Intraperitoneal Chemotherapy and Systemic Chemotherapy Versus Systemic Chemotherapy After Curative Resection of Serosa-positive Gastric Cancer (EPIC-GC)

Prospective Randomized Multicenter Phase III Trial of Intraperitoneal Chemotherapy and Systemic Chemotherapy Versus Systemic Chemotherapy After Curative Resection of Serosa-positive Gastric Cancer

Intraperitoneal chemotherapy as an adjuvant treatment modality is designed to eradicate intraperitoneal free tumor cells that can be a source of peritoneal carcinomatosis. Although we have not reached unanimous consensus, favorable reports on the outcome of intraperitoneal chemotherapy have been published.

In this study, we review the clinicopathological characteristics of patients and effects of early postoperative intraperitoneal chemotherapy (EPIC) on overall and gastric cancer-specific survival and patterns of recurrence of gastric cancer patients with macroscopic serosal invasion.

The aim of this study is to evaluate the impact of intraperitoneal chemotherapy on overall and disease free survival of advanced gastric cancer patients with serosal invasion after potentially curative surgery.

Study Overview

• Status: Unknown
• Conditions: Advanced Gastric Cancer With Serosal Invasion
• Intervention / Treatment: Procedure: surgery; Drug: adjuvant systemic chemotherapy; Drug: Early postoperative intraperitoneal chemothgerapy

• Study Type: Interventional
• Enrollment (Anticipated): 230
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of, 702-210
    • Recruiting
    • Kyungpook National University Medical Center Gastric Cancer Center
    • Contact: Wansik Yu, MD, PhD; Phone Number: 82-53-200-2700; Email: wyu@nknu.ac.kr
    • Principal Investigator: Wansik Yu, MD, PhD
    • Sub-Investigator: Oh Kyoung Kwon, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. histologically proven adenocarcinoma of the stomach
2. preoperative suspicion of serosal invasion on the radiological examination
3. candidate for curative resection of the stomach with D2
4. age from 19 to 70 year old
5. Eastern Cooperative Oncology Group Performance status :0, 1, or 2
6. absolute neutrophil count≥1,500/microliter, hemoglobin≥9.0g/dL, and platelet≥100,000/microliter
7. serum Creatinine<1.5mg/dL
8. total bilirubin <2 x upper normal limit, transaminase<3 x upper normal limit
9. patients without previous administration of chemotherapeutic agent
10. patients who agreed and signed to the informed consent form

Exclusion Criteria:

1. malignancy of the stomach except for adenocarcinoma
2. history of hypersensitivity to 5-fluorouracil or mitomycin
3. concomitant infectious disease
4. active hepatitis or chronic liver disease
5. history of psychotic disorders
6. patients with disorders in the central nervous system
7. history of other malignancy within 5 years
8. history of clinically significant heart disease (congestive heart failure, symptomatic coronary artery disease, symptomatic arrhythmia, myocardial infarction)
9. patients with increased bleeding tendency
10. pregnant or lactating female patients
11. patient who did not agreed and signed to the informed consent form

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; curative resection of the stomach with D2 plus intraperitoneal chemotherapy plus adjuvant systemic chemotherapy with S-1	Procedure: surgery; Total or subtotal gastrectomy with D2; Drug: adjuvant systemic chemotherapy; adjuvant systemic chemotherapy with S-1 (<1.25m2:40mg, 1.25-1.5m2:50mg, >1.5m2:60mg, bid); Drug: Early postoperative intraperitoneal chemothgerapy; operation day: 0.9％ saline solution 1L plus mitomycin C 10 mg/m2 1 - 4 postoprative day: 0.9％ saline solution 1L plus 5-FU 700 mg/m2 plus sodium bicarbonate 50 mEq
Placebo Comparator: Arm B; curative resection of the stomach with D2 plus adjuvant systemic chemotherapy with S-1	Procedure: surgery; Total or subtotal gastrectomy with D2; Drug: adjuvant systemic chemotherapy; adjuvant systemic chemotherapy with S-1 (<1.25m2:40mg, 1.25-1.5m2:50mg, >1.5m2:60mg, bid)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relapsed free survival	during regular follow-up with blood test, radiologic, endoscopic surveillance patients with recurrence will be detected and recorded	postoperative 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	during regular follow-up with blood test, radiologic, endoscopic surveillance patients with recurrence will be detected and recorded	postoperative 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
surgery and intraperitoneal chemotherapy-related morbidity and mortality	In hospital complication related to surgery or intraperitoneal chemotherapy will be recored and analyzed to evaluate the safety of intraperitoneal chemotherapy.	postoperative 30days

Collaborators and Investigators

• Sponsor: Kyungpook National University Hospital
• Collaborators: National Cancer Center, Korea; Chonnam National University Hospital; Daegu Catholic University Medical Center; Chung-Ang University Hosptial, Chung-Ang University College of Medicine; Hanyang University; Yeungnam University Hospital; Severance Hospital; Keimyung University Dongsan Medical Center; Dong-A University Hospital; Korea Cancer Center Hospital
• Investigators: Principal Investigator: Wansik Yu, MD. PhD, Kyungpook National University Medical Center

Publications and helpful links

General Publications

• 1. Maruyama K, Okabayashi K, Kinoshita T. Progress in gastric cancer surgery in Japan and its limits of radicality. World J Surg 1987;11:418-425. 2. Lee JL, Kang HJ, Kang YK, et al. Phase I/II study of 3-week combination of S-1 and cisplatin chemotherapy for metastatic or recurent gastric cancer. Cancer Chemother Pharmacol 2007 (E-pub). 3. Schoffski P. The modulated oral fluoropyrimidine prodrug S-1, and its use in gastrointestinal cancer and other solid tumors. Anticancer Drug 2004;15:85-106. 4. Sugimachi K, Maehara Y, Horikoshi N et al. An early phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. Oncology 1999;57:202-210. 5. Koizumi W, Kurihara M, Nakajo S et al. Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. Oncology 2000;58:191-197. 6. Sakata Y, Ohtsu A, Horikoshi N et al. Late phase II study of novel oral fluoropyrimidine anticancer drugs S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients. Eur J Cancer 1998;34:1715-1720. 7. Nagashima F, Ohtsu A, Yoshida S et al. Japanese nationwide postmarketing survey of S-1 in patients with advanced gastric cancer. Gastric Cancer 2005;8:6-11. 8. Chollet P, Schoffski P, Weigang-Kohler K et al. Phase II trial with S-1 in chemotherapy-naïve patients with gastric cancer. A trial performed by the EORTC early clinical studies group (ECGC). Eur J Cancer 2003;39:1264-1270. 9. Ilson D. Just when you thought the fluorouracil debate was over: S-1 and gastric cancer. J Clin Oncol 2005;23:6826-6828. 10. Hoff PM, Saad ED, Ajani JA et al. Phase I study with pharmacokinetics of S-1, an oral daily schedule for 28 days in patients with solid tumors. Clin Cancer Res 2003;9:134-142. 11. Simon R. Optimal two-stage design for phase II clinical trials. Controlled Clin Trials 1989;10:1-10.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): November 1, 2018

Study Registration Dates

• First Submitted: July 26, 2014
• First Submitted That Met QC Criteria: July 29, 2014
• First Posted (Estimate): July 31, 2014

Study Record Updates

• Last Update Posted (Estimate): July 31, 2014
• Last Update Submitted That Met QC Criteria: July 29, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: advanced gastric cancer; serosal invasion; peritoneal recurrence; intraperitoneal chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: EPIC-GC; KNUMCGCC-001 (Other Identifier: KNUMC)