Efficacy of HIPEC in Patients With Colorectal Cancer at High Risk of Peritoneal Carcinomatosis

A Multicenter Prospective Randomized Controlled Clinical Trial of Hyperthermic Intraperitoneal Chemotherapy After Colectomy in Patients With Colorectal Cancer at High Risk of Peritoneal Carcinomatosis

The purpose of this study is to determine the efficacy of adjuvant HIPEC with Mitomycin C after colectomy in the treatment of colorectal cancer patients at high risk of peritoneal carcinomatosis.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Procedure: Radical colectomy; Drug: Systemic chemotherapy; Procedure: HIPEC

Detailed Description

The effectiveness of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) have been addressed for the treatment of peritoneal carcinomatosis in selected patients. However, prophylactic HIPEC in colorectal cancer patients at high risk of metachronous peritoneal metastases remained controversial. In this study, patients with colorectal cancer cT4N0-2M0(AJCC/UICC staging system 8th edition) and planed to undergo intentionally colectomy (laparotomy, laparoscopy，or robotic ) are randomized into HIPEC group and control group. In HIPEC group, closed HIPEC is performed with Mitomycin C(30mg/m2) at 43 °C for 90 minutes, simultaneously or within 2 days after colectomy and followed by systemic chemotherapy. For the patients in the control group, systemic chemotherapy were administered after colectomy. The primary endpoint is peritoneal recurrence-free survival (pRFS) rate. Secondary end points include overall survival (OS) rate, disease free survival (DFS) rate, liver metastatic rate, toxic effects, quality of life scores. All efficacy analyses are conducted in the intention-to-treat population, per-protocol population and pT4 subgroups due to pathologic tumor invasion can not be acquired before HIPEC. Safety analysis include only patients who receive their randomly assigned treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 688
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Shuzhong Cui, MD; Phone Number: 086-13802513800; Email: cuishuzhong@gzhmu.edu
• Study Contact Backup: Name: Tianpei Guan, MD; Phone Number: 086-13660895051; Email: dr_guan@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Not yet recruiting
      • Peking University People's Hospital
      • Contact: Bin Liang, MD; Phone Number: 0086-136-8144-4694; Email: 13681444694@163.com
      • Principal Investigator: Bin Liang, MD
      • Sub-Investigator: Chao Wang, MD
    • Beijing, Beijing, China
      • Not yet recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Xishan Wang, MD; Phone Number: 086-13552367779; Email: Wxshan1208@126.com
      • Principal Investigator: Xishan Wang, MD
      • Sub-Investigator: Wei Pei, MD
    • Beijing, Beijing, China
      • Not yet recruiting
      • Beijing Hospital
      • Contact: Gang Zhao, MM; Phone Number: 13910714396; Email: njg656@163.com
      • Principal Investigator: Gang Zhao, MM
      • Sub-Investigator: Hua Yang, MM
    • Beijing, Beijing, China
      • Not yet recruiting
      • Peking University Cancer Hospital & Institute
      • Contact: Aiwen Wu, MD; Phone Number: 086-13911577190; Email: wuaw@sina.com
      • Sub-Investigator: Qiushi Dong, MM
  • Chongqing
    • Chongqing, Chongqing, China
      • Not yet recruiting
      • Chongqing Cancer Hospital
      • Contact: Hao Sun, MD; Phone Number: 086-13508370438; Email: sunhao68@sina.com
      • Principal Investigator: Hao Sun, MD
      • Sub-Investigator: Miao He, MD
    • Chongqing, Chongqing, China
      • Not yet recruiting
      • First Affiliated Hospital of Chongqing Medical University
      • Contact: Zhengqiang Wei, MD; Phone Number: 086-13228675636; Email: 384535713@qq.com
      • Sub-Investigator: Zhengqiang Wei, MD
    • Chongqing, Chongqing, China
      • Not yet recruiting
      • Second Affiliated Hospital of Chongqing Medical University
      • Contact: Jijian Wang, MD; Phone Number: 086-13908304080; Email: Wangjj1963@163.com
      • Principal Investigator: Jijian Wang, MD
  • Guangdong
    • Foshan, Guangdong, China
      • Not yet recruiting
      • The First People's Hospital of FoShan (Affiliated FoShan Hospital of Sun Yat-sen University)
      • Contact: Longqing Cheng, MM; Phone Number: 18038863563; Email: 13702939022@139.com
      • Principal Investigator: Longqing Cheng, MM
      • Sub-Investigator: Yan-an Gao, MM
    • Guangzhou, Guangdong, China, 510060
