Official Title: “A Phase II Study of Docetaxel, Oxaliplatin and S-1 (DOS) in Patients With Advanced Gastric Cancer”

The purpose of this study is to determine the efficacy of combination of docetaxel, oxaliplatin, and S-1 (DOS) in the treatment of advanced gastric cancer.

Study Type: Interventional

Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2009

Docetaxel is an anti-microtubule agent. Docetaxel is an active agent for gastric cancer, with response rate (RR) of 20-24% as a single agent and RR of 37-40% as a combination therapy with 5-FU and/or cisplatin.

S-1 is a new oral dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine (DIF). In two late phase II studies of S-1 for advanced gastric cancer, RR was 45%, with very low (2%) incidence of grade 3 toxicity.

Recent phase I/II trial of the combination of docetaxel and S-1 in patients with advanced gastric cancer suggests that repeated 3-4 week cycles of S-1 60-80mg/m2 /day for 14 days combined with docetaxel 40-75mg/m2 is feasible.

Oxaliplatin, diaminocyclohexane-platinum, is an alkylating agent inhibiting DNA replication.

Comparing to cisplatin or carboplatin, oxaliplatin appear to be more effective and has a more favorable toxicity profile. Phase II studies of the combination of docetaxel and oxaliplatin in patients with advanced gastric cancer suggests that docetaxel 60 or 75mg/m2 combined with oxaliplatin 130 or 80mg/m2 every 3 weeks is feasible.

Recent dose finding study of the combination of docetaxel, oxaliplatin and S-1 (DOS) in patients with advanced gastric cancer suggests that docetaxel 52.5mg/m2 on day 1 and oxaliplatin 105mg/m2 on day 1 combined with S-1 80mg/m2 on day1 to day 14 every 3 weeks is feasible.

Docetaxel, S-1 and oxaliplatin have distinct mechanisms of action and no overlapped key toxicities. Furthermore, fluoropyrimidine and docetaxel or oxaliplatin have shown synergism in vivo studies and in clinical trials. Based on these results, the combination of DOS is a reasonable candidate of new chemotherapeutic regimen for the advanced gastric cancer.

Intervention(s) in this Clinical Trial

• Drug: docetaxel; oxaliplatin; S-1
  • Treatment will be delivered as a 3-week cycle. Docetaxel 52.5mg/m2 IV on D1 (diluted in 250 ml of normal saline over a 1 hour of each cycle before oxaliplatin) Oxaliplatin 105mg/m2 IV on D1 (diluted in 250 ml of 5% DW for 2 hours) S-1 80mg/m2/day on D1-14 (2 weeks of treatment followed by a 1-week rest period) Treatment will be repeated until disease progression, or unacceptable toxicities or patient's refusal.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Docetaxel + oxaliplatin + S-1 (DOS)

Primary Measures

• overall response rate
  • Time Frame: 2.5 years
    Safety Issue?: No

Secondary Measures

• safety, progression-free survival, and overall survival
  • Time Frame: 2.5 years
    Safety Issue?: Yes

Inclusion Criteria:

• Histologically confirmed gastric adenocarcinoma, initially diagnosed or recurred
• Unresectable, locally advanced or metastatic
• At least one uni-dimensional measurable lesion by RECIST criteria
• Age 18 to 70 years old
• ECOG performance status ≤2
• Estimated life expectancy ≥3 months
• Adequate bone marrow function (WBCs ≥4,000/µL or absolute neutrophil count ≥1,500/µL, platelets ≥100,000/µL),
• Adequate kidney function (creatinine <1.5 mg/dL)
• Adequate liver function (bilirubin ≤1.8 mg/dL, transaminase levels <2 times the upper normal limit
• Written informed consent

Exclusion Criteria:

• Other tumor type than adenocarcinoma
• Previous history of chemotherapy (exception: adjuvant chemotherapy)
• Presence of CNS metastasis, psychosis, or seizure
• Obvious bowel obstruction
• Evidence of serious gastrointestinal bleeding
• Peripheral neuropathy (NCI CTC >= Grade I)
• Past or concurrent history of neoplasm other than gastric adenocarcinoma, except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix uteri
• Pregnant or lactating women, women of childbearing potential not employing adequate contraception
• Other serious illness or medical conditions

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Hallym University Medical Center

Overall Clinical Trial Officials and Contacts

Dae Young Zang, MD, PhD Principal Investigator Hallym University Medical Center  

Overall Contact: Dae Young Zang, MD, PhD 82-31-380-3871 fhdzang@kornet.net

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00525005

Study ID Number: HMC-HO-GI-0701

ClinicalTrials.gov Identifier: NCT00525005

Health Authority: Korea: Food and Drug Administration