Clinical trial NCT02179489: Surgery With HIPEC in Treating Patients With a High Risk of Developing Colorectal Peritoneal Carcinomatosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malignant Neoplasm of Large Intestine TNM Staging Primary Tumor (T) T4
Peritoneal Carcinomatosis
Keywords: Peritoneal carcinomatosis
HIPEC
controlled clinical trial
colorectal cancer
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2014-07-01
Enrollment: 271
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease-free survival
timeFrame: Three years from the date of randomization
Secondary outcomes:
measure: 3 year overall survival
timeFrame: 3 years
measure: Peritoneal disease-free survival
timeFrame: 3 years
measure: 5 year overall survival
timeFrame: 5 years
measure: morbidity
timeFrame: Baseline before any treatment,3 months post operation, 1 year post operation
measure: QOL
timeFrame: Baseline before any treatment,3 months post operation, 1 year post operation
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Union Hospital Fujian Medical University
state: Fujian
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Hangzhou
country: China
facility: The First Affiliated Hospital of College of Medicine Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Second Affiliated Hospitalof Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Jinhua
country: China
facility: Jinhua People's Hospital
state: Zhejiang
city: Shaoxing
country: China
facility: People's Hospital of Shaoxing
state: Zhejiang
city: Yuyao
country: China
facility: Yuyao People's Hospital
state: Zhejiang
Study officials:
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Kefeng Ding, Prof.
role: PRINCIPAL_INVESTIGATOR
References: