Surgery With HIPEC in Treating Patients With a High Risk of Developing Colorectal Peritoneal Carcinomatosis

Randomized Multicentric Phase III Trial Comparing Simple Surgery to Surgery Plus HIPEC (Hyperthermic Intraperitoneal Chemotherapy) With MMC in Colorectal Patients Who Have a High Risk of Developing Colorectal Peritoneal Carcinomatosis

Multicentric randomised trial. The goal of this clinical research study is to learn if hyperthermic intraperitoneal chemotherapy (HIPEC) will help to decrease the rate of peritoneal carcinomatosis(PC) in patients with high risk of developing PC of colorectal cancer. The safety of this treatment will also be studied.

Study Overview

• Status: Completed
• Conditions: Peritoneal Carcinomatosis; Malignant Neoplasm of Large Intestine TNM Staging Primary Tumor (T) T4
• Intervention / Treatment: Procedure: Surgery and Hyperthermic Intraperitoneal Chemotherapy with MMC

Detailed Description

Hyperthermic intraperitoneal chemotherapy(HIPEC) is a recently validated option for the treatment of peritoneal carcinomatosis from colorectal or ovarian origin. This therapeutic program demonstrated a significant improvement of overall survival of the disease. It is not yet known whether surgery followed by HIPEC is effective on decreasing the rate of peritoneal carcinomatosis(PC) in patients with high risk of developing PC of colorectal cancer.Patients with a high risk of developing colorectal Peritoneal Carcinomatosis (PC), defined by Colorectal Cancer With a Resected Minimal Synchronous PC or Ovarian Metastases, or identified T4 by intraoperative pathological diagnosis, or Tumour Rupture in the Abdominal Cavity. If patients with a high risk of developing PC identified by preoperative examination, they will be informed and will sign the consent. After complete resection of their tumor, they will be randomised to surveillance alone (control group) or HIPEC (experimental group). All patients will receive the current standard postoperative adjuvant treatment : 6 months of systemic chemotherapy (currently including FOLFOX4, mFOLFOX6, CapeOx or Capecitabine regimen which could be modified if the standard is modified). Then a work-up is done to find recurrence. If the recurrence occurs, the patient will be treated with the best known treatment.

• Study Type: Interventional
• Enrollment (Actual): 271
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Union Hospital Fujian Medical University
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning cancer hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital Fudan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of College of Medicine Zhejiang University
    • Hangzhou, Zhejiang, China, 310009
      • Second Affiliated Hospitalof Zhejiang University School of Medicine
    • Jinhua, Zhejiang, China, 321000
      • Jinhua People's Hospital
    • Shaoxing, Zhejiang, China, 312000
      • People's Hospital of Shaoxing
    • Yuyao, Zhejiang, China, 315400
      • Yuyao People's hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients presenting with the following history:

  1. Histologically-proven colorectal adenocarcinoma

  2. Presenting at the time of resection of the primary with one of the following 5 criteria (criteria indicating a high risk of developing PC) :

     • Minimal PC, resected at the same time as the primary
     • Rupture of the primary tumour inside the peritoneal cavity,
     • Intraoperative rupture of the primary tumour during surgery
     • Histologically-proven T4 colorectal adenocarcinoma

• Who have received standard systemic adjuvant chemotherapy (6 months of systemic chemotherapy) :

  1. Chemotherapy with FOLFOX4, mFOLFOX6, CapeOx or Capecitabine(the current standard treatment; it can be modified in the future in the two groups, if the standard is modified)
  2. Given on an intent-to-treat basis (it can be stopped prematurely for miscellaneous reasons)
• Patients who do not present any sign of tumour recurrence at the end of these 6 months of chemotherapy

• Patients with the following general characteristics:

  1. Age between 18 and 75 years
  2. Performance Status (ECOG) 0, 1 or 2, life expectancy > 12 weeks
  3. Adequate renal, and bone marrow function: a. Leukocytes >/= 3,000/microL; b. Absolute neutrophil count >/= 1,500/microL; c. Platelets >/= 100,000/Ul; d. Serum creatinine </= 1.5 mg/dL
  4. Hepatic function: a. AST (SGOT)/ALT (SGPT) </= 5 X institutional (Upper Limit of Normal) ULN
  5. Operable patients
  6. Completion of neoadjuvant systemic chemotherapy
• Patients will be informed and a signed consent before initiating any procedure specific to the trial

Exclusion Criteria:

1. Cancers of non colorectal origin
2. Patients presenting with a detectable recurrent tumour
3. History of cancer (excepted cutaneous basal cell carcinoma or in situ carcinoma of the uterine cervix) with a recurrence during the 5 previous years
4. Known HIV, Hepatitis B or Hepatitis C positive
5. Pregnant women or likely to be pregnant
6. Persons under guardianship
7. Subjects deemed unable to comply with study and/or follow-up procedures.
8. Subjects with a known hypersensitivity to protocol systemic chemotherapy that was life-threatening, required hospitalization or prolongation of existing hospitalization, or resulted in persistent or significant disability or incapacity

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; surgery alone
Experimental: Hipec; Surgery and Hyperthermic Intraperitoneal Chemotherapy with MMC	Procedure: Surgery and Hyperthermic Intraperitoneal Chemotherapy with MMC; HIPEC with MMC: Mitomycin C (MMC) (30 mg/m2 of body surface area). Closed technique, as preferred. Duration: 60 minutes. Mean Intra-abdominal Temperature: 43°C.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	DFS	Three years from the date of randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 year overall survival	3-OS	3 years
Peritoneal disease-free survival	PDFS	3 years
5 year overall survival	5-OS	5 years
morbidity	Toxicity induced by HIPEC using the NCI CTC criteria; one month and six months morbidity. Subgroup analysis: pT4; pts. ≤ 40yrs.	Baseline before any treatment,3 months post operation, 1 year post operation
QOL	Duration of operation; return of bowel function; length of hospital stay; return to normal activity; six months and one year QOL, using the SF-36 v1.0; percentage of patients in both arms completing the scheduled postoperative chemotherapy; Subgroup analysis: pT4; pts. ≤ 40yrs.	Baseline before any treatment,3 months post operation, 1 year post operation

Collaborators and Investigators

• Sponsor: Zhejiang University
• Investigators: Principal Investigator: Kefeng Ding, Prof., Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): November 30, 2021
• Study Completion (Actual): November 30, 2021

Study Registration Dates

• First Submitted: June 21, 2014
• First Submitted That Met QC Criteria: June 30, 2014
• First Posted (Estimate): July 1, 2014

Study Record Updates

• Last Update Posted (Actual): June 27, 2022
• Last Update Submitted That Met QC Criteria: June 24, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: colorectal cancer; HIPEC; controlled clinical trial; Peritoneal carcinomatosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; 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; Neoplasms; Carcinoma; Colorectal Neoplasms; Peritoneal Neoplasms
• Other Study ID Numbers: CRCCZ-C01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No