Phase 3 Study of Surgery Combined With Neoadjuvant Chemotherapy(XELOX) in Colorectal Cancer With Resectable Liver Metastasis

Study Overview
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Brief Summary
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This study aims to discuss the efficacy and safety of neoadjuvant chemotherapy with XELOX regimen (oxaliplatin plus capecitabine) .

Detailed Description
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Liver metastasis is the most important prognostic factor of colorectal cancer. Reasonable multidisciplinary therapy might improve the prognosis of patients with liver metastasis. Surgery has been the first choice under such situation. Recently, neoadjuvant chemotherapy has also shown its value in unresectable liver metastasis, for it can increase the chance of R0 resection and give some clues to chemosensitivity of agents. However, for those resectable lesions, the role and safety of neoadjuvant chemotherapy has yet to be confirmed. so we design this study.

Official Title
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A Phase III Study of Surgery in Combination With Neoadjuvant Chemotherapy of Oxaliplatin Plus Capecitabine in Colorectal Cancer With Respectable Liver Metastasis

Conditions
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Colorectal Cancer, Resectable Liver Metastasis

Intervention / Treatment
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* Drug: neoadjuvant chemotherapy with oxaliplatin and capecitabine
* Procedure: resection of liver metastasis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed colorectal cancer with liver metastasis(all patients should have the pathological report of colorectal cancer. The chances of hepatocellular carcinoma or metastasis from other primary lesions should be excluded. ) Liver metastasis should be resected with R0 resection and to save enough normal liver tissue Anticipated liver resection: for normal liver, ﹤70%; for liver with cirrhosis, ﹤50% No metastasis of other organs or lymph nodes in abdominal cavity No previous use of oxaliplatin and capecitabine, or previous adjuvant treatment ended more than 6 months Age 18 to 75 years old Karnofsky performance status ≥70 Life expectancy of ≥3 month Bilirubin level < 1.5mg/dL Serum creatinine <1.0 times ULN Absolute neutrophil count ≥2000/mm3, platelet>100,000/mm3, Hb>9g/dl Having signed informed consent Exclusion Criteria: previous use of oxaliplatin or fluorouracil-based chemotherapy in 6 months. No R0 resection or not enough normal liver tissue left previous radiotherapy of target lesions accompanied with unresectable other metastasis or malignant pleural fluids or ascites. complete or uncompleted liver obstruction peripheral neuropathy(NCI-CTC grade 1 or more) mental disturbance neuropathy that influence the cognition, including brain metastasis other serious disease such as uncontrollable active infection, heart infarction with 1 year, un controlled hypertension, arrhythmia with high risk, or unstable heart infarction,heart failure, coronary artery disease, myocardial infarction within the last 6 months Other previous malignancy within 5 year, except non-melanoma skin cancer accompany with other anti-tumor therapies,including immune therapy, intervention or injection with chemotherapeutical agents into serous cavity, or participating other clinical trials. Pregnancy or lactation period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>2 3 cycles of neoadjuvant chemotherapy before resection of liver metastasis | Drug: neoadjuvant chemotherapy with oxaliplatin and capecitabine<br>* oxaliplatin: 130mg/m2, d1(Q3w) capecitabine:1000mg/m2 bid, d1-14(Q3w)<br>Procedure: resection of liver metastasis<br>* surgery with the aim of R0 resection<br>|
| Active Comparator: 2<br>no neoadjuvant chemotherapy, resect the liver metastasis directly | Procedure: resection of liver metastasis<br>* surgery with the aim of R0 resection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease free survival rate |  | 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate |  | at the time of pathological report | 
| survival rate and over survival |  | 5 year | 
| surgery related mortality |  | peri-operation period | 
| response rate and safety of XELOX as a neoadjuvant regimen |  | no time frame |