A Phase I/II Trial of Docetaxel and Oxaliplatin in Patients With Advanced Gastric Cancer (DO for AGC)
Gastric cancer is the most common malignancy in Korea. The prognosis of unresectable gastric cancer has been improved by cytotoxic chemotherapy, but median survival rarely exceeds 1 year. New agents such as taxane, irinotecan and oxaliplatin combined with old agents such as 5-FU with or without leucovorin, doxorubicin, cisplatin showed higher response rates in phase II studies. Docetaxel as a single agents showed response rates of 17-24%, and the combination of docetaxel and cisplatin has shown a response rate of 37-56% and overall survival of 9-10.4 months. Oxaliplatin in combination with 5-FU and leucovorin(FOLFOX-6) showed an objective response rate of 50%, which included a 4% complete response. The preclinical studies, oxaliplatin has shown additive or synergistic cytotoxic properties with fluoropyrimidines, thymidylate synthase inhibitors, topoisomerase I inhibitors, microtubule inhibitors and DNA modifying/alkylating agents. The combination of docetaxel and oxaliplatin has been studied previously in the phase I setting in patients with metastatic breast and non-small cell lung cancer. The combination of docetaxel and oxaliplatin is a feasible and well tolerated regimen. Recommended doses were 75mg/m2 for docetaxel on day 1 and 70mg/m2 for oxaliplatin on day 2 without G-CSF support. The aim of this trial is to determine the dose limiting toxicities, maximum tolerated dose(MTD) and efficacy of oxaliplatin and docetaxel as combination chemotherapy in patients with advanced gastric cancer.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Trial of Docetaxel and Oxaliplatin in Patients With Advanced Gastric Cancer|
- To define the dose-limiting toxicity and maximum tolerated dose in phase I study To evaluate the overall response rate in phase II study [ Time Frame: Two years ] [ Designated as safety issue: Yes ]
- 1) To evaluate the safety and tolerability of the treatment combination. 2) To estimate overall survival. 3) To estimate the time to progression and the duration of overall response. [ Time Frame: Two years ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2006|
|Study Completion Date:||June 2008|
|Primary Completion Date:||March 2008 (Final data collection date for primary outcome measure)|
Drug: docetaxel, oxaliplatin
Oxaliplatin will be administered in combination with docetaxel as a first-line chemotherapy in advanced gastric cancer patients. Each cycle is repeated every 3 weeks.
Docetaxel Oxaliplatin Level 1 60 mg/m2/day 1 100 mg/m2/day 1 Level 2 75 mg/m2/day 1 100 mg/m2/day 1 Level 3 75 mg/m2/day 1 130 mg/m2/day 1
Primary objectives :
To define the dose-limiting toxicity and maximum tolerated dose in phase I study To evaluate the overall response rate in phase II study
Secondary objectives :
- To evaluate the safety and tolerability of the treatment combination.
- To estimate overall survival.
- To estimate the time to progression and the duration of overall response.
|Korea, Republic of|
|Samsung Medical Center|
|Seoul, Korea, Republic of, 135-710|
|Principal Investigator:||Young Suk Park, M.D., Ph.D.||Samsung Medical Center, Seoul, KOREA|