Trial Overview

Status	Condition	Sponsor/Collaborator(s)	First Received	Last Changed	Verification Date
Completed	Stomach Neoplasms	Hallym University Medical Center Other collaborator(s): Asan Medical Center; Sanofi-Aventis	September 4, 2007	September 20, 2012	September 2012

Study Type	Study Design	Phase	Enrollment	Start Date	End Date
Interventional	Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment	Phase 2	44	August 2007	-

Locations

Facility	Address	Contact	Phone	Email	Status
Hallym University Medical Center	Anyang 431-070 Korea, Republic of	-	-	-	-
Asan Medical Center	Seoul 138-736 Korea, Republic of	-	-	-	-

Intervention

Type	Intervention	Description
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)

Outcome

Type	Measure	Time Frame	Safety Issue
Primary	overall response rate	2.5 years	No
Secondary	safety, progression-free survival, and overall survival	2.5 years	Yes

Official Title

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

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.

Eligibility

Gender	Minimum Age	Maximum Age	Healthy Volunteers
Both	-	70 Years	No

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

Citations

PMID 16773074: Yamaguchi K, Shimamura T, Hyodo I, Koizumi W, Doi T, Narahara H, Komatsu Y, Kato T, Saitoh S, Akiya T, Munakata M, Miyata Y, Maeda Y, Takiuchi H, Nakano S, Esaki T, Kinjo F, Sakata Y. Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer. Br J Cancer. 2006 Jun 19;94(12):1803-8.

PMID 16740764: Yoshida K, Ninomiya M, Takakura N, Hirabayashi N, Takiyama W, Sato Y, Todo S, Terashima M, Gotoh M, Sakamoto J, Nishiyama M. Phase II study of docetaxel and S-1 combination therapy for advanced or recurrent gastric cancer. Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3402-7.

Zang D, Song H, Kwon J, Jung J, Kim H, Kim J, Shin H, Park Y. Phase I/II trial with docetaxel and S-1 for patients with advanced or recurrent gastric cancer. Ann Oncol. 2006 Sep 29;17(S9):ix314, Abs:1097P

Schinzari G, D'Argento E, Quirino M, Basso M, Trigila N, Di Leonardo G, Cassano A, Pozzo C, Barone C. Docetaxel and oxaliplatin combination as second-line treatment in patients with advanced gastric cancer. J Clin Oncol. 2005 Jun 1;23(16S Pt1 Suppl):354s, Abs:4188