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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00815555
• Other study ID #: 135/08
• Status: Recruiting
• Phase: N/A
• First received: December 28, 2008
• Last updated: December 29, 2008
• Start date: December 2008

Study information

• Verified date: December 2008
• Source: Assaf-Harofeh Medical Center
• Contact: Matitiahu Berkovitch, Prof
• Phone: 972-57-345152
• Email: mberkovitch[@]asaf.health.gov.il
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Female

• Age > 18

• Treated with Tamoxifen following diagnosis of breast cancer

Exclusion Criteria:

Study Design

Time Perspective: Retrospective

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Other:
• There is no intervention - this is an observational study

Locations

Country	Name	City	State
Israel	Clinical Pharmacology Unit - Assaf Harofeh Medical Center	Zerifin

Sponsors (1)

Lead Sponsor	Collaborator
Assaf-Harofeh Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tamoxifen efficacy for avoiding breast cancer relapse in relation to CYP2D6 genotype
Secondary	Prevalence of CYP2D6 poor metabolizers genotype in Israeli female population treated with Tamoxifen