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

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ClinicalTrials.gov Identifier: NCT02356276
Recruitment Status : Recruiting
First Posted : February 5, 2015
Last Update Posted : October 31, 2017
Sponsor:
Collaborators:
Tianjin Medical University Cancer Institute and Hospital
Nanfang Hospital of Southern Medical University
Zhejiang Cancer Hospital
The Second Hospital of Hebei Medical University
Chinese PLA General Hospital
Henan Cancer Hospital
Harbin Medical University
Central South University
Guangdong General Hospital
Wuhan Union Hospital, China
Sun Yat-sen University
Hebei Medical University Fourth Hospital
Guangdong Provincial Hospital of Traditional Chinese Medicine
Information provided by (Responsible Party):
Affiliated Cancer Hospital & Institute of Guangzhou Medical University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Gastric Cancer Procedure: D2 lymphadenectomy Procedure: Hyperthermic Intraperitoneal Chemotherapy Drug: Systemic chemotherapy (XELOX or SOX regimens) Phase 3

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  (Clinical Trial)
Estimated Enrollment : 584 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Study of Hyperthermic Intraperitoneal Chemotherapy in the Treatment of Locally Advanced Gastric Cancer After radIcal Gastrectomy With D2
Actual Study Start Date : May 11, 2015
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: 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 Name: XELOX or SOX regimens




Primary Outcome Measures :
  1. 5-year overall survival [ Time Frame: 5 years ]
    assess overall survival during 5 years in both study arms


Secondary Outcome Measures :
  1. 5-year progression-free survival [ Time Frame: 5 years ]
    assess progression-free survival rate during 5 years in both study arms

  2. liver metastatic rate [ Time Frame: 5 years ]
    calculate the percent of liver metastatic in both two arms during 5 years

  3. local recurrence rate [ Time Frame: 5 years ]
    calculate the percent of local recurrence in both two arms during 5 years

  4. 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).


Other Outcome Measures:
  1. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02356276


Contacts
Contact: shuzhong cui, M.D 0086-138-0251-3800 cuishuzhong@126.com
Contact: Xian-Zi Yang, M.M 0086-188-9853-4167 7097359@qq.com

