Verification of a Pharmacogenetic Approach to Customizing Chemotherapy to Asians

December 10, 2013 updated by: National University Hospital, Singapore

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

Study Overview

Status

Unknown

Conditions

Colorectal Cancer

Study Type

Observational

Enrollment (Anticipated)

750

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Singapore
- - Singapore, Singapore
    - Recruiting
    - Nationa University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Genders Eligible for Study

All

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.

Description

Inclusion Criteria:

Patients with colorectal cancer

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University Hospital, Singapore

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2011

Primary Completion (ANTICIPATED)

August 1, 2014

Study Registration Dates

First Submitted

April 2, 2012

First Submitted That Met QC Criteria

May 10, 2012

First Posted (ESTIMATE)

May 11, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

December 11, 2013

Last Update Submitted That Met QC Criteria

December 10, 2013

Last Verified

December 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

2011/01711

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