Second Line Chemotherapy for S-1 Refractory Advanced Gastric Cancer

Gastric Cancer Clinical Trial

Official title:

Randomized Phase II/III Trial of Second Line Chemotherapy Comparing CPT-11 Monotherapy Versus S-1/CPT-11 Combination for S-1 Refractory Gastric Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00639327
• Other study ID #: JACCRO GC-05
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: March 5, 2008
• Last updated: June 27, 2011
• Start date: March 2008
• Est. completion date: June 2011

Study information

• Verified date: June 2011
• Source: Japan Clinical Cancer Research Organization
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is compare overall survival of the test arm (CPT-11/S-1 combination) to the control arm (CPT-11 alone) in the subjects with S-1 refractory advanced gastric cancer.

Description:

Standard chemotherapy for advanced gastric cancer (AGC) in the US is Cisplatin/5-FU (CF) or docetaxel/CF (DCF), is in Europe epirubicin/CF (ECF) or epirubicin/oxaliplatin/ capecitabine (EOX). Until 2006, there was no evidence of standard chemotherapy for AGC in Japan. In 2007, by the results of JCOG9912 trial (5-FU alone vs. CPT-11/CDDP vs S-1) and SPIRITS trial (S-1 alone vs. S-1/CDDP), S-1/CDDP is regarded as a new standard regimen in Japan. In 2008, by the results of TOP-002 trial (s-1 alone vs. S-1/CPT-11), S-1/CPT-11 could not show the superiority to S-1 alone. One of the other phase III trials, JACCRO GC-03 trial (S-1 alone vs. S-1/docetaxel, NCT00287768) is now ongoing. However, the position of CPT-11 in the treatment of AGC will be regarded as a second-line.

In Japan there is a controversy for the treatment of S-1 refractory gastric cancer. The controversy is continuing S-1 (like FOLFOX to FOLFIRI) or not as a second-line. After the successful adjuvant S-1 results (ACTS-GC trial), the same problem will occur in the patients who are recurrent from adjuvant S-1.

Then, we conducted a phase II/III trial of CPT-11 with or without S-1 in the treatment of first-line S-1 refractory AGC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: June 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Histologically proven inoperable advanced gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) or relapse gastric adenocarcinoma

• Subjects must be able to take orally

• Subjects must be confirmed to be PD status by picture diagnosis after first-line chemotherapy using S-1 alone, S-1 + Cisplatinum or S-1 + taxane, except S-1 + CPT-11

• Within 4 weeks from the diagnosis of PD

• Total dosage of S-1 at the first-line is over 2,240mg/m2 in S-1 alone treatment, 1,680mg/m2 in the S-1 combination

• ECOG performance status = 1

• Follow up Age 20 or over

• Life expectancy estimated more than 12 weeks

• Hgb = 8 g/dL, WBC 4,000-12,000/mm3, ANC = 2,000/mm3, platelets = 100,000/mm3

• Creatinine = upper normal limit (UNL)

• Total bilirubin = 1.5 X UNL

• Written informed consent

Exclusion Criteria:

• S-1 + CPT-11 was employed as a first-line

• Any other cytotoxic agents therapy, immuno-therapy, radiation-therapy

• After S-1 adjuvant

• Suspended cases by adverse events by S-1 or S-1 combination

• Excessive amounts of ascites require drainage

• Known brain metastases

• History of hypersensitivity to fluoropyrimidines and CPT-11

• Pregnancy or lactation women, or women with suspected pregnancy or men with willing to get pregnant

• Active double cancer

• Gastrointestinal bleeding

• Any subject judged by the investigator to be unfit for any reason to participate in the study

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• S-1 + irinotecan
Irinotecan 150mg/m2 iv on day one and S-1 po days 1 to 14 every 3 weeks until PD
• irinotecan
Irinotecan 150mg/m2 iv on day one every two weeks until PD

