Xeloxiri as First-line Treatment in Patients With Advanced Unresectable Pancreatic Adenocarcinoma

This study is currently recruiting participants.
Verified May 2012 by The University of Hong Kong
Sponsor:
Information provided by (Responsible Party):
Dr. YAU Chung Cheung Thomas, The University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01558869
First received: March 18, 2012
Last updated: May 9, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Pancreatic Adenocarcinoma
Drug: Capecitabine
Drug: Oxaliplatin
Drug: Irinotecan
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by The University of Hong Kong:

Primary Outcome Measures:
  • Change in extent of disease [ Time Frame: Change from baseline in size approximately every 4 cycles ] [ Designated as safety issue: No ]
    Objective response rate


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 29
Study Start Date: April 2012
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: Capecitabine
1200 mg/m2 BD orally for 1 week of a 2-week cycle (i.e. 1 week on, 1 week off)
Other Name: Xeloda
Drug: Oxaliplatin
70 mg/m2 IV on day 1 of a 2-week cycle
Other Name: Eloxatin
Drug: Irinotecan
130 mg/m2 IV on day 1 of a 2-week cycle
Other Name: Campto

Detailed Description:

Pancreatic cancer carries extremely dismal overall prognosis that its motality was almost the same as its incidence in 2008.[1] Pancreatic adenocarcinoma is the commonest type of pancreatic cancer and was the fourth leading cause of cancer death in the United States in 2010.[2] 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%.[3]

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.[4] 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.[5] 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.[6]

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.[6] 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.[5]

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults ≥ 18 and < 75 years of age, male or female.
  • Histopathologically or cytologically confirmed adenocarcinoma of the pancreas.
  • ECOG performance status 0 to 2.
  • Adequate bone marrow reserve.
  • Absolute neutrophil count > 1x10^9/L.
  • Total bilirubin <3 times the upper limit of the normal range.
  • Life expectancy ≥ 12 weeks.
  • Signed written informed consent form.

Exclusion Criteria:

  • Prior malignant disease other than pancreatic cancer.
  • Patients suitable for surgical or locoregional therapies.
  • Patients who have prior anticancer therapy for pancreatic cancer.
  • Patients unable to swallow oral medications.
  • Any evidence of brain metastasis (unless the patient is >6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry).
  • Active clinically serious infections (> grade 2 NCI / CTC Adverse Event version 3.0).
  • History of allergy to platinum compounds.
  • Patients who have chronic inflammatory bowel disease and/or bowel obstruction.
  • Patients who have severe bone marrow failure.
  • Patients undergoing renal dialysis.
  • History of HIV infection.
  • Seizure disorder requiring medication (such as steroids or anti-epileptics).
  • Women who are pregnant or breast-feeding, or women of child-bearing potential who are unable or unwilling to practice a highly effective means of contraception.
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of study results.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01558869

Contacts
Contact: Thomas Yau, MBBS (852) 2255 3111 the@netvigator.com

Locations
Hong Kong
Queen Mary Hospital, The University of Hong Kong Recruiting
Hong Kong, Hong Kong
Contact: Thomas Yau       the@netvigator.com   
Principal Investigator: Thomas Yau, MBBS         
Sub-Investigator: Roland Leung, MB ChB         
Sub-Investigator: Hilda Wong, MBBS         
Sub-Investigator: Joanne Chiu, MBBS         
Sponsors and Collaborators
The University of Hong Kong
Investigators
Principal Investigator: Thomas Yau, MBBS The University of Hong Kong
  More Information

Publications:
Ferlay J, Shin HR, Bray F et al (2010) GLOBOCAN 2008 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer. Available from http://globocan.iarc.fr/ (Retrieved November 21, 2011)

Responsible Party: Dr. YAU Chung Cheung Thomas, Clinical Assistant Professor, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT01558869     History of Changes
Other Study ID Numbers: MONC-HBP24
Study First Received: March 18, 2012
Last Updated: May 9, 2012
Health Authority: Hong Kong: Institutional Review Board of the University of Hong Kong/ Hospital Authority Hong Kong West Cluster
Hong Kong: Department of Health

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Oxaliplatin
Irinotecan
Capecitabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on April 17, 2014