      • Not yet recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Zhizhong Pan, MD; Phone Number: 086-13719388166; Email: panzz@sysucc.org.cn
      • Principal Investigator: Zhizhong Pan, MD
      • Sub-Investigator: Fulong Wang, MD
    • Guangzhou, Guangdong, China, 510515
      • Not yet recruiting
      • Nanfang Hospital of Southern Medical University
      • Contact: Haijun Deng, MD; Phone Number: 0086-13189096629; Email: navyd999@163.com
      • Principal Investigator: Haijun Deng, MD
      • Sub-Investigator: Kai Sun, MD
    • Guangzhou, Guangdong, China
      • Not yet recruiting
      • The First Affiliated Hospital, Sun Yat-sen University
      • Contact: Chuangqi Chen, MD; Phone Number: 086-13719334878; Email: 2632864588@qq.com
      • Principal Investigator: Chuangqi Chen, MD
      • Sub-Investigator: Jianhui Chen, MD
    • Guangzhou, Guangdong, China, 510080
      • Not yet recruiting
      • Guangdong Provincal People's Hospital
      • Contact: Yong Li, MD; Phone Number: 0086-138-2217-7479; Email: liyong@gdph.org.cn
      • Contact: M.M
      • Sub-Investigator: ZeJian Lv, MM
    • Guangzhou, Guangdong, China, 510095
      • Recruiting
      • Affiliated Cancer Hospital & Institute of Guangzhou Medical University
      • Contact: Shuzhong Cui, MD; Phone Number: 0086-138-0251-3800; Email: cuishuzhong@126.com
      • Contact: Tianpei Guan, MD; Phone Number: 0086-136-6089-5051; Email: dr_guan@126.com
      • Principal Investigator: Shuzhong Cui, MD
      • Sub-Investigator: Tianpei Guan, MD
    • Guangzhou, Guangdong, China, 510120
      • Not yet recruiting
      • Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
      • Principal Investigator: Wei Wang, MD
      • Contact: Wei Wang, MD; Phone Number: 0086-13922255515; Email: ww1640@yeah.net
      • Sub-Investigator: WenJun Xiong, MD
    • Guangzhou, Guangdong, China
      • Not yet recruiting
      • The Six Affiliated Hospital,Sun Yat-sen University
      • Contact: Meijin Huang, MD; Phone Number: 086-13924073322; Email: 13924073322@139.com
      • Sub-Investigator: Wei Chen, MD
    • Jiangmen, Guangdong, China
      • Not yet recruiting
      • JiangMen Central Hospital Affiliated JiangMen Hospital Of SUN YAT-SEN University
      • Contact: Chao Li, BD; Phone Number: 13902888981; Email: Lichao8981@163.com
      • Principal Investigator: Chao Li, BD
      • Sub-Investigator: Wenchuan Jiang, MM
    • Meizhou, Guangdong, China
      • Recruiting
      • Meizhou People's Hospital
      • Contact: Zuguang Zuguang, MM; Phone Number: 086-13502523063; Email: wuzg1913@163.com
      • Principal Investigator: Zuguang Zuguang, MM
      • Sub-Investigator: Haijing Zeng, MM
    • Shantou, Guangdong, China
      • Not yet recruiting
      • Affiliated Shantou Hospital of Sun Yat-sen University
      • Contact: Xiaozhong Wang, MM; Phone Number: 086-13809658922; Email: 103776710@qq.com
      • Principal Investigator: Xiaozhong Wang, MM
      • Sub-Investigator: Chufa Zheng, MM
    • Shenzhen, Guangdong, China
      • Not yet recruiting
      • Shenzhen Second People's Hospital
      • Contact: Haitao Zhang, MM; Phone Number: 13903025325; Email: www.13903025325.@163.com
      • Principal Investigator: Haitao Zhang, MM
      • Sub-Investigator: Yuanzhi Tang, MM
    • Zhongshan, Guangdong, China
      • Not yet recruiting
      • Zhongshan City People's Hospital
      • Contact: Yao Wang, MD; Phone Number: 18826006277; Email: tongjimc@126.com
      • Principal Investigator: Yao Wang, MD
      • Sub-Investigator: Kai Li, MM
    • Zhuhai, Guangdong, China
      • Not yet recruiting
      • Zhuhai People's Hospital, Zhuhai hospital affiliated with Jinan University
      • Contact: Hui Liang, BD; Phone Number: 086-13702760386; Email: zhlianghui@126.com
      • Principal Investigator: Hui Liang, BD
      • Sub-Investigator: Yaoming Huang, MM
  • Guangxi Zhuang Autonomous Region
    • Nanning, Guangxi Zhuang Autonomous Region, China
      • Not yet recruiting
      • People's Hospital of Guangxi Zhuang Autonomous Region
      • Contact: Wei Mai, BS; Email: 13977154858@139.com
      • Principal Investigator: Wei Mai, BS
      • Sub-Investigator: Lei Li, MD
      • Sub-Investigator: Xiaotong Wang, MD
    • Nanning, Guangxi Zhuang Autonomous Region, China
      • Not yet recruiting
      • The Affiliated Tumor Hospital of Guangxi Medical University
      • Principal Investigator: Jiansi Chen
      • Contact: Jiansi Chen
