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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04370925
• Other study ID #: HIPEC-06
• Status: Recruiting
• Phase: Phase 3
• Start date: June 4, 2020
• Est. completion date: April 30, 2026

Study information

• Verified date: April 2020
• Source: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• Contact: Shuzhong Cui, MD
• Phone: 086-13802513800
• Email: cuishuzhong[@]gzhmu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 688
• Est. completion date: April 30, 2026
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Colorectal Cancer
• Colorectal Neoplasms
• Peritoneal Neoplasms

Intervention

Procedure:
• Radical colectomy
Patients undergo radical resection of the primary colorectal cancer(open or laparoscopic/robotic)
• HIPEC
HIPEC(simultaneously or within 2days after resection) with mitomycin c (30 mg/m2) at 43°C for 90 minutes.

Drug:
• Systemic chemotherapy
Systemic chemotherapy regimens: CapeOx and mFOLFOX6 are preferred for stage ? 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 stage?patiens, regimens recommend by NCCN guide line(2019 v1) are acceptable.

Locations

Country	Name	City	State
China	Beijing Hospital	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Peking University Cancer Hospital & Institute	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	West China Hospital,Sichuan University	Chendu	Sichuan
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	The Third Peoples' Hospital of Chengdu	Chengdu	Sichuan
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	People'S Hospital of Deyang City	Deyang	Sichuan
China	The First People's Hospital of FoShan (Affiliated FoShan Hospital of Sun Yat-sen University)	Foshan	Guangdong
China	Affiliated Cancer Hospital & Institute of Guangzhou Medical University	Guangzhou	Guangdong
China	Guangdong Provincal people's Hospital	Guangzhou	Guangdong
China	Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The Six Affiliated Hospital,Sun Yat-sen University	Guangzhou	Guangdong
China	The Second Affiliated Hospital,Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	JiangMen Central Hospital Affiliated JiangMen Hospital Of SUN YAT-SEN University	Jiangmen	Guangdong
China	Leshan people's Hospital	Leshan	Sichuan
China	The Affiliated hospital of southwest medical university	Luzhou	Sichuan
China	MeiZhou People's Hospital	Meizhou	Guangdong
China	the First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	People's hospital of guangxi zhuang autonomous region	Nanning	Guangxi Zhuang Autonomous Region
China	The Affiliated Tumor Hospital of Guangxi Medical University	Nanning	Guangxi Zhuang Autonomous Region
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Affiliated Shantou Hospital of Sun Yat-sen University	Shantou	Guangdong
China	Shenzhen Second People's Hospital	Shenzhen	Guangdong
China	Hebei Medical University Fourth Hospital	Shijiazhuang	Hebei
China	Union Hospital,Tongji Medical College, Huazhong Uninersity of Science and Technolgy	Wuhan	Hubei
China	Wuhan University Renmin Hospital	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	Zhongshan City People's Hospital	Zhongshan	Guangdong
China	Zhuhai People's Hospital, Zhuhai hospital affiliated with Jinan University	Zhuhai	Guangdong

Sponsors (37)

Lead Sponsor

Collaborator

Affiliated Cancer Hospital & Institute of Guangzhou Medical University

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Overall survival	Overall survival is calculated from randomization to death from any cause.	5-year
Secondary	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
Secondary	Number of participants with adverse events	Incidence of acute and late toxicity	Up to 1 month after the last chemotherapy cycle