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

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ClinicalTrials.gov Identifier: NCT04370925

Recruitment Status : Recruiting

First Posted : May 1, 2020

Last Update Posted : June 16, 2020

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Sponsor:

Collaborators:

Nanfang Hospital, Southern Medical University

Sun Yat-sen University

Sixth Affiliated Hospital, Sun Yat-sen University

First Affiliated Hospital, Sun Yat-Sen University

Guangdong Provincial Hospital of Traditional Chinese Medicine

Guangdong Provincial People's Hospital

Meizhou People's Hospital

First People's Hospital of Foshan

Shantou Central Hospital

Jiangmen Central Hospital

Shenzhen Second People's Hospital

Zhongshan People's Hospital, Guangdong, China

ZhuHai Hospital

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing Hospital

Peking University Cancer Hospital & Institute

Peking University People's Hospital

Fudan University

The Second Affiliated Hospital of Chongqing Medical University

Chongqing University Cancer Hospital

First Affiliated Hospital of Chongqing Medical University

Second Affiliated Hospital, School of Medicine, Zhejiang University

Wuhan Union Hospital, China

Renmin Hospital of Wuhan University

Wuhan University

Sichuan Provincial People's Hospital

West China Hospital

The People's Hospital of Leshan

People's Hospital of Deyang City

Hebei Medical University Fourth Hospital

The First Affiliated Hospital of Nanchang University

The Affiliated Hospital Of Southwest Medical University

The Affiliated Hospital of Xuzhou Medical University

People's Hospital of Guangxi

The Third People's Hospital of Chengdu

The Affiliated Tumor Hospital of Guangxi Medical University

Information provided by (Responsible Party):

Affiliated Cancer Hospital & Institute of Guangzhou Medical University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer	Procedure: Radical colectomy Procedure: HIPEC Drug: Systemic chemotherapy	Phase 3

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	688 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Actual Study Start Date :	June 4, 2020
Estimated Primary Completion Date :	April 30, 2024
Estimated Study Completion Date :	April 30, 2026

Arms and Interventions

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) Procedure: 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 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.

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)

Procedure: 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 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.

Outcome Measures

Primary Outcome Measures :

Peritoneal recurrence free survival [ Time Frame: 3-year ]
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.

Secondary Outcome Measures :

Disease free survival [ Time Frame: 3-year ]
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.
Overall survival [ Time Frame: 5-year ]
Overall survival is calculated from randomization to death from any cause.
Liver metastatic rate [ Time Frame: 3-year ]
Liver metastatic rate is calculated from randomization to to the date of liver metastasis with or without other organ metastasis.
Number of participants with adverse events [ Time Frame: Up to 1 month after the last chemotherapy cycle ]
Incidence of acute and late toxicity

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

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