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

• ClinicalTrials.gov Identifier: NCT02356276
• Recruitment Status: Unknown
• First Posted: February 5, 2015
• Last Update Posted: October 31, 2017
• Sponsor: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• 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 Provincial People's 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

Tracking Information

• First Submitted Date: January 29, 2015
• First Posted Date: February 5, 2015
• Last Update Posted Date: October 31, 2017
• Actual Study Start Date: May 11, 2015
• Estimated Primary Completion Date: January 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 29, 2017)

5-year overall survival [ Time Frame: 5 years ]

assess overall survival during 5 years in both study arms

• Original Primary Outcome Measures (submitted: February 4, 2015): 5-year survival [ Time Frame: 5 years ]

Current Secondary Outcome Measures (submitted: October 29, 2017)

• 5-year progression-free survival [ Time Frame: 5 years ]
  assess progression-free survival rate during 5 years in both study arms
• liver metastatic rate [ Time Frame: 5 years ]
  calculate the percent of liver metastatic in both two arms during 5 years
• local recurrence rate [ Time Frame: 5 years ]
  calculate the percent of local recurrence in both two arms during 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).

Original Secondary Outcome Measures (submitted: February 4, 2015)

• progression-free survival [ Time Frame: 5 years ]
• liver metastatic rate [ Time Frame: 5 years ]
• local recurrence rate [ Time Frame: 5 years ]
• side effects [ Time Frame: 5 years ]

Current Other Pre-specified Outcome Measures (submitted: October 29, 2017)

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

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of HIPEC in the Treatment of Locally Advanced Gastric Cancer After radIcal Gastrectomy With D2
• Official Title: A Phase III Study of Hyperthermic Intraperitoneal Chemotherapy in the Treatment of Locally Advanced Gastric Cancer After radIcal Gastrectomy With D2
• 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.

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Gastric Cancer

Intervention

• 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

Study Arms

• 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.

  Interventions:

  • Procedure: D2 lymphadenectomy
  • Procedure: Hyperthermic Intraperitoneal Chemotherapy
  • Drug: Systemic chemotherapy (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.

  Interventions:

  • Procedure: D2 lymphadenectomy
  • Drug: Systemic chemotherapy (XELOX or SOX regimens)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: February 4, 2015): 584
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2022
• Estimated Primary Completion Date: January 2022 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02356276
• Other Study ID Numbers: HIPEC-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• Original Responsible Party: Same as current
• Current Study Sponsor: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• Original Study Sponsor: Same as current

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 Provincial People's 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

• PRS Account: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
• Verification Date: October 2017