Efficacy of HIPEC in the Treatment of Locally Advanced Gastric Cancer After radIcal Gastrectomy With D2 (EHTLAGCRGD2)

October 29, 2017 updated by: Affiliated Cancer Hospital & Institute of Guangzhou Medical University

A Phase III Study of Hyperthermic Intraperitoneal Chemotherapy in the Treatment of Locally Advanced Gastric Cancer After radIcal Gastrectomy With D2

HIPEC-01 is a prospective, open, randomized multicenter phase III clinical study conducted in China. To determine the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of locally advanced gastric cancer, patients are randomized into HIPEC group and control group. In HIPEC group, the patients undergo radical gastrectomy with D2 lymphadenectomy and HIPEC with paclitaxel and postoperative chemotherapy. Patients in the control group just undergo radical gastrectomy with D2 lymphadenectomy followed by postoperative chemotherapy. Patients in both groups receive 6-8 cycles of postoperative systemic chemotherapy (XELOX or SOX regimens) and are followed up for 5 years or until death.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Gastric cancer (GC) is the fourth most common cancer, and the second leading cause of cancer-related death worldwide. Advances in diagnostic and therapeutic approaches have achieved long-term survival for early GC. However, receiving perioperative/postoperative systemic chemotherapy and gastrectomy with D1-D2 lymph node dissection, 5-year survival rates of advanced gastric cancer remain under 30%. 40-60% of recurrences are peritoneal and/or locoregional. hyperthermic intraperitoneal chemotherapy (HIPEC) technique is increasingly used in the curative treatment of primary and digestive peritoneal carcinomatosis, in association with cytoreductive surgery. Theoretically, HIPEC eliminates free cancer cells that can be released into peritoneal cavity during the gastrectomy and prevents peritoneal carcinomatosis recurrences. The benefit of using HIPEC as an adjuvant treatment for advanced gastric cancer has been reported in several randomized studies and a meta-analysis. Surgical resection combined with HIPEC significantly reduces the peritoneal recurrences and improves the overall survival of GC patients. But there is not a prospective and randomized phase III clinical study of HIPEC in the treatment of locally advanced gastric cancer after radical surgery in China so far.

In order to evaluate the survival benefit and safety of radical surgery and HIPEC followed by postoperative chemotherapy in local advanced gastric cancer, patients who fulfill the inclusion and exclusion criteria will be recruited in this study and randomized to two treatment groups (HIPEC group and control group). In HIPEC group, the patients undergo radical gastrectomy with D2 lymphadenectomy and HIPEC with paclitaxel and postoperative chemotherapy. Patients in the control group just undergo radical gastrectomy with D2 lymphadenectomy followed by postoperative chemotherapy. Patients in both groups receive 6-8 cycles of postoperative systemic chemotherapy (XELOX or SOX regimens) . Patients are followed up for 5 years and the survival outcome will be analyzed.

Study Type

Interventional

Enrollment (Anticipated)

584

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Xian-Zi Yang, M.M
  • Phone Number: 0086-188-9853-4167
  • Email: 7097359@qq.com

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100853
        • Recruiting
        • Chinese PLA General Hospital
        • Contact:
        • Principal Investigator:
          • Zheng Peng, M.D
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • Recruiting
        • Guangdong General Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yong Li, M.D
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-sen University Cancer Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Zhi-Wei Zhou, M.D
      • Guangzhou, Guangdong, China, 510515
        • Recruiting
        • NanFang Hospital of Southern Medical University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Guo-Xin Li, M.D
      • Guangzhou, Guangdong, China, 510120
        • Recruiting
        • Guangdong Provincial Hospital of Traditional Chinese Medicine
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jin Wang, M.D
      • Guangzhou, Guangdong, China, 510095
        • Recruiting
        • Affiliated Tumor Hospital of Guangzhou Medical University
        • Contact:
    • Hebei
      • Shijiazhuang, Hebei, China, 050000
        • Recruiting
        • The second hospital of Hebei Medical University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Bao-Jun Zhou, M.M
      • Shijiazhuang, Hebei, China, 050011
        • Recruiting
        • Hebei Medical University Fourth Hospital
        • Principal Investigator:
          • Yong Li, M.D
        • Contact:
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150081
        • Recruiting
        • Harbin Medical University Cancer Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Kuan Wang, M.D
    • Henan
      • Zhengzhou, Henan, China, 450008
        • Recruiting
        • Henan Cancer Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Guang-Sen Han
    • Hubei
      • Wuhan, Hubei, China, 430030
        • Recruiting
        • Wuhan Union Hospital, China
        • Contact:
        • Contact:
        • Principal Investigator:
          • Kai-Xiong Tao, M.D
    • Hunan
      • Changsha, Hunan, China, 410011
        • Recruiting
        • The Second Xiangya Hospital of Central South University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Hong-Liang Yao, M.D
    • Tianjin
      • Tianjin, Tianjin, China, 300060
        • Recruiting
        • Tianjin Medical University Cancer Institute and Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Han Liang, M.M
    • Zhejiang
      • Hanzhou, Zhejiang, China, 310022
        • Recruiting
        • Zhejiang Cancer Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Xin-Bao Wang, M.D

