Second Line Chemotherapy for S-1 Refractory Advanced Gastric Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: S-1 + irinotecan
* Drug: irinotecan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>CPT-11+ S-1 | Drug: S-1 + irinotecan<br>* Irinotecan 150mg/m2 iv on day one and S-1 po days 1 to 14 every 3 weeks until PD<br>* Other names: CPT-11;|
| Active Comparator: B<br>CPT-11 | Drug: irinotecan<br>* Irinotecan 150mg/m2 iv on day one every two weeks until PD<br>* Other names: CPT-11;|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stomach Neoplasms, Second line chemotherapy, Refractory to S-1, irinotecan, S-1 and Irinotecan Combination, Phase III study