Second Line Chemotherapy for S-1 Refractory Advanced Gastric Cancer

Japan Clinical Cancer Research Organization

Status and phase

Completed

Phase 3

Phase 2

Conditions

Gastric Cancer

Treatments

Drug: S-1 + irinotecan

Drug: irinotecan

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00639327

JACCRO GC-05

Details and patient eligibility

About

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.

Full 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.

Enrollment

300 estimated patients

Sex

All

Ages

20+ years old

Volunteers

No Healthy Volunteers

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