Verification of a Pharmacogenetic Approach to Customizing Chemotherapy to Asians

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National University Hospital, Singapore
Sponsor:
Information provided by (Responsible Party):
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT01596361
First received: April 2, 2012
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

Interethnic variability in chemotherapy response is becoming increasingly evident, making approaches for customizing chemotherapy treatment to different ethnic populations desirable. At the same time, significant genetic variation has also been observed between ethnic groups, including many germline and somatic pharmacogenetic variants involved in chemotherapy pharmacology. Recently, based on meta-analyses of studies on germline pharmacogenetic variant frequencies and clinical trials, the investigators found that chemotherapy outcomes between Asians and Caucasians colorectal cancer (CRC) patients could potentially be inferred from the frequencies of variants between the ethnic groups and their respective biological functions. In this study, the investigators seek to further clarify the validity of using pharmacogenetic variants to customize chemotherapy between ethnicities through the following specific aims: (1) To verify the differences observed in the frequency of germline pharmacogenetic variants related to chemotherapy between Asian and Caucasian CRC patients, (2) To test whether variations in the frequency of somatic pharmacogenetic gene mutations between Asian and Caucasian CRC patients could be used to infer differences in clinical outcomes between the two ethnicities. (3) (4) For Aim 1, DNA samples from approximately 1000 Asian and Caucasian CRC patients each will be analyzed for the frequency of a panel of germline pharmacogenetic variants identified in our meta-analyses using high-throughput methodology. For Aim 2, meta-analyses will be performed on pharmacogenetic studies and clinical trials to establish the relative frequencies of somatic variants and clinical outcomes in Asian and Caucasian CRC patients. These frequencies will be verified on the same series of DNA samples used in Aim 1. The clinical outcomes inferred from the frequency differences and biological functions will then be compared to those summarized from clinical trials. This data could provide a basis for developing a rational approach to customizing chemotherapy in non-Caucasian populations and improve assessment of drug feasibility in different ethnic populations.If validated, this working hypothesis would be of high clinical interest, giving the opportunity to use this as a DNA prognosis biomarker in CRC.

Pharmacogenetic frequencies could be a potentially useful approach for predicting likely chemotherapy outcomes in non-Caucasian populations


Condition
Colorectal Cancer

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Primary Outcome Measures:
  • Verify the differences observed in the frequency of germline pharmacogenetic variants related to chemotherapy between Asian and Caucasian CRC patients

Secondary Outcome Measures:
  • Testing the variations in the frequency of somatic pharmacogenetic gene mutations between Asian and Caucasian CRC patients could be used to infer differences in clinical outcomes between the two ethnicities.
  • Characterise the deletion status of heat shock protein molecules and determine the association between heat shock protein deletion status and clinico-pathological outcomes in Asian and Caucasian patients with CRC

Estimated Enrollment: 750
Study Start Date: August 2011
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Samples will be obtained from the Tissue Repository, National University Hospital, St. John of God Hospital, Perth, Australia and Kanazawa University, Japan.

Criteria

Inclusion Criteria:

  • Patients with colorectal cancer
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01596361

Contacts
Contact: Ross Soo, MBBS +65 6779 5555 Ross_Soo@nuhs.edu.sg

Locations
Singapore
Nationa University Hospital Recruiting
Singapore, Singapore
Contact: Ross Soo, MBBS    +65 6779 5555    Ross_Soo@nuhs.edu.sg   
Principal Investigator: Ross Soo, MBBS         
Sponsors and Collaborators
National University Hospital, Singapore
  More Information

No publications provided

Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT01596361     History of Changes
Other Study ID Numbers: 2011/01711
Study First Received: April 2, 2012
Last Updated: December 10, 2013
Health Authority: Singapore: Domain Specific Review Boards

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on August 28, 2014