Locations
China, Beijing
Chinese PLA General Hospital Recruiting
Beijing, Beijing, China, 100853
Contact: Zheng Peng, M.D    0086-137-0132-3669    pengzheng301@sina.com   
Principal Investigator: Zheng Peng, M.D         
China, Guangdong
Sun Yat-sen University Cancer Center Recruiting
Guangzhou, Guangdong, China, 510060
Contact: Zhi-Wei Zhou, M.D    0086-139-0222-2859    zhouzhw@sysucc.org.cn   
Contact: Xiao-Xi Zhu, M.B    0086-138-0881-5489    zhuxx@sysucc.org.cn   
Principal Investigator: Zhi-Wei Zhou, M.D         
Guangdong General Hospital Recruiting
Guangzhou, Guangdong, China, 510080
Contact: Yong Li, M.D    0086-138-2217-7479    yuan821007@126.com   
Contact: Ze-Jian Lv, M.M    0086-137-9819-1490    648593454@qq.com   
Principal Investigator: Yong Li, M.D         
Affiliated Tumor Hospital of Guangzhou Medical University Recruiting
Guangzhou, Guangdong, China, 510095
Contact: shuzhong cui, M.D    0086-138-0251-3800    cuishuzhong@126.com   
Contact: Zhen Tang, M.M    0086-159-2081-9128    57932181@qq.com   
Principal Investigator: shuzhong cui, M.D         
Guangdong Provincial Hospital of Traditional Chinese Medicine Recruiting
Guangzhou, Guangdong, China, 510120
Contact: Jin Wang, M.D    0086-136-0283-8202    gdphtcmwanjin@163.com   
Contact: Wen-Jun Xiong, M.M    0086-159-2055-3177    xiongwj1988@163.com   
Principal Investigator: Jin Wang, M.D         
Nanfang Hospital of Southern Medical University Recruiting
Guangzhou, Guangdong, China, 510515
Contact: Guo-Xin Li, M.D    0086-138-0277-1450    gzliguoxin@163.com   
Contact: Hao Liu, M.D    0086-138-2215-8578    liuhaofbi@163.com   
Principal Investigator: Guo-Xin Li, M.D         
China, Hebei
The Second Hospital of Hebei Medical University Recruiting
Shijiazhuang, Hebei, China, 050000
Contact: Bao-Jun Zhou, M.M    0086-136-0311-7586    zhoubaojun67@hotmail.com   
Contact: Shao-Wei Ma, M.M    0086-137-3331-4055    13733314055@163.com   
Principal Investigator: Bao-Jun Zhou, M.M         
Hebei Medical University Fourth Hospital Recruiting
Shijiazhuang, Hebei, China, 050011
Contact: Yong Li, M.D    0086-311-8609-5678    li_yong_hbth@126.com   
Contact: Qing-Wei Liu, M.M    0086-159-3105-9506    liuqingwei_10@163.com   
Principal Investigator: Yong Li, M.D         
China, Heilongjiang
Harbin Medical University Cancer Hospital Recruiting
Harbin, Heilongjiang, China, 150081
Contact: Kuan Wang, M.D    0086-139-3624-3918    88008008@sina.com   
Contact: Guan-Yu Zhu, M.D    0086-187-4612-6777    zhuguanyu001@163.com   
Principal Investigator: Kuan Wang, M.D         
China, Henan
Henan Cancer Hospital Recruiting
Zhengzhou, Henan, China, 450008
Contact: Guang-Sen Han    0086-138-0381-8006    hnhanguangsen@126.com   
Contact: Wei Yang, M.M    0086-151-3893-9753    294859420@qq.com   
Principal Investigator: Guang-Sen Han         
China, Hubei
Wuhan Union Hospital, China Recruiting
Wuhan, Hubei, China, 430030
Contact: Kai-Xiong Tao, M.D    0086-135-0715-5452    tao_kaixiong@163.com   
Contact: Ke Wu, M.D    0086-135-4524-8289    wuke201288@126.com   
Principal Investigator: Kai-Xiong Tao, M.D         
China, Hunan
The second Xiangya Hospital of Central South University Recruiting
Changsha, Hunan, China, 410011
Contact: Hong-Liang Yao, M.D    0086-138-0845-2603    Yaohl0326@163.com   
Contact: San-Lin Lei, M.D    0086-139-7499-1477    13974991477@163.com   
Principal Investigator: Hong-Liang Yao, M.D         
China, Tianjin
Tianjin Medical University Cancer Institute and Hospital Recruiting
Tianjin, Tianjin, China, 300060
Contact: Han Liang, M.M    0086-130-1138-3125    tjlianghan@126.com   
Contact: Xue-Jun Wang, M.D    0086-    wxjsimon@163.com   
Principal Investigator: Han Liang, M.M         
China, Zhejiang
Zhejiang Cancer Hospital Recruiting
Hanzhou, Zhejiang, China, 310022
Contact: Xin-Bao Wang, M.D    0086-139-0652-3036    wangxb@zjcc.org.cn   
Contact: Chao Hu, M.D    0086-137-3589-3334    huchao1987pj@126.com   
Principal Investigator: Xin-Bao Wang, M.D         
Sponsors and Collaborators
Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Tianjin Medical University Cancer Institute and Hospital
Nanfang Hospital of Southern Medical University
Zhejiang Cancer Hospital
The Second Hospital of Hebei Medical University
Chinese PLA General Hospital
Henan Cancer Hospital
Harbin Medical University
Central South University
Guangdong General Hospital
Wuhan Union Hospital, China
Sun Yat-sen University
Hebei Medical University Fourth Hospital
Guangdong Provincial Hospital of Traditional Chinese Medicine
Investigators
Study Director: shuzhong cui, M.D Affiliated Tumor Hospital of Guangzhou Medical University Recruiting

Responsible Party: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
ClinicalTrials.gov Identifier: NCT02356276     History of Changes
Other Study ID Numbers: HIPEC-01
First Posted: February 5, 2015    Key Record Dates
Last Update Posted: October 31, 2017
Last Verified: October 2017

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

Keywords provided by Affiliated Cancer Hospital & Institute of Guangzhou Medical University:
locally advanced gastric cancer
Hyperthermic Intraperitoneal Chemotherapy
radical gastrectomy with D2 lymphadenectomy

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Paclitaxel
Oxaliplatin
Capecitabine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites