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

• ClinicalTrials.gov Identifier: NCT04370925
• Recruitment Status: Recruiting
• First Posted: May 1, 2020
• Last Update Posted: June 16, 2020
• Sponsor: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• 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

Tracking Information

• First Submitted Date: April 8, 2020
• First Posted Date: May 1, 2020
• Last Update Posted Date: June 16, 2020
• Actual Study Start Date: June 4, 2020
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 30, 2020)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 30, 2020)

• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of HIPEC in Patients With Colorectal Cancer at High Risk of Peritoneal Carcinomatosis
• 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
• 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.
• 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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer

Intervention

• 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.

Study Arms

• Active Comparator: Matched control
  Patients undergo radical resection of primary colorectal cancer and receive standard adjuvant systemic chemotherapy
  Interventions:

  • Procedure: Radical colectomy
  • Drug: Systemic chemotherapy
• 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
  Interventions:

  • Procedure: Radical colectomy
  • Procedure: HIPEC
  • Drug: Systemic chemotherapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 30, 2020): 688
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2026
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Shuzhong Cui, MD; 086-13802513800; cuishuzhong@gzhmu.edu

Contact: Tianpei Guan, MD; 086-13660895051; dr_guan@126.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04370925
• Other Study ID Numbers: HIPEC-06
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• Original Responsible Party: Same as current
• Current Study Sponsor: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• Original Study Sponsor: Same as current

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

• Investigators: Not Provided
• PRS Account: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• Verification Date: April 2020