Gastric Cancer
Conditions
Keywords
Stomach Neoplasms, Second line chemotherapy, Refractory to S-1, irinotecan, S-1 and Irinotecan Combination, Phase III study
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.
Interventions
DRUGS-1 + irinotecan
Irinotecan 150mg/m2 iv on day one and S-1 po days 1 to 14 every 3 weeks until PD
DRUGirinotecan
Irinotecan 150mg/m2 iv on day one every two weeks until PD
Sponsors
Taiho Pharmaceutical Co., Ltd.
Japan Clinical Cancer Research Organization
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| Adverse events, response rates, progression free survival, time to treatment failure, change over rates to 3rd line | 2 years |
Countries
Japan
Outcome results
None listed