CYP2D6 Genotyping by AmpliChipTM CYP450 for Tamoxifen-Treated Breast Cancer Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2008 by Assaf-Harofeh Medical Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Assaf-Harofeh Medical Center
ClinicalTrials.gov Identifier:
NCT00815555
First received: December 28, 2008
Last updated: December 29, 2008
Last verified: December 2008
  Purpose

The aim of the study is to examine whether tamoxifen-treated Israeli breast cancer patients who are CYP2D6 poor metabolizers (CYP2D6*4/*4 genotype) are at higher cancer relapse risk during 2.5-5-year follow-up period from initial diagnosis and primary treatment.


Condition Intervention
Breast Cancer
Other: There is no intervention - this is an observational study

Study Type: Observational
Study Design: Time Perspective: Retrospective
Official Title: CYP2D6 Genotyping by AmpliChipTM CYP450 for Tamoxifen-Treated Breast Cancer Patients

Resource links provided by NLM:


Further study details as provided by Assaf-Harofeh Medical Center:

Primary Outcome Measures:
  • Tamoxifen efficacy for avoiding breast cancer relapse in relation to CYP2D6 genotype

Secondary Outcome Measures:
  • Prevalence of CYP2D6 poor metabolizers genotype in Israeli female population treated with Tamoxifen

Biospecimen Retention:   Samples With DNA

Blood samples


Estimated Enrollment: 500
Study Start Date: December 2008
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
Women diagnosed with receptor positive breast cancer, treated with Tamoxifen
Other: There is no intervention - this is an observational study

Detailed Description:

Tamoxifen, the first-line drug for preventing breast cancer relapse, is typically prescribed for a 5-year follow-up period after diagnosis and primary treatment of estrogen receptor-positive breast cancer. Recent studies show that tamoxifen is only a pro-drug, while its major active metabolite, endoxifen, is formed in vitro by the liver enzyme CYP2D6. Preliminary observations from the US and Italy have suggested that tamoxifen is less efficacious for cancer relapse prevention in patients with deficient CYP2D6 activities. The FDA is currently reviewing the new data and is likely to modify the tamoxifen label accordingly. It was suggested that an aromatase inhibitor drug such as letrozole might be more beneficial for these patients.

The proposed study would retrospectively test CYP2D6 genotypes in 200 - 300 estrogen receptor (ER) positive breast cancer patients who are treated with tamoxifen post-operatively. Blood collected with informed consent would be used for examining the patients CYP2D6 genotype, and identifying those who are CYP2D6 poor metabolizers (CYP2D6*4/*4 genotype), and for measurement of endoxifen blood level in those women who are on the drug.

AmpliChipTM CYP450 is a microarray chip which contains millions of tiny DNA molecules, providing comprehensive coverage of gene variations that play a role in the metabolism of approximately 25% of all prescription drugs. The AmpliChipTM CYP450 test is intended to be an aid for physicians in individualizing treatment doses for patients receiving therapeutics metabolized through these enzymes.

The clinical data collected would examine if these individuals, as well as those treated with CYP2D6 inhibiting drugs such as paroxetine and fluoxetine, have higher cancer relapse rates.

The study, combined with similar findings from other countries, and possibly integrated later on with an international network study, would be imperative for modifying treatment recommendations for breast cancer therapy. Specifically, if the US and Italian findings are confirmed, it might be advisable to switch the 5-year follow-up treatment for breast cancer patients with ER positive primary tumors who are CYP2D6 poor metabolizers from tamoxifen to an aromatase inhibitor drug such as letrozole.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Women diagnosed with receptor positive breast cancer, treated with Tamoxifen

Criteria

Inclusion Criteria:

  • Female
  • Age > 18
  • Treated with Tamoxifen following diagnosis of breast cancer

Exclusion Criteria:

  • None
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00815555

Contacts
Contact: Matitiahu Berkovitch, Prof 972-57-345152 mberkovitch@asaf.health.gov.il

Locations
Israel
Clinical Pharmacology Unit - Assaf Harofeh Medical Center Recruiting
Zerifin, Israel, 70300
Contact: Matitiahu Berkovitch, Prof    972-57-345152    mberkovitch@asaf.health.gov.il   
Sponsors and Collaborators
Assaf-Harofeh Medical Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00815555     History of Changes
Other Study ID Numbers: 135/08
Study First Received: December 28, 2008
Last Updated: December 29, 2008
Health Authority: Israel: Ministry of Health

Keywords provided by Assaf-Harofeh Medical Center:
receptor positive breast cancer
Tamoxifen treatment
CYP2D6 status
relapse

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents
Estrogen Antagonists

ClinicalTrials.gov processed this record on April 15, 2014