Docetaxel, Oxaliplatin and S-1 (DOS) for Advanced Gastric Cancer

Sponsor

Hallym University Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00525005

Collaborator

Asan Medical Center (Other), Sanofi (Industry)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stomach Neoplasms	Drug: DOS (Docetaxel, Oxaliplatin and S-1)	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2007

Actual Primary Completion Date :

Jun 1, 2010

Actual Study Completion Date :

Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DOS (Docetaxel, Oxaliplatin and S-1) 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)	Drug: DOS (Docetaxel, Oxaliplatin and S-1) 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) Other Names: Taxotere Eloxatin TS-1

Arm

Intervention/Treatment

Experimental: DOS (Docetaxel, Oxaliplatin and S-1)

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)

Drug: DOS (Docetaxel, Oxaliplatin and S-1)

Other Names:

Taxotere

Eloxatin

TS-1

Outcome Measures

Primary Outcome Measures

overall response rate [2.5 years]

Secondary Outcome Measures

safety, progression-free survival, and overall survival [2.5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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