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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

Phase 2/Phase 3
20 Years
Not Enrolling
Gastric Cancer

Thank you

Trial Information

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

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.

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome 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.

Outcome Time Frame:

Phase II: 6 weeks from treatment, Phase III: 2 years OS from randomization

Safety Issue:


Principal Investigator

Masashi Fujii, M.D.,PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Surugadai Nihon University Hospital


Japan: Ministry of Health, Labor and Welfare

Study ID:




Start Date:

March 2008

Completion Date:

June 2011

Related Keywords:

  • Gastric Cancer
  • Stomach Neoplasms
  • Second line chemotherapy
  • Refractory to S-1
  • irinotecan
  • S-1 and Irinotecan Combination
  • Phase III study
  • Stomach Neoplasms