Second Line Chemotherapy for S-1 Refractory Advanced Gastric Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: S-1 + irinotecan; Drug: irinotecan

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 480-1195
    • Aichi Medical University Hospital
  • Akita, Japan, 010-8577
    • Nakadoori General Hospital
  • Aomori, Japan, 030-8553
    • Aomori Prefectural Central Hospital
  • Chiba, Japan, 260-8677
    • ChibaUniversity Hospital
  • Fukui, Japan, 918-8501
    • Fukui Red Cross Hospital
  • Fukui, Japan, 918-8503
    • Saiseikai Hospital
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center
  • Fukuoka, Japan, 810-0001
    • Saiseikai Fukuoka General Hospital
  • Fukuoka, Japan, 811-1395
    • National Kyusyu Cancer Center
  • Fukuoka, Japan, 812-8582
    • Kyusyu University Faculty of Medical Sciences
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University
  • Gifu, Japan, 500-8717
    • Gifu Prefectural General Medical Center
  • Gifu, Japan, 500-8513
    • Gifu Municipal Hospital
  • Gifu, Japan, 501-1193
    • Graduate School of Medicine, Gifu University
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Hiroshima, Japan, 734-8553
    • Hiroshima University Research Institute for Radiation Biology and Medicine Tumor Surgery
  • Kagoshima, Japan, 892-0853
    • National Hospital Organization Kagoshima Medical Center
  • Kochi, Japan, 781-8555
    • Kochi Health Sciences Center
  • Kumamoto, Japan, 860-8556
    • Kumamoto Medical University Hospital
  • Nagano, Japan, 381-0006
    • Nagano Municipal Hospital
  • Niigata, Japan, 951-8566
    • Niigata Prefectural Cancer Center
  • Okayama, Japan, 701-1192
    • National Hospital Organization Okayama Medical Center
  • Osaka, Japan, 558-8558
    • Osaka General Medical Center
  • Osaka, Japan, 530-8480
    • Kitano Hospital
  • Osaka, Japan, 545-8585
    • Osaka City University Graduate School of Medicine
  • Osaka, Japan, 553-0003
    • Osaka Koseinenkin Hospital
  • Saga, Japan, 840-8571
    • Saga Prefectural Hospital Kouseikan
  • Toyama, Japan, 930-8550
    • Toyama Prefectural Center Hospital
  • Yamagata, Japan, 990-9585
    • Yamagata University Faculty of Medicine
  • Aichi
    • Nagoya, Aichi, Japan, 467-8602
      • Nagoya City University Hospital
    • Nagoya, Aichi, Japan, 458-0037
      • Midori Municipal Hospital
  • Akita
    • Noshiro, Akita, Japan, 016-0014
      • Yamamoto Hospital
  • Aomori
    • Hirosaki, Aomori, Japan, 036-8562
      • Hirosahi University Graduate School of Medicine
  • Fukui
    • Yoshida-gun, Fukui, Japan, 910-1193
      • University of Fukui Faculty of Medical Scieneces Hospital
  • Fukuoka
    • Kitakyusyu, Fukuoka, Japan, 805-8508
      • Nippon Steel Yawata Memorial Hospital
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Gunma
    • Maehashi, Gunma, Japan, 371-0034
      • Gunma University Hospital
    • Oota, Gunma, Japan, 373-8550
      • Gunma Prefectural Cancer Center
  • Hiroshima
    • Fukuyama, Hiroshima, Japan, 721-8511
      • Fukuyama City Hospital
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 078-8510
      • Asahikawa Medical College Department Medicine
    • Asahikawa, Hokkaido, Japan, 078-8510
      • Asahikawa Medical College Hospital
    • Hakodate, Hokkaido, Japan, 040-0001
      • Hakodate Goryoukaku Hopsital
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center
    • Sapporo, Hokkaido, Japan, 060-8543
      • Sapporo Medical University Hospital
  • Hyogo
    • Sumoto, Hyogo, Japan, 656-0017
      • Hyogo Prefectural AWAJI Hospital
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8530
      • Ishikawa Prefectural Central Hospital
    • Kawakita, Ishikawa, Japan, 920-0293
      • Kanazawa Medical University Hospital
  • Iwate
    • Morioka, Iwate, Japan, 020-0066
      • Iwate Prefectural Central Hospital
    • Morioka, Iwate, Japan, 020-8505
      • Iwate Medical University Hospital
  • Kagawa
    • Kida, Kagawa, Japan, 761-0793
      • Kagawa Medical University Hospital
  • Kagoshima
    • Kirishima, Kagoshima, Japan, 899-5112
      • Kirishima Medical Center
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Tokai University Hospital
    • Kawasaki, Kanagawa, Japan, 216-8511
      • St.Marianna University School of Medicine hospital
    • Yokohama, Kanagawa, Japan, 224-8503
      • Showa University Northern Yokohama Hospital
    • Yokohama, Kanagawa, Japan, 227-8501
      • Showa University Fujigaoka Hospital
    • Yokohama, Kanagawa, Japan, 232-0024
      • Citizen's General Medical Center attached to Yokohama City University
  • Miyagi
    • Natori, Miyagi, Japan, 981-1293
      • Miyagi Cancer Center
    • Sendai, Miyagi, Japan, 980-8574
      • Institute of Development,Aging and Cancer,Tohoku University
    • Sendai, Miyagi, Japan, 980-8574
      • Tohoku University School of Medicine
    • Sendai, Miyagi, Japan, 983-8520
      • Sendai Medical Center
  • Okayama
    • Maniwa, Okayama, Japan, 719-3105
      • Kaneda Hospital
  • Osaka
    • Izumisano, Osaka, Japan, 598-0048
      • Rinku General Medical Center
    • Kimen, Osaka, Japan, 562-8562
      • Kimen Municipal Hospital
    • Sakai, Osaka, Japan, 590-0064
      • Sakai Municipal Hospital
    • Sakai, Osaka, Japan, 591-8025
      • Osaka Rosai Hospital
    • Suita, Osaka, Japan, 564-0082
      • Suita Municipal Hospital Website
    • Yao, Osaka, Japan, 581-0069
      • Yao City Hospital
  • Shiga
    • Ritto, Shiga, Japan, 520-3046
      • Saiseikai Shiga Hospital
  • Shimane
    • Izumo, Shimane, Japan, 693-8501
      • Shimane University Faculty of Medicine
    • Matsue, Shimane, Japan, 690-8509
      • Matsue City Hospital
  • Tochigi
    • Shimotsuga, Tochigi, Japan, 321-0293
      • Dokkyo University School of Medecine
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Nippon Medical School
    • Chiyoda-ku, Tokyo, Japan, 101-8309
      • Surugadai Nihon university hospital
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Nihon University Itabashi Hospital
    • Itabashi-ku, Tokyo, Japan, 173-8606
      • Teikyo University Hospital
    • Meguro-ku, Tokyo, Japan, 153-8515
      • Toho University Ohhashi Medical Center
    • Minato-ku, Tokyo, Japan, 105-8470
      • Toranomon Hospital
    • Minato-ku, Tokyo, Japan, 105-8471
      • The Jikei University
    • Minato-ku, Tokyo, Japan, 108-8329
      • International University of Health and Welfare MITA Hospital
    • Oota-ku, Tokyo, Japan, 143-8541
      • Toho University Omori Medical Center
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio University Hospital
    • Shinjuku-ku, Tokyo, Japan, 162-8666
      • Tokyo Women's Medical University Institute of Gastorenterology
    • Sumida-ku, Tokyo, Japan, 130-8575
      • Metropolitan Bokutoh Hospital
  • Tottori
    • Yonago, Tottori, Japan, 683-8504
      • Tottori University Faculty of Medicine
  • Toyama
    • Takaoka, Toyama, Japan, 933-8525
      • Saiseikai Takaoka Hospital
    • Takaoka, Toyama, Japan, 933-8555
      • Kouseiren Takaoka Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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
Experimental: A; CPT-11+ S-1	Drug: S-1 + irinotecan; Irinotecan 150mg/m2 iv on day one and S-1 po days 1 to 14 every 3 weeks until PD; Other Names: CPT-11; TS-1
Active Comparator: B; CPT-11	Drug: irinotecan; Irinotecan 150mg/m2 iv on day one every two weeks until PD; Other Names: CPT-11

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events, response rates, progression free survival, time to treatment failure, change over rates to 3rd line	2 years

Collaborators and Investigators

• Sponsor: Japan Clinical Cancer Research Organization
• Collaborators: Taiho Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Masashi Fujii, M.D.,PhD, Surugadai Nihon university hospital

Publications and helpful links

General Publications

• Tanabe K, Fujii M, Nishikawa K, Kunisaki C, Tsuji A, Matsuhashi N, Takagane A, Ohno T, Kawase T, Kochi M, Yoshida K, Kakeji Y, Ichikawa W, Chin K, Terashima M, Takeuchi M, Nakajima T. Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05). Ann Oncol. 2015 Sep;26(9):1916-1922. doi: 10.1093/annonc/mdv265. Epub 2015 Jun 24.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: March 5, 2008
• First Submitted That Met QC Criteria: March 19, 2008
• First Posted (Estimate): March 20, 2008

Study Record Updates

• Last Update Posted (Estimate): June 28, 2011
• Last Update Submitted That Met QC Criteria: June 27, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: irinotecan; Stomach Neoplasms; Second line chemotherapy; Refractory to S-1; S-1 and Irinotecan Combination; Phase III study
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: JACCRO GC-05