Intra-operative Chemotherapy With 5-FU for Colorectal Cancer Patients Receiving Curative Resection: Efficacy and Safety

Study Overview
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Brief Summary
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The purpose of this study is to investigate efficacy and safety of intra-operative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection. The hypothesis is intra-operative intervention might be the best timing for cancer cells killing by cytotoxic agents, when most of residual cancer cells may get a rapid growth after tumor debulking and may become more chemotherapy-sensitive. A three-step procedure is designed for intra-operative chemotherapy with 5-FU of 1500 mg/m2, including step 1 of intraluminal 5-FU injection with 1000 mg/m2 at beginning of resection, step 2 of 200mg/m2 5-FU injection into portal vein system via mesentery vein after tumor removal and finish of bowel reconstruction, and step 3 of 300mg/m2 5-FU left into the abdominal cavity before incision closure. The controlled arm receive curative resection only. All the other treatments will stick to the guidelines.

Official Title
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A Prospective,Single-center,Randomized,Controlled Phase III Clinical Study Comparing Efficacy and Safety of Intraoperative Chemotherapy With 5-Fluorouracil Plus Curative Resection Versus Surgery Alone for Patients With Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Procedure: curative resection for colorectal cancer
* Drug: intra-operative 5-FU chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed as adenocarcinoma of colon and rectum age 18-75 years eligible for curative surgical resection performance score: ECOG 0-1 normal blood cells counts: WBC ≥ 4.0×10*9/L，PLT ≥ 100×10*9/L normal blood chemistry test: ALT/AST ≤ 2.5 ULN, TBil ≤ 1.5 ULN, BUN ≤ 1.5 ULN,Cr ≤ 1.5 ULN normal ECG no history of other malignant tumors no concomitant anti-cancer therapy Exclusion Criteria: clinical bowel obstruction anticipated into another clinical trial within three months uncontrolled infection, serious internal medical diseases Pregnant or lactating women mentally abnormal patients patients known allergic to 5-FU

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ARM A- surgery alone<br>all cases will receive standard surgical procedures of curative resection for colorectal cancer, without intra-operative chemotherapy. | Procedure: curative resection for colorectal cancer<br>* right hemicolectomy for right colon cancer, transverse colectomy for transverse colon cancer, left hemicolectomy for left colon cancer, sigmoid colectomy for sigmoid colon cancer, and anterior resection or abdominal-perineal resection for rectal cancer.<br>* Other names: curative resection for colorectal cancer.;|
| Experimental: ARM B surgery plus chemotherapy<br>all cases will receive standard surgical procedures described as arm A. In addition, all cases will receive 5-FU chemotherapy during operation. | Procedure: curative resection for colorectal cancer<br>* right hemicolectomy for right colon cancer, transverse colectomy for transverse colon cancer, left hemicolectomy for left colon cancer, sigmoid colectomy for sigmoid colon cancer, and anterior resection or abdominal-perineal resection for rectal cancer.<br>* Other names: curative resection for colorectal cancer.;Drug: intra-operative 5-FU chemotherapy<br>* 5-FU, 1000 mg/m2, injection into bowel lumen at the beginning of resection 5-FU, 200 mg/m2, injection into portal vein via mesentery vein at the end of tumor removal and bowel reconstruction. 5-FU, 300 mg/m2, left in abdominal cavity before incision closure. surgical procedures will be the same as described in ARM A.<br>* Other names: intra-operative 5-FU chemotherapy for colorectal cancer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival | 3 years survival of recurrence-free, metastasisi-free, death-free after randomization. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival | 5 years survival of recurrence-free, metastasis-free, and death-free survival after randomization. | 5 years | 
| safety profiles | complete blood cells counts, blood chemistry testing, all 28-day mortality after operation, all surgery-related complications | 28 days after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal cancer, curative resection, intra-operative chemotherapy, 5-fluorouracil, chemotherapy