  • Hebei
    • Shijiazhuang, Hebei, China
      • Not yet recruiting
      • Hebei Medical University Fourth Hospital
      • Contact: Bin Yu, MM; Phone Number: 13832329699; Email: yubinli_68@163.com
      • Principal Investigator: Bin Yu, MM
      • Sub-Investigator: Zhenya Zhang, MD
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Union Hospital,Tongji Medical College, Huazhong Uninersity of Science and Technolgy
      • Contact: Kaixiong Tao, MD; Phone Number: 0086-135-0715-5452; Email: tao_kaixiong@163.com
      • Principal Investigator: Kaixiong Tao, MD
      • Sub-Investigator: Chuanqing Wu, MD
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Wuhan University Renmin Hospital
      • Contact: Yongbin Zheng, MD; Phone Number: 086-13871189698; Email: 13871189698@163.com
      • Principal Investigator: Yongbin Zheng, MD
      • Sub-Investigator: Chao Yang, MD
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Zhongnan Hospital of Wuhan University
      • Contact: Congqing Jiang, MD; Phone Number: 086-18971525805; Email: wb002554@whu.edu.cn
      • Principal Investigator: Congqing Jiang, MD
      • Principal Investigator: Qun Qian, MD
  • Jiangsu
    • Xuzhou, Jiangsu, China
      • Not yet recruiting
      • The Affiliated Hospital of Xuzhou Medical University
      • Contact: Jun Song, MD; Phone Number: 15105200058
      • Principal Investigator: Jun Song, MD
      • Sub-Investigator: Haixiao Fu, MM
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Not yet recruiting
      • The First Affiliated Hospital of Nanchang University
      • Contact: Zhigang Jie, MD; Phone Number: 086-13707918042; Email: jiezg123@126.com
      • Principal Investigator: Zhigang Jie, MD
      • Sub-Investigator: Tao Xiao, MD
  • Shanghai
    • Shanghai, Shanghai, China
      • Not yet recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Guoxiang Cai, MD; Phone Number: 086-18017312703; Email: gxcai@fudan.edu.cn
  • Sichuan
    • Chendu, Sichuan, China
      • Not yet recruiting
      • West China Hospital,Sichuan University
      • Principal Investigator: Ziqiang Wang, MD
      • Contact: Ziqiang Wang, MD; Phone Number: 086-18980602028; Email: wangzqzyh@163.com
      • Sub-Investigator: Xiangbing Deng, MD
    • Chengdu, Sichuan, China, 610072
      • Recruiting
      • Sichuan Provincial People's Hospital
      • Contact: Minghui Pang, MD; Phone Number: 0086-134-0282-1952; Email: pangmh2000@163.com
      • Principal Investigator: Minghui Pang, MD
    • Chengdu, Sichuan, China
      • Not yet recruiting
      • The Third Peoples' Hospital of Chengdu
      • Contact: Yanjun Liu, MD; Email: 365184541@qq.com
      • Principal Investigator: Yanjun Liu, MD
      • Sub-Investigator: Yuanchuan Zhang, MD
    • Deyang, Sichuan, China
      • Not yet recruiting
      • People's Hospital of Deyang City
      • Contact: Gang Mai, MD; Phone Number: 086-15283831000; Email: 1026823581@qq.com
      • Principal Investigator: Gang Mai, MD
      • Sub-Investigator: Zhen Liu, MD
    • Leshan, Sichuan, China
      • Not yet recruiting
      • Leshan People's Hospital
      • Contact: Jian Wang, BD; Phone Number: 086-13808138498; Email: Wjls1963@sina.com
      • Principal Investigator: Jian Wang, BD
    • Luzhou, Sichuan, China
      • Not yet recruiting
      • The Affiliated Hospital of Southwest Medical University
      • Contact: Liang Xu, MM; Phone Number: 086-13708289307; Email: XUL1104@163.com
      • Principal Investigator: Liang Xu, MM
      • Sub-Investigator: Hui Yao, MD
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • The Second Affiliated Hospital,Zhejiang University School of Medicine
      • Contact: Kefeng Ding, MD; Phone Number: 086-13906504783; Email: dingkefeng@zju.edu.cn
      • Principal Investigator: Kefeng Ding, MD
      • Sub-Investigator: Lifeng Sun, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 18 and 70 years
• Nonpregnant or breast-feeding women
• ECOG status 0-1
• Colorectal adenocarcinoma or mucinous adenocarcinoma;
• Intraoperative confirmed cT4N0-2M0 Colorectal cancer (visual determination - according to AJCC 8th edition) without previous anti-cancer treatment and R0 resection could be achieved
• Laboratory tests within 2 weeks before Randomization：Neutrophil ≥ 2.0 /mm3, , platelets ≥ 100,000/mm3, hemoglobin≥90g/l, Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ×ULN), total bilirubin(TBIL)≤ 1.5 × ULN, serum creatinine ≤ 1.5 ×ULN
• Written informed consent

