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Trial record 45 of 2158 for:    doxorubicin

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

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ClinicalTrials.gov Identifier: NCT02078388
Recruitment Status : Unknown
Verified March 2014 by Haematology-Oncology, National University Hospital, Singapore.
Recruitment status was:  Recruiting
First Posted : March 5, 2014
Last Update Posted : March 5, 2014
Sponsor:
Information provided by (Responsible Party):
Haematology-Oncology, National University Hospital, Singapore

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


Condition or disease Intervention/treatment
Breast Cancer Drug: Doxorubicin

Detailed Description:
Doxorubicin is one of the cornerstone therapies in adjuvant chemotherapy in early stage breast cancer. Cumulative doses of 240mg/m2 (4 cycles of doxorubicin/cyclophosphamide) and 300mg/m2 (6 cycles of doxorubicin/cyclophosphamide) are typically administered in the adjuvant setting, which is associated with <1% chance of severe cardiotoxicity, and are thus considered 'safe dose ranges'. However, Blanco et al recently reported childhood cancer survivors with the CBR3 (a metabolizing enzyme of doxorubicin) V244M homozygous G genotypes to be at increased risk of cardiomyopathy following exposure to anthracyclines doses as low as 101-150mg/m2, suggesting that there is no safe dose threshold for individuals with certain genotypes. We have previously studied several genes in the doxorubicin pharmacology pathway, including CBR1, CBR3, and AKR1C3, and found correlation between functional variants in CBR3 and AKR1C3 with doxorubicin-induced myelosuppression. The CBR3 G allele is present in about 50-60% of the Singapore population, and we postulate that these common variants may similarly modify the risk of anthracyclines-induced cardiomyopathy in adult breast cancer patients. Post-treatment echocardiography is not routinely performed in patients who complete adjuvant anthracyclines-containing chemotherapy. We believe that some of these high-risk individuals may have subclinical reduced left ventricular ejection fraction that may in the future increase the risk of congestive cardiac failure in the presence of other risk factors (eg hypertension, anemia, serious infection, etc). Identifying these individuals could therefore be important as early treatment with ACE inhibitors may improve cardiac function. Confirming the correlation between genetic variants including the CBR3 V244M can also help to develop a predictive algorithm in the future to identify patients in whom anthracyclines should be avoided.

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Study Type : Observational
Estimated Enrollment : 500 participants
Observational Model: Case-Only
Time Perspective: Prospective
Study Start Date : November 2013
Estimated Primary Completion Date : October 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Group/Cohort Intervention/treatment
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



Primary Outcome Measures :
  1. Change the functional variants in genes involved in doxorubicin pharmacology with doxorubicin-induced cardiomyopathy in adult breast cancer survivors. [ Time Frame: 1 year ]
    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.


Biospecimen Retention:   Samples With DNA
Whole blood


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Pregnancy
  • Breast feeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02078388


Contacts
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Contact: Soo Chin Lee, MBBS 6779 5555 soo_chin_lee@nuhs.edu.sg

Locations
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Singapore
National University Hospital Recruiting
Singapore, Singapore, 119074
Contact: Soo Chin Lee, MBBS    (65) 6779 5555    soo_chin_lee@nuhs.edu.sg   
Principal Investigator: Soo Chin Lee, MBBS         
Sponsors and Collaborators
National University Hospital, Singapore
Investigators
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Principal Investigator: Soo Chin Lee, MBBS National University Hospital, Singapore

Publications:
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Responsible Party: Haematology-Oncology, Lee Soo Chin, National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT02078388     History of Changes
Other Study ID Numbers: 2013/01090
First Posted: March 5, 2014    Key Record Dates
Last Update Posted: March 5, 2014
Last Verified: March 2014
Additional relevant MeSH terms:
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Doxorubicin
Liposomal doxorubicin
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action