivgtt 500mg/m2, q2w<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Progression free survival is defined as the period from randomization to disease progress or death. | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | The rate of complete response and partial response | 6 months | 
| Disease control rate | The rate of complete response, partial response and stable disease. | 6 months | 
| Overall survival | Overall survial is defined as the period from randomization to death. | up to 4 years | 
| Adverse event rate | The rate of adverse event after treatment | 3 years |