Clinical Analysis of HIPEC for T4 Colorectal Cancer After Surgery

Clinical Study of the Impact of Hyperthermic Intraperitoneal Chemotherapy on Peritoneal Recurrence and Prognosis of Patients With Stage T4 Colorectal Cancer After Radical Surgery: A Multicentre Randomised Clinical Trial

This multicentric study aims to determine if hyperthermic intraperitoneal chemotherapy (HIPEC) will help to prevent the development of peritoneal carcinomatosis in addition to the standard adjuvant systemic treatment after surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Procedure: Surgery without HIPEC; Procedure: Surgery and HIPEC with Lobaplatin

Detailed Description

Background:

Colorectal cancer (CRC) is the third most common malignancy worldwide, nearly 1.4 million new cases every year, for about 694000 deaths. Surgery is the primary treatment and results in a cure rate of approximately 50% of the patients. However, recurrence following surgery is a major problem, the second most common site of recurrence was peritoneum, which was as a result of the intraperitioneal free cancer cells (FCC) and microscopic cancer (MC). The remaining free cancers and microscopic cancer in abdominal cavity can not be killed completely because of the "peritoneal-plasma barrier" and "non-sufficient drug concentration in abdominal cavity by systemic venous chemotherapy". In recent years, hyperthermic intraperitioneal chemotherapy(HIPEC) has already been shown to be effective in improving the 5 year survival rate of colorectal cancer. However, lots of clinically studies for patients with colorectal cancer are advanced, it is not sure yet whether surgery combined with HIPEC is effective on decreasing the rate of peritoneal carcinomatosis in T4 stage colorectal cancer. The efficacy tend to be magnified when stage T4 patients account for less, confusing HIPEC for treatment of patients with advanced colorectal cancer. Therefore, the aim of this study is to investigate the clinical efficacy of HIPEC in T4 stage patients, ruling out the effects of different T stages on curative effect. The results of this study will hopefully provide the clinical basis for improving the prognosis of patients with advanced colorectal cancer.

Study design： This is a multicenter study in which 300 patients with T4 colorectal cancer will be randomized to surveillance alone (control group) or HIPEC (experimental group) after resection of the primary tumor, either by laparoscopy or open approach. Subsequently, all patients started mfolfox6 chemotherapy after operation in a month. Adverse reaction of chemotherapy during chemotherapy and post chemotherapy period will be recorded.

Study population:

The patients with colorectal cancer (T4N0-2M0) will undergo a curative resection by laparoscopy or open approach.

Intervention:

HIPEC equipment used in the perfusion fluid (Lobaplatin of 50mg completely dissolved in 3000ml saline solution) is headed to 43℃. Then, it is injected into the peritoneal cavity by flow velocity of 200-400ml/min for 60 minutes.

Outcomes:

Primary endpoint is incidence of endoperitoneal recurrence at 36 months. Secondary endpoints are disease-free survival, overall survival, incidence of peritoneal carcinomatosis at end of follow-up with or without concomitant liver/lung metastases, quality of life and morbidity rate.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: MeiJin Huang, MD; Phone Number: 86-020-38250745; Email: meijinhuang3@163.com
• Study Contact Backup: Name: Wei Chen, MD; Phone Number: 86-020-38250745; Email: chenw47@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically-proven colorectal adenocarcinoma
2. Patients with colon cancer or intraperitoneal rectal cancer with clinical (by CT) T4 tumors, any N, M0
3. Signed informed consent
4. White blood cell count of at least 3000/mm3, platelet count of at least 100.000/mm3
5. No bleeding diathesis or coagulopathy
6. Patients without chemotherapy, radiation or other anti-cancer treatment before the clinical trial

Exclusion Criteria:

1. Liver and/or lung metastases
2. Pregnant women or likely to be pregnant
3. Severe hepatic and / or renal dysfunction
4. Impossibility of an adequate follow-up
5. Without history of cancer during last 5 years
6. Other concurrent chemotherapy
7. Severe or uncontrolled mental illness
8. Patients with epilepsy required to be treated

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: surgery alone(open/laparoscopic); The patients with colorectal cancer (T4N0-2M0) who have a high risk of developing colorectal Peritoneal Carcinomatosis (PC) undergo curative surgery(open/laparoscopic).	Procedure: Surgery without HIPEC; The patients with colorectal cancer (T4N0-2M0) are undergone a curative resection by laparoscopy or open approach.; Other Names: Standard surgical treatment by laparoscopy or open approach.
Experimental: surgery and HIPEC; Standard surgical treatment and HIPEC with Lobaplatin.	Procedure: Surgery and HIPEC with Lobaplatin; The combination of surgery and HIPEC with Lobaplatin are performed in patients with colorectal cancer (T4N0-2M0).; Other Names: The combination of surgery and HIPEC with Lobaplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of endoperitoneal recurrence at 36 months	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)		3 years
Overall survival (OS)		5 years
Disease-free survival (DFS)		3 years
Disease-free survival (DFS)		5 years
Quality of life	To evaluate quality of life with EORTC QLQ-30 questionnaire	3 years
HIPEC toxicity rate		1 month
HIPEC toxicity rate		6 month

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
• Collaborators: Guangdong Provincial Hospital of Traditional Chinese Medicine; Nanfang Hospital of Southern Medical University; Second Affiliated Hospital, Sun Yat-Sen University; Zhujiang Hospital; First Affiliated Hospital of Jinan University; Affiliated Cancer Hospital & Institute of Guangzhou Medical University; Guangzhou General Hospital of Guangzhou Military Command; Second Affiliated Hospital of Guangzhou Medical University; The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine; Tcm-integrated Cancer Center of Southern Medical University
• Investigators: Principal Investigator: MeiJin Huang, MD, Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2017
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): August 1, 2024

Study Registration Dates

• First Submitted: July 17, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (Actual): July 18, 2017

Study Record Updates

• Last Update Posted (Actual): July 18, 2017
• Last Update Submitted That Met QC Criteria: July 17, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: HIPEC; Colorectal Cancer; Peritoneal Carcinomatosis; Lobaplatin
• 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: zs6yhmjHIPEC2017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No