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

Gastric Cancer Clinical Trial

— EHTLAGCRGD2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02356276
• Other study ID #: HIPEC-01
• Status: Recruiting
• Phase: Phase 3
• First received: January 29, 2015
• Last updated: October 29, 2017
• Start date: May 11, 2015
• Est. completion date: January 2022

Study information

• Verified date: October 2017
• Source: Affiliated Tumor Hospital of Guangzhou Medical University
• Contact: shuzhong cui, M.D
• Phone: 0086-138-0251-3800
• Email: cuishuzhong[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 584
• Est. completion date: January 2022
• Est. primary completion date: January 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Procedure:
• D2 lymphadenectomy

• 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.

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.

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing	Beijing
China	The second Xiangya Hospital of Central South University	Changsha	Hunan
China	Affiliated Tumor Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Guangdong Provincial Hospital of Traditional Chinese Medicine	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital	Hanzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Hebei Medical University Fourth Hospital	Shijiazhuang	Hebei
China	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Wuhan Union Hospital, China	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (14)

Lead Sponsor

Collaborator

Affiliated Tumor Hospital of Guangzhou Medical University

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CEA mRNA expression of peritoneal lavage fluid	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
Primary	5-year overall survival	assess overall survival during 5 years in both study arms	5 years
Secondary	5-year progression-free survival	assess progression-free survival rate during 5 years in both study arms	5 years
Secondary	liver metastatic rate	calculate the percent of liver metastatic in both two arms during 5 years	5 years
Secondary	local recurrence rate	calculate the percent of local recurrence in both two arms during 5 years	5 years
Secondary	side effects	determine percent of adverse events or side effects according to NCI criteria, Common Terminology Criteria for AE (CTCAE 4.0).	5 years