Exclusion Criteria:

• Rectal cancer below peritoneal reflection
• Concurrent with or have other cancer within the past 5 years ( except for skin basal cell carcinoma, or cervical carcinoma in situ, who have received radical treatment)
• Severe abdominal infection or extensive fibrosis of peritoneal cavity that lead to impossible separation
• Surgical procedures conversion(from robotic or laparoscopic surgery to laparotomy) or emergency surgery due to perforation or obstruction
• Existence of distance metastasis during surgery (M1) or can not achieve R0 resection
• Contraindiction of mitomycin c(chickenpox or shingles)
• Poorly controlled respiratory or cardiac disease, severe hepatic or renal dysfunction,drug abuse or uncontrolled mental disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Matched control; Patients undergo radical resection of primary colorectal cancer and receive standard adjuvant systemic chemotherapy	Procedure: Radical colectomy; Patients undergo radical resection of the primary colorectal cancer(open or laparoscopic/robotic); Drug: Systemic chemotherapy; Systemic chemotherapy regimens: CapeOx and mFOLFOX6 are preferred for stage Ⅲ patients. CapeOx:oxaliplatin 130 mg/m2 IV d1 + capecitabine 1000mg/m2 po bid d1-14. Repeat every three weeks for eight cycles. mFOLFOX6:oxaliplatin 85 mg/m2 IV d1 + leucovorin calcium 400 mg/m2 IV d1 + 5-FU 400 mg/m2 IV bolus d1 + 5-FU 2400 mg/m2 continuous IV over 46-48 hours d1-2. Repeat every two weeks for twelve cycles. For stageⅡpatiens, regimens recommend by NCCN guide line(2019 v1) are acceptable.
Experimental: HIPEC; Patients undergo radical resection of colorectal cancer and HIPEC simultaneously or within 2 days after primary tumor resection. Followed by standard adjuvant systemic chemotherapy	Procedure: Radical colectomy; Patients undergo radical resection of the primary colorectal cancer(open or laparoscopic/robotic); Drug: Systemic chemotherapy; Systemic chemotherapy regimens: CapeOx and mFOLFOX6 are preferred for stage Ⅲ patients. CapeOx:oxaliplatin 130 mg/m2 IV d1 + capecitabine 1000mg/m2 po bid d1-14. Repeat every three weeks for eight cycles. mFOLFOX6:oxaliplatin 85 mg/m2 IV d1 + leucovorin calcium 400 mg/m2 IV d1 + 5-FU 400 mg/m2 IV bolus d1 + 5-FU 2400 mg/m2 continuous IV over 46-48 hours d1-2. Repeat every two weeks for twelve cycles. For stageⅡpatiens, regimens recommend by NCCN guide line(2019 v1) are acceptable.; Procedure: HIPEC; HIPEC(simultaneously or within 2days after resection) with mitomycin c (30 mg/m2) at 43°C for 90 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peritoneal recurrence free survival	Peritoneal recurrence free survival is calculated from the date of randomization to the date of record peritoneal recurrence(with or without other metastasis), ovarian metastasis, malignant ascites, or death from any cause, whichever occurred first.	3-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival	Disease free survival is calculated from randomization to to the date of a first relapse, the diagnosis of a secondary colorectal cancer after the initial diagnosis, or death from any cause, whichever occurred first.	3-year
Overall survival	Overall survival is calculated from randomization to death from any cause.	5-year
Liver metastatic rate	Liver metastatic rate is calculated from randomization to to the date of liver metastasis with or without other organ metastasis.	3-year
Number of participants with adverse events	Incidence of acute and late toxicity	Up to 1 month after the last chemotherapy cycle

Collaborators and Investigators

• Sponsor: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• Collaborators: The First Affiliated Hospital of Nanchang University; Chongqing University Cancer Hospital; Guangdong Provincial Hospital of Traditional Chinese Medicine; Wuhan University; Peking University People's Hospital; Sun Yat-sen University; Fudan University; Cancer Institute and Hospital, Chinese Academy of Medical Sciences; First Affiliated Hospital, Sun Yat-Sen University; West China Hospital; Peking University Cancer Hospital & Institute; Second Affiliated Hospital, School of Medicine, Zhejiang University; Nanfang Hospital of Southern Medical University; Beijing Hospital; Guangdong Provincial People's Hospital; Sixth Affiliated Hospital, Sun Yat-sen University; Wuhan Union Hospital, China; Hebei Medical University Fourth Hospital; Renmin Hospital of Wuhan University; First People's Hospital of Foshan; The Second Affiliated Hospital of Chongqing Medical University; Shenzhen Second People's Hospital; Shantou Central Hospital; Sichuan Provincial People's Hospital; First Affiliated Hospital of Chongqing Medical University; The Affiliated Hospital of Xuzhou Medical University; Zhongshan People's Hospital, Guangdong, China; People's Hospital of Guangxi; The Affiliated Hospital Of Southwest Medical University; ZhuHai Hospital; Jiangmen Central Hospital; Meizhou People's Hospital; The People's Hospital of Leshan; The Third People's Hospital of Chengdu; People's Hospital of Deyang City; The Affiliated Tumor Hospital of Guangxi Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2020
• Primary Completion (Anticipated): April 30, 2024
• Study Completion (Anticipated): April 30, 2026

Study Registration Dates

• First Submitted: April 8, 2020
• First Submitted That Met QC Criteria: April 30, 2020
• First Posted (Actual): May 1, 2020

Study Record Updates

• Last Update Posted (Actual): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 15, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Colorectal cancer; Hyperthermic intraperitoneal chemotherapy; Colectomy; Peritoneal carcinomatosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Abdominal Neoplasms; Carcinoma; Colorectal Neoplasms; Peritoneal Neoplasms
• Other Study ID Numbers: HIPEC-06

Drug and device information, study documents

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