Xeloxiri as First-line Treatment in Patients With Advanced Unresectable Pancreatic Adenocarcinoma
This is an open-label, single centre, single-arm phase II study which aims to assess the efficacy and tolerability of triplet combination of capecitabine, oxaliplatin and irinotecan (Xeloxiri regimen) in treating patients with advanced unresectable pancreatic carcinoma. Clinical data from patients diagnosed with pancreatic adenocarcinoma will be collected and analyzed in this study. The patients' data will be collected and maintained in the Division of Medical Oncology of the University Department of Medicine, Queen Mary Hospital, Hong Kong.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label, Single-centre, Single-arm Phase II Study of Capecitabine Combined With Oxaliplatin and Irinotecan (Xeloxiri) as First-line Treatment in Patients With Advanced Unresectable Pancreatic Adenocarcinoma|
- Change in extent of disease [ Time Frame: Change from baseline in size approximately every 4 cycles ] [ Designated as safety issue: No ]Objective response rate
- CA19.9 reduction [ Time Frame: Change from baseline every 2 cycles ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: From date of start until the date of first documented progression or death from disease-related causes or last follow-up, whichever came first, assessed up to 18 months ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: From date of start until the date of death from any cause or last follow-up, whichever came first, assessed up to 18 months ] [ Designated as safety issue: No ]
|Study Start Date:||April 2012|
|Estimated Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
|Experimental: Arm 1||
1200 mg/m2 BD orally for 1 week of a 2-week cycle (i.e. 1 week on, 1 week off)
Other Name: XelodaDrug: Oxaliplatin
70 mg/m2 IV on day 1 of a 2-week cycle
Other Name: EloxatinDrug: Irinotecan
130 mg/m2 IV on day 1 of a 2-week cycle
Other Name: Campto
Pancreatic cancer carries extremely dismal overall prognosis that its motality was almost the same as its incidence in 2008. Pancreatic adenocarcinoma is the commonest type of pancreatic cancer and was the fourth leading cause of cancer death in the United States in 2010. For all stages combined, the 1- and 5-year relative survival rates are 26% and 6%, respectively. Even for those people diagnosed with local disease, the 5-year survival is only 23%.
Gemcitabine (Gemzar®; Eli Lilly) has become the reference regimen for advanced pancreatic cancer after a randomized trial showed significant improvement in overall survival as compared with fluorouracil (5-FU) administered as an intravenous bolus. Capecitabine (Xeloda®; Roche) is an oral fluoropyrimidine carbamate prodrug designed to generate 5-FU preferentially in tumor cells due to high concentration level of thymidine phosphorylase enzyme. This allows to mimic continuous 5-FU infusion at the tumor site and to reduce exposure of adjacent healthy tissues without causing discomfort and complications related to intravenous (IV) administration. It has been widely used for the treatment of colorectal cancers and breast cancer.
Irinotecan (Campto®; Pfizer) has some clinical activity against advanced pancreatic cancer. Preclinical studies have indicated that irinotecan has synergistic activity when it is administered before 5-FU and leucovorin. Oxaliplatin (Eloxatin®; sanofi-aventis) has clinical activity against pancreatic cancer only when combined with 5-FU. Oxaliplatin and irinotecan show synergistic activity in vitro.
A recent randomized controlled trial demonstrated that a combination of 5-FU, leucovorin, irinotecan and oxaliplatin (Folfirinox regimen) was associated with a survival advantage and had increased toxicity as compared to single-agent gemcitabine in pancreatic cancer patients. Another recent phase I trial showed promising results of the combination of capecitabine, oxaliplatin and irinotecan in metastatic colorectal cancer subjects and suggested that this tritherapy may provide valuable therapeutic alternative, especially in patients with gastrointestinal cancer.
Therefore, it is of interest to explore the possibility to replace IV 5-FU and leucovorin in the Folfirinox regimen with capecitabine and to assess the efficacy and tolerability of this modified regimen in treating patients with advanced unresectable pancreatic carcinoma.
|Contact: Thomas Yau, MBBS||(852) 2255 email@example.com|
|Queen Mary Hospital, The University of Hong Kong||Recruiting|
|Hong Kong, Hong Kong|
|Contact: Thomas Yau firstname.lastname@example.org|
|Principal Investigator: Thomas Yau, MBBS|
|Sub-Investigator: Roland Leung, MB ChB|
|Sub-Investigator: Hilda Wong, MBBS|
|Sub-Investigator: Joanne Chiu, MBBS|
|Principal Investigator:||Thomas Yau, MBBS||The University of Hong Kong|