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

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

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.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: curative resection for colorectal cancer; Drug: intra-operative 5-FU chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 695
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Department of Colorectal Surgery, 14Th Floor, Main Building, Sun Yat-Sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ARM A- surgery alone; all cases will receive standard surgical procedures of curative resection for colorectal cancer, without intra-operative chemotherapy.	Procedure: curative resection for colorectal cancer; 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.; Other Names: curative resection for colorectal cancer.
Experimental: ARM B surgery plus chemotherapy; 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; 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.; Other Names: curative resection for colorectal cancer.; Drug: intra-operative 5-FU chemotherapy; 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.; Other Names: intra-operative 5-FU chemotherapy for colorectal cancer

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: zhizhong pan, MD, PhD, Sun Yat-sen University

Publications and helpful links

General Publications

• Zhang RX, Lin JZ, Lei J, Chen G, Li LR, Lu ZH, Ding PR, Huang JQ, Kong LH, Wang FL, Li C, Jiang W, Ke CF, Zhou WH, Fan WH, Liu Q, Wan DS, Wu XJ, Pan ZZ. Safety of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection: a randomized, multicenter, prospective, phase III IOCCRC trial (IOCCRC). J Cancer Res Clin Oncol. 2017 Dec;143(12):2581-2593. doi: 10.1007/s00432-017-2489-0. Epub 2017 Aug 28.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: November 1, 2011
• First Submitted That Met QC Criteria: November 3, 2011
• First Posted (Estimate): November 4, 2011

Study Record Updates

• Last Update Posted (Estimate): August 11, 2016
• Last Update Submitted That Met QC Criteria: August 10, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: colorectal cancer; chemotherapy; 5-fluorouracil; curative resection; intra-operative chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: SYSU 5010-2010016 IOCCRC