Correlation Between Genetic Variants and Long-term Cardiac Effects Induced by Doxorubicin in Breast Cancer Patients

NCT02078388 | Unknown

• 1 other identifier: 2013/01090
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to identify the genetic variants that are associated with higher risk of doxorubicin-induced cardiotoxicity can contribute towards developing a predictive algorithm comprising both clinical and genetic factors to select patients who should avoid treatment with anthracyclines. Hypothesis of this study is certain functional variants in genes that encode for metabolizing enzymes and/or targets in the doxorubicin pharmacology pathway may increase the risk of doxorubicin-induced cardiomyopathy

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Change the functional variants in genes involved in doxorubicin pharmacology with doxorubicin-induced cardiomyopathy in adult breast cancer survivors.

  Identification of genetic variants that are associated with higher risk of doxorubicin-induced cardiotoxicity can contribute towards developing a predictive algorithm comprising both clinical and genetic factors to select patients who should avoid treatment with anthracyclines.

  1 year

Study Arms (1)

Breast cancer,Doxorubicin

Breast cancer patients who received at least one cycle of doxorubicin-containing adjuvant chemotherapy for treatment of early stage breast cancer at least 12 months ago and who had a pre-doxorubicin echocardiography done at NUHS will be enrolled. Study subjects will donate one sample of blood (20ml) for genetic and biomarker studies related to breast cancer and anthracyclines pharmacodynamics. An echocardiography will be performed to measure left ventricular ejection fraction, and compared with the subject's pre-doxorubicin echocardiography done at NUH. Correlative analysis will be performed between genetic variants and left ventricular ejection change.

Drug: Doxorubicin

Interventions

Doxorubicin DRUG

Breast cancer,Doxorubicin

Eligibility Criteria

• Age: 21 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Breast cancer patients who received at least one cycle of doxorubicin-containing adjuvant chemotherapy for treatment of early stage breast cancer at least 12 months ago and who had a pre-doxorubicin echocardiography done at NUHS will be enrolled.

You may qualify if:

• Age \>= 21 years
• Signed informed consent from patient or legal representative.

You may not qualify if:

• Pregnancy
• Breast feeding.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, 119074, Singapore

RECRUITING

Related Publications (2)

• Blanco JG, Sun CL, Landier W, Chen L, Esparza-Duran D, Leisenring W, Mays A, Friedman DL, Ginsberg JP, Hudson MM, Neglia JP, Oeffinger KC, Ritchey AK, Villaluna D, Relling MV, Bhatia S. Anthracycline-related cardiomyopathy after childhood cancer: role of polymorphisms in carbonyl reductase genes--a report from the Children's Oncology Group. J Clin Oncol. 2012 May 1;30(13):1415-21. doi: 10.1200/JCO.2011.34.8987. Epub 2011 Nov 28.

  PMID: 22124095 BACKGROUND

• Fan L, Goh BC, Wong CI, Sukri N, Lim SE, Tan SH, Guo JY, Lim R, Yap HL, Khoo YM, Iau P, Lee HS, Lee SC. Genotype of human carbonyl reductase CBR3 correlates with doxorubicin disposition and toxicity. Pharmacogenet Genomics. 2008 Jul;18(7):621-31. doi: 10.1097/FPC.0b013e328301a869.

  PMID: 18551042 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Soo Chin Lee, MBBS

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Soo Chin Lee, MBBS

CONTACT

6779 5555; soo_chin_lee@nuhs.edu.sg

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lee Soo Chin

Study Record Dates

• First Submitted: December 8, 2013
• First Posted: March 5, 2014
• Study Start: November 1, 2013
• Primary Completion: October 1, 2015
• Last Updated: March 5, 2014

Record last verified: 2014-03

Locations

SG (1)