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

Stomach Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00525005
• Other study ID #: HMC-HO-GI-0701
• Status: Completed
• Phase: Phase 2
• First received: September 4, 2007
• Last updated: September 20, 2012
• Start date: August 2007
• Est. completion date: June 2010

Study information

• Verified date: September 2012
• Source: Hallym University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stomach Neoplasms

Intervention

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)

Locations

Country	Name	City	State
Korea, Republic of	Hallym University Medical Center	Anyang
Korea, Republic of	Asan Medical Center	Seoul

Sponsors (3)

Lead Sponsor	Collaborator
Hallym University Medical Center	Asan Medical Center, Sanofi

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (6)

Richards D, Wilfong L, Sborov M, McCollum D, Khan M, Boehm K, Zhan F. Phase II trial of docetaxel+oxaliplatin in advanced gastroesophageal and/or stomach cancer. 7th World Congr Gastrointest cancer. 2005: Abs: P-143

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

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. — View Citation

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. — View Citation

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

Zang D, Yang D, Lee H, Lee B, Hwang S, Kim H, Song H, Jung J, Kim J, Kwon J. Phase I study of docetaxel, oxalipaltin and S-1 (DOS) for patients with advanced gastric cancer. Ann Oncol 2007 Sep 23; Abs:in press

Outcome

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