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18 < age ≤ 70 years old
  • Male or Non pregnant female
  • The Eastern Cooperative Oncology Group (ECOG) status 0-1
  • T3 or T4 gastric adenocarcinoma (visual determination according to AJCC 2010 7th edition)
  • No distance metastasis, eligible for D2 lymphadenectomy
  • Have not received cytotoxic chemotherapy, radiotherapy or immunotherapy
  • White blood cells > 4,000/mm3
  • neutrophils ≥ 1,500/mm3
  • platelets ≥ 100,000/mm3
  • hemoglobin>9g/l
  • Alanine transaminase (ALT) and aspartate aminotransferase (AST) < or = 2.5 times upper limit of nominal (ULN)
  • total bilirubin (TBIL) < 1.5 times ULN
  • serum creatinine < 1 times ULN
  • Having given written informed consent prior to any procedure related to the study

Exclusion Criteria:

  • Have other cancer within 5 years
  • Existence of distance metastasis during surgey (M1)
  • Prior malignant tumors with detectable signs of recurrence or distant metastasis
  • Poorly controlled disease e.g. atrial fibrillation, stenocardia, cardiac insufficiency, persistent hypertension despite medicinal treatment, ejection fraction<50%
  • Epileptic seizures patients need medicine control
  • Uncontroled mental disease or mental disorder
  • Drug abuse or psychological or social factors affect the judgment of results
  • Contraindication to any therapy contained in this regimen specific to the study
  • Receiving other chemotherapy, radiotherapy or immunotherapy
  • Without given written informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: HIPEC group

Postoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is performed after radical surgery, followed by 6-8 cycles of systemic chemotherapy. The first HIPEC is conducted within 48 h after surgery: Paclitaxel 75 mg/m^2, 43°C, 60min. The second HIPEC is performed after 24 hours of the first HIPEC. The regimens are Paclitaxel 100 mg/m^2, 43°C, 60min.

Systemic chemotherapy (XELOX or SOX regimens):

XELOX regimen: Oxaliplatin: 130 mg/m^2, IV, d1; Capecitabine: 1 g/m^2 bid, days 1-14, every 3 weeks for a total of 6-8 cycles.

If XELOX regimen is not conducted in some collaborators, SOX regimen is also permitted. The regimen is Oxaliplatin: 130 mg/m^2, IV, d1; S-1, 40-60 mg/m^2 bid, po, day 1-14, every 3 weeks for a total of 6-8 cycles.
Procedure: D2 lymphadenectomy
Other Names:
  • surgical resection or radical surgery
Procedure: Hyperthermic Intraperitoneal Chemotherapy
The first HIPEC is conducted within 48 h after surgery: Normal saline 3000 -4000ml, Paclitaxel 75mg/m^2, 43°C, 60min. The second HIPEC is performed after 24 hours of the first HIPEC. The regimens are Paclitaxel 100 mg/m^2, 43°C, 60min.
Other Names:
  • HIPEC
Drug: Systemic chemotherapy (XELOX or SOX regimens)

XELOX regimen: Oxaliplatin: 130 mg/m^2, IV, d1; Capecitabine: 1 g/m^2 bid, days 1-14, every 3 weeks for a total of 6-8 cycles.

