Clinical trial NCT03221608: Clinical Analysis of HIPEC for T4 Colorectal Cancer After Surgery
Official title: Clinical Study of the Impact of Hyperthermic Intraperitoneal Chemotherapy on Peritoneal Recurrence and Prognosis of Patients With Stage T4 Colorectal Cancer After Radical Surgery: A Multicentre Randomised Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Colorectal Neoplasms
Keywords: Colorectal Cancer
HIPEC
Peritoneal Carcinomatosis
Lobaplatin
Lead sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital, Sun Yat-Sen University
name: Zhujiang Hospital
name: First Affiliated Hospital of Jinan University
name: The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
name: Second Affiliated Hospital of Guangzhou Medical University
name: Guangzhou General Hospital of Guangzhou Military Command
name: Tcm-integrated Cancer Center of Southern Medical University
name: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
name: Nanfang Hospital, Southern Medical University
name: Guangdong Provincial Hospital of Traditional Chinese Medicine
First posted: 2017-07-18
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This multicentric study aims to determine if hyperthermic intraperitoneal chemotherapy (HIPEC) will help to prevent the development of peritoneal carcinomatosis in addition to the standard adjuvant systemic treatment after surgery.

Detailed description: Background:

Colorectal cancer (CRC) is the third most common malignancy worldwide, nearly 1.4 million new cases every year, for about 694000 deaths. Surgery is the primary treatment and results in a cure rate of approximately 50% of the patients. However, recurrence following surgery is a major problem, the second most common site of recurrence was peritoneum, which was as a result of the intraperitioneal free cancer cells (FCC) and microscopic cancer (MC). The remaining free cancers and microscopic cancer in abdominal cavity can not be killed completely because of the "peritoneal-plasma barrier" and "non-sufficient drug concentration in abdominal cavity by systemic venous chemotherapy". In recent years, hyperthermic intraperitioneal chemotherapy(HIPEC) has already been shown to be effective in improving the 5 year survival rate of colorectal cancer. However, lots of clinically studies for patients with colorectal cancer are advanced, it is not sure yet whether surgery combined with HIPEC is effective on decreasing the rate of peritoneal carcinomatosis in T4 stage colorectal cancer. The efficacy tend to be magnified when stage T4 patients account for less, confusing HIPEC for treatment of patients with advanced colorectal cancer. Therefore, the aim of this study is to investigate the clinical efficacy of HIPEC in T4 stage patients, ruling out the effects of different T stages on curative effect. The results of this study will hopefully provide the clinical basis for improving the prognosis of patients with advanced colorectal cancer.

Study design： This is a multicenter study in which 300 patients with T4 colorectal cancer will be randomized to surveillance alone (control group) or HIPEC (experimental group) after resection of the primary tumor, either by laparoscopy or open approach. Subsequently, all patients started mfolfox6 chemotherapy after operation in a month. Adverse reaction of chemotherapy during chemotherapy and post chemotherapy period will be recorded.

Study population:

The patients with colorectal cancer (T4N0-2M0) will undergo a curative resection by laparoscopy or open approach.

Intervention:

HIPEC equipment used in the perfusion fluid (Lobaplatin of 50mg completely dissolved in 3000ml saline solution) is headed to 43℃. Then, it is injected into the peritoneal cavity by flow velocity of 200-400ml/min for 60 minutes.

Outcomes:

Primary endpoint is incidence of endoperitoneal recurrence at 36 months. Secondary endpoints are disease-free survival, overall survival, incidence of peritoneal carcinomatosis at end of follow-up with or without concomitant liver/lung metastases, quality of life and morbidity rate.

Eligibility criteria: Inclusion Criteria:

1. Histologically-proven colorectal adenocarcinoma
2. Patients with colon cancer or intraperitoneal rectal cancer with clinical (by CT) T4 tumors, any N, M0
3. Signed informed consent
4. White blood cell count of at least 3000/mm3, platelet count of at least 100.000/mm3
5. No bleeding diathesis or coagulopathy
6. Patients without chemotherapy, radiation or other anti-cancer treatment before the clinical trial

Exclusion Criteria:

1. Liver and/or lung metastases
2. Pregnant women or likely to be pregnant
3. Severe hepatic and / or renal dysfunction
4. Impossibility of an adequate follow-up
5. Without history of cancer during last 5 years
6. Other concurrent chemotherapy
7. Severe or uncontrolled mental illness
8. Patients with epilepsy required to be treated

Primary outcomes:
measure: Incidence of endoperitoneal recurrence at 36 months
timeFrame: 36 months
Secondary outcomes:
measure: Disease-free survival (DFS)
timeFrame: 3 years
measure: Disease-free survival (DFS)
timeFrame: 5 years
measure: Overall survival (OS)
timeFrame: 3 years
measure: Overall survival (OS)
timeFrame: 5 years
measure: Quality of life
timeFrame: 3 years
measure: HIPEC toxicity rate
timeFrame: 1 month
measure: HIPEC toxicity rate
timeFrame: 6 month
Other outcomes:
Locations:
Study officials:
affiliation: Sixth Affiliated Hospital, Sun Yat-sen University
name: MeiJin Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: