Clinical trial NCT00639327: Second Line Chemotherapy for S-1 Refractory Advanced Gastric Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Gastric Cancer
Keywords: Stomach Neoplasms
Second line chemotherapy
Refractory to S-1
irinotecan
S-1 and Irinotecan Combination
Phase III study
Lead sponsor: Japan Clinical Cancer Research Organization
Sponsor class: OTHER
Collaborators: name: Taiho Pharmaceutical Co., Ltd.
First posted: 2008-03-20
Enrollment: 300
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Phase II: 6 weeks from treatment, Phase III: 2 years OS from randomization
Secondary outcomes:
measure: Adverse events, response rates, progression free survival, time to treatment failure, change over rates to 3rd line
timeFrame: 2 years
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Midori Municipal Hospital
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Noshiro
country: Japan
facility: Yamamoto Hospital
state: Akita
city: Hirosaki
country: Japan
facility: Hirosahi University Graduate School of Medicine
state: Aomori
city: Yoshida-gun
country: Japan
facility: University of Fukui Faculty of Medical Scieneces Hospital
state: Fukui
city: Kitakyusyu
country: Japan
facility: Nippon Steel Yawata Memorial Hospital
state: Fukuoka
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Maehashi
country: Japan
facility: Gunma University Hospital
state: Gunma
city: Oota
country: Japan
facility: Gunma Prefectural Cancer Center
state: Gunma
city: Fukuyama
country: Japan
facility: Fukuyama City Hospital
state: Hiroshima
city: Asahikawa
country: Japan
facility: Asahikawa Medical College Department Medicine
state: Hokkaido
city: Asahikawa
country: Japan
facility: Asahikawa Medical College Hospital
state: Hokkaido
city: Hakodate
country: Japan
facility: Hakodate Goryoukaku Hopsital
state: Hokkaido
city: Sapporo
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
state: Hokkaido
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Sumoto
country: Japan
facility: Hyogo Prefectural Awaji Hospital
state: Hyogo
city: Kanazawa
country: Japan
facility: Ishikawa Prefectural Central Hospital
state: Ishikawa
city: Kawakita
country: Japan
facility: Kanazawa Medical University Hospital
state: Ishikawa
city: Morioka
country: Japan
facility: Iwate Prefectural Central Hospital
state: Iwate
city: Morioka
country: Japan
facility: Iwate Medical University Hospital
state: Iwate
city: Kida
country: Japan
facility: Kagawa Medical University Hospital
state: Kagawa
city: Kirishima
country: Japan
facility: Kirishima Medical Center
state: Kagoshima
city: Isehara
country: Japan
facility: Tokai University Hospital
state: Kanagawa
city: Kawasaki
country: Japan
facility: St.Marianna University School Of Medicine Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Showa University Northern Yokohama Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Showa University Fujigaoka Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Citizen's General Medical Center attached to Yokohama City University
state: Kanagawa
city: Natori
country: Japan
facility: Miyagi Cancer Center
state: Miyagi
city: Sendai
country: Japan
facility: Institute of Development,Aging and Cancer,Tohoku University
state: Miyagi
city: Sendai
country: Japan
facility: Tohoku University School Of Medicine
state: Miyagi
city: Sendai
country: Japan
facility: Sendai Medical Center
state: Miyagi
city: Maniwa
country: Japan
facility: Kaneda Hospital
state: Okayama
city: Izumisano
country: Japan
facility: Rinku General Medical Center
state: Osaka
city: Kimen
country: Japan
facility: Kimen Municipal Hospital
state: Osaka
city: Sakai
country: Japan
facility: Sakai Municipal Hospital
state: Osaka
city: Sakai
country: Japan
facility: Osaka Rosai Hospital
state: Osaka
city: Suita
country: Japan
facility: Suita Municipal Hospital Website
state: Osaka
city: Yao
country: Japan
facility: Yao City Hospital
state: Osaka
city: Ritto
country: Japan
facility: Saiseikai Shiga Hospital
state: Shiga
city: Izumo
country: Japan
facility: Shimane University Faculty of Medicine
state: Shimane
city: Matsue
country: Japan
facility: Matsue City Hospital
state: Shimane
city: Shimotsuga
country: Japan
facility: Dokkyo University School of Medecine
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Nippon Medical School
state: Tokyo
city: Chiyoda-ku
country: Japan
facility: Surugadai Nihon University Hospital
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Teikyo University Hospital
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Nihon University Itabashi Hospital
state: Tokyo
city: Meguro-ku
country: Japan
facility: Toho University Ohhashi Medical Center
state: Tokyo
city: Minato-ku
country: Japan
facility: Toranomon Hospital
state: Tokyo
city: Minato-ku
country: Japan
facility: The Jikei University
state: Tokyo
city: Minato-ku
country: Japan
facility: International University of Health and Welfare Mita Hospital
state: Tokyo
city: Oota-ku
country: Japan
facility: Toho University Omori Medical Center
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University Institute of Gastorenterology
state: Tokyo
city: Sumida-ku
country: Japan
facility: Metropolitan Bokutoh Hospital
state: Tokyo
city: Yonago
country: Japan
facility: Tottori University Faculty of Medicine
state: Tottori
city: Takaoka
country: Japan
facility: Saiseikai Takaoka Hospital
state: Toyama
city: Takaoka
country: Japan
facility: Kouseiren Takaoka Hospital
state: Toyama
city: Aichi
country: Japan
facility: Aichi Medical University Hospital
city: Akita
country: Japan
facility: Nakadoori General Hospital
city: Aomori
country: Japan
facility: Aomori Prefectural Central Hospital
city: Chiba
country: Japan
facility: ChibaUniversity Hospital
city: Fukui
country: Japan
facility: Fukui Red Cross Hospital
city: Fukui
country: Japan
facility: Saiseikai Hospital
city: Fukuoka
country: Japan
facility: Saiseikai Fukuoka General Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center
city: Fukuoka
country: Japan
facility: National Kyusyu Cancer Center
city: Fukuoka
country: Japan
facility: Kyusyu University Faculty of Medical Sciences
city: Fukushima
country: Japan
facility: Fukushima Medical University
city: Gifu
country: Japan
facility: Gifu Municipal Hospital
city: Gifu
country: Japan
facility: Gifu Prefectural General Medical Center
city: Gifu
country: Japan
facility: Graduate School of Medicine, Gifu University
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Research Institute for Radiation Biology and Medicine Tumor Surgery
city: Kagoshima
country: Japan
facility: National Hospital Organization Kagoshima Medical Center
city: Kochi
country: Japan
facility: Kochi Health Sciences Center
city: Kumamoto
country: Japan
facility: Kumamoto Medical University Hospital
city: Nagano
country: Japan
facility: Nagano Municipal Hospital
city: Niigata
country: Japan
facility: Niigata Prefectural Cancer Center
city: Okayama
country: Japan
facility: National Hospital Organization Okayama Medical Center
city: Osaka
country: Japan
facility: Kitano Hospital
city: Osaka
country: Japan
facility: Osaka City University Graduate School of Medicine
city: Osaka
country: Japan
facility: Osaka Koseinenkin Hospital
city: Osaka
country: Japan
facility: Osaka General Medical Center
city: Saga
country: Japan
facility: Saga Prefectural Hospital Kouseikan
city: Toyama
country: Japan
facility: Toyama Prefectural Center Hospital
city: Yamagata
country: Japan
facility: Yamagata University Faculty Of Medicine
Study officials:
affiliation: Surugadai Nihon University Hospital
name: Masashi Fujii, M.D.,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.