Locations

Country	Name	City	State
Japan	Aichi Medical University Hospital	Aichi
Japan	Nakadoori General Hospital	Akita
Japan	Aomori Prefectural Central Hospital	Aomori
Japan	Asahikawa Medical College Department Medicine	Asahikawa	Hokkaido
Japan	Asahikawa Medical College Hospital	Asahikawa	Hokkaido
Japan	Nippon Medical School	Bunkyo-ku	Tokyo
Japan	ChibaUniversity Hospital	Chiba
Japan	Surugadai Nihon University Hospital	Chiyoda-ku	Tokyo
Japan	Fukui Red Cross Hospital	Fukui
Japan	Saiseikai Hospital	Fukui
Japan	Kyusyu University Faculty of Medical Sciences	Fukuoka
Japan	National Hospital Organization Kyushu Medical Center	Fukuoka
Japan	National Kyusyu Cancer Center	Fukuoka
Japan	Saiseikai Fukuoka General Hospital	Fukuoka
Japan	Fukushima Medical University	Fukushima
Japan	Fukuyama City Hospital	Fukuyama	Hiroshima
Japan	Gifu Municipal Hospital	Gifu
Japan	Gifu Prefectural General Medical Center	Gifu
Japan	Graduate School of Medicine, Gifu University	Gifu
Japan	Hakodate Goryoukaku Hopsital	Hakodate	Hokkaido
Japan	Hirosahi University Graduate School of Medicine	Hirosaki	Aomori
Japan	Hiroshima University Hospital	Hiroshima
Japan	Hiroshima University Research Institute for Radiation Biology and Medicine Tumor Surgery	Hiroshima
Japan	Tokai University Hospital	Isehara	Kanagawa
Japan	Nihon University Itabashi Hospital	Itabashi-ku	Tokyo
Japan	Teikyo University Hospital	Itabashi-ku	Tokyo
Japan	Rinku General Medical Center	Izumisano	Osaka
Japan	Shimane University Faculty of Medicine	Izumo	Shimane
Japan	National Hospital Organization Kagoshima Medical Center	Kagoshima
Japan	Ishikawa Prefectural Central Hospital	Kanazawa	Ishikawa
Japan	Kanazawa Medical University Hospital	Kawakita	Ishikawa
Japan	St.Marianna University School Of Medicine Hospital	Kawasaki	Kanagawa
Japan	Kagawa Medical University Hospital	Kida	Kagawa
Japan	Kimen Municipal Hospital	Kimen	Osaka
Japan	Kirishima Medical Center	Kirishima	Kagoshima
Japan	Nippon Steel Yawata Memorial Hospital	Kitakyusyu	Fukuoka
Japan	Kochi Health Sciences Center	Kochi
Japan	Kumamoto Medical University Hospital	Kumamoto
Japan	Kurume University Hospital	Kurume	Fukuoka
Japan	Gunma University Hospital	Maehashi	Gunma
Japan	Kaneda Hospital	Maniwa	Okayama
Japan	Matsue City Hospital	Matsue	Shimane
Japan	Toho University Ohhashi Medical Center	Meguro-ku	Tokyo
Japan	International University of Health and Welfare Mita Hospital	Minato-ku	Tokyo
Japan	The Jikei University	Minato-ku	Tokyo
Japan	Toranomon Hospital	Minato-ku	Tokyo
Japan	Iwate Medical University Hospital	Morioka	Iwate
Japan	Iwate Prefectural Central Hospital	Morioka	Iwate
Japan	Nagano Municipal Hospital	Nagano
Japan	Midori Municipal Hospital	Nagoya	Aichi
Japan	Nagoya City University Hospital	Nagoya	Aichi
Japan	Miyagi Cancer Center	Natori	Miyagi
Japan	Niigata Prefectural Cancer Center	Niigata
Japan	Yamamoto Hospital	Noshiro	Akita
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	Gunma Prefectural Cancer Center	Oota	Gunma
Japan	Toho University Omori Medical Center	Oota-ku	Tokyo
Japan	Kitano Hospital	Osaka
Japan	Osaka City University Graduate School of Medicine	Osaka
Japan	Osaka General Medical Center	Osaka
Japan	Osaka Koseinenkin Hospital	Osaka
Japan	Saiseikai Shiga Hospital	Ritto	Shiga
Japan	Saga Prefectural Hospital Kouseikan	Saga
Japan	Osaka Rosai Hospital	Sakai	Osaka
Japan	Sakai Municipal Hospital	Sakai	Osaka
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido
Japan	Sapporo Medical University Hospital	Sapporo	Hokkaido
Japan	Institute of Development,Aging and Cancer,Tohoku University	Sendai	Miyagi
Japan	Sendai Medical Center	Sendai	Miyagi
Japan	Tohoku University School Of Medicine	Sendai	Miyagi
Japan	Dokkyo University School of Medecine	Shimotsuga	Tochigi
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Japan	Tokyo Women's Medical University Institute of Gastorenterology	Shinjuku-ku	Tokyo
Japan	Suita Municipal Hospital Website	Suita	Osaka
Japan	Metropolitan Bokutoh Hospital	Sumida-ku	Tokyo
Japan	Hyogo Prefectural Awaji Hospital	Sumoto	Hyogo
Japan	Kouseiren Takaoka Hospital	Takaoka	Toyama
Japan	Saiseikai Takaoka Hospital	Takaoka	Toyama
Japan	Toyama Prefectural Center Hospital	Toyama
Japan	Yamagata University Faculty Of Medicine	Yamagata
Japan	Yao City Hospital	Yao	Osaka
Japan	Citizen's General Medical Center attached to Yokohama City University	Yokohama	Kanagawa
Japan	Showa University Fujigaoka Hospital	Yokohama	Kanagawa
Japan	Showa University Northern Yokohama Hospital	Yokohama	Kanagawa
Japan	Tottori University Faculty of Medicine	Yonago	Tottori
Japan	University of Fukui Faculty of Medical Scieneces Hospital	Yoshida-gun	Fukui

Sponsors (2)

Lead Sponsor	Collaborator
Japan Clinical Cancer Research Organization	Taiho Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In phase II part, progressive disease rate will be measured for the safety. In phase III part, overall survival will be measured for the benefit of doublet.		Phase II: 6 weeks from treatment, Phase III: 2 years OS from randomization	Yes
Secondary	Adverse events, response rates, progression free survival, time to treatment failure, change over rates to 3rd line		2 years	Yes