SOX regimen: Oxaliplatin: 130 mg/m^2, IV, d1; S-1, 40 mg/m^2 bid, po, day 1-14 (S-1: BSA <1.25m^2, 40mg bid, 1.25m^2≤ BSA ≤1.5m^2, 50mg bid, BSA>1.5m^2, 60 mg bid) bid, d1-14, po, every 3 weeks for a total of 6-8 cycles.

Other Names:
  • XELOX or SOX regimens
PLACEBO_COMPARATOR: Control group

6-8 cycles of systemic chemotherapy (XELOX or SOX regimens) were performed after radical gastrectomy with D2 lymphadenectomy.

XELOX regimen is Oxaliplatin: 130 mg/m^2, IV, d1; Capecitabine: 1 g/m^2 bid, days 1-14, every 3 weeks for a total of 6-8 cycles.

If XELOX regimen is not conducted in some collaborators, SOX regimen as comment systemic chemotherapy in Asia is also permitted to treat the patients. The treatment bundles are listed as follows: Oxaliplatin: 130 mg/m^2, IV, d1; S-1, 40-60 mg/m^2 bid (S-1: BSA <1.25m^2, 40mg bid, 1.25m^2≤ BSA ≤1.5m^2, 50mg bid, BSA>1.5m^2, 60 mg bid), po, day 1-14, every 3 weeks for a total of 6-8 cycles.
Procedure: D2 lymphadenectomy
Other Names:
  • surgical resection or radical surgery
Drug: Systemic chemotherapy (XELOX or SOX regimens)

XELOX regimen: Oxaliplatin: 130 mg/m^2, IV, d1; Capecitabine: 1 g/m^2 bid, days 1-14, every 3 weeks for a total of 6-8 cycles.

SOX regimen: Oxaliplatin: 130 mg/m^2, IV, d1; S-1, 40 mg/m^2 bid, po, day 1-14 (S-1: BSA <1.25m^2, 40mg bid, 1.25m^2≤ BSA ≤1.5m^2, 50mg bid, BSA>1.5m^2, 60 mg bid) bid, d1-14, po, every 3 weeks for a total of 6-8 cycles.

Other Names:
  • XELOX or SOX regimens

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
5-year overall survival
Time Frame: 5 years
assess overall survival during 5 years in both study arms
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
5-year progression-free survival
Time Frame: 5 years
assess progression-free survival rate during 5 years in both study arms
5 years
liver metastatic rate
Time Frame: 5 years
calculate the percent of liver metastatic in both two arms during 5 years
5 years
local recurrence rate
Time Frame: 5 years
calculate the percent of local recurrence in both two arms during 5 years
5 years
side effects
Time Frame: 5 years
determine percent of adverse events or side effects according to NCI criteria, Common Terminology Criteria for AE (CTCAE 4.0).
5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
CEA mRNA expression of peritoneal lavage fluid
Time Frame: Through study completion, an average of 3 year
Quantitative RT-PCR is used to analyze CEA mRNA expression of peritoneal lavage fluid before and after D2 lymphadenectomy between two arms
Through study completion, an average of 3 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Affiliated Cancer Hospital & Institute of Guangzhou Medical University

Collaborators

Zhejiang Cancer Hospital
Guangdong Provincial Hospital of Traditional Chinese Medicine
Sun Yat-sen University
Chinese PLA General Hospital
The Second Hospital of Hebei Medical University
Henan Cancer Hospital
Nanfang Hospital of Southern Medical University
Tianjin Medical University Cancer Institute and Hospital
Guangdong Provincial People's Hospital
Wuhan Union Hospital, China
Hebei Medical University Fourth Hospital
Central South University
Harbin Medical University

Investigators

  • Study Director: shuzhong cui, M.D, Affiliated Tumor Hospital of Guangzhou Medical University Recruiting

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 11, 2015

Primary Completion (ANTICIPATED)

January 1, 2022

Study Completion (ANTICIPATED)

January 1, 2022

Study Registration Dates

First Submitted

January 29, 2015

First Submitted That Met QC Criteria

February 4, 2015

First Posted (ESTIMATE)

February 5, 2015

Study Record Updates

Last Update Posted (ACTUAL)

October 31, 2017

Last Update Submitted That Met QC Criteria

October 29, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HIPEC-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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