Studying Blood Samples From Women With Breast Cancer or Ductal Carcinoma In Situ Who Are Receiving Tamoxifen
RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help doctors learn more about differences in DNA and predict how well patients will respond to treatment and plan better treatment.
PURPOSE: This clinical trial is studying blood samples from women with breast cancer or ductal carcinoma in situ who are receiving tamoxifen.
Drug: tamoxifen citrate
Genetic: gene expression analysis
Other: pharmacogenomic studies
Other: questionnaire administration
Procedure: quality-of-life assessment
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Validating CYP2D6 Genotype-Guided Tamoxifen Therapy for a Multiracial U.S. Population|
- Change in endoxifen levels after an increase in the tamoxifen citrate dose from 20 mg to 40 mg in patients with intermediate-metabolizing (IM) CYP2D6 genotypes [ Time Frame: 2-3 years ]
- Tolerability of increasing the dose of tamoxifen citrate from 20 to 40 mg per day in patients with IM CYP2D6 genotypes [ Time Frame: 2-3 years ]
- Feasibility of obtaining pharmacogenomic information from patients in the clinical setting and using it to guide changes in therapy [ Time Frame: 2-3 years ]
- CYP2D6 allele frequencies and endoxifen levels among African-American women taking tamoxifen citrate [ Time Frame: 2-3 years ]
- Change in plasma endoxifen levels after an increase in tamoxifen citrate dose from 20 mg to 40 mg daily in patients with poor-metabolizing genotypes [ Time Frame: 2-3 years ]
|Study Start Date:||June 2008|
|Estimated Study Completion Date:||August 2015|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
Drug: tamoxifen citrate
Women found to be IM or PM will undergo increased tamoxifen to 40 mg/day (20 mg bid). Drug is given orally on a daily basis.Genetic: gene expression analysis
Genetic analysis of blood sample.Other: pharmacogenomic studies
Genetic analysis of blood sample.Other: questionnaire administration
Questionnaire called the survey of participants. Questionnaires is self administered on paper documents and given pre-study, and at 4 monthsProcedure: quality-of-life assessment
Self administration of a multiquestion questionnaire called the FACT-B. Given pre-study, at 4 months and at 8-10 months.
- To evaluate the change in endoxifen levels after an increase in tamoxifen citrate dose from 20 mg to 40 mg in women with breast cancer or ductal breast carcinoma in situ with intermediate-metabolizing CYP2D6 genotypes.
- To evaluate the tolerability of increasing the dose of tamoxifen citrate from 20 to 40 mg per day in these patients.
- To assess the feasibility of obtaining pharmacogenomic information from patients in the clinical setting and using it to guide changes in therapy.
- To examine CYP2D6 allele frequencies and endoxifen levels among African-American women taking tamoxifen citrate.
- To evaluate the change in plasma endoxifen levels after an increase in the tamoxifen citrate dose from 20 mg to 40 mg daily in patients with poor-metabolizing genotypes.
- To study patient understanding of pharmacogenomics and obstacles to participation in clinical trials based upon germline DNA.
OUTLINE: This is a multicenter study.
Blood samples are collected at baseline to determine CYP2D6 genotype and tamoxifen citrate metabolic status (i.e., poor-metabolizing [PM], intermediate-metabolizing [IM], or extensive-metabolizing [EM] alleles). Samples are also analyzed for plasma levels of endoxifen and N-desmethyltamoxifen and for endoxifen/N-desmethyltamoxifen ratio. Patients found to be IM or PM are notified to increased tamoxifen citrate to 40 mg/day for 4 months (in the absence of unacceptable toxicity) with repeat endoxifen and N-desmethyltamoxifen levels (and the ratio) at the end of this time.
All patients complete Quality Of Life (QOL) and Menopausal Symptoms Scale (MSS) questionnaires at baseline and after 4 months of treatment. Toxicities are assessed at the end of 4 months. Patients undergo repeat questionnaire assessment of their understanding of the use of pharmacogenomics in clinical decision-making. Some patients also undergo a 30-minute, baseline interview regarding attitudes and experience towards participation in a pharmacogenomics study.
Patients who choose to be informed of the results of their genotyping are contacted by letter, along with their physicians, and offered genetic counseling to discuss the significance of these results.
After completion of study therapy, patients are followed at 3-6 months, including toxicity assessment and QOL and MSS questionnaires.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00764322
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599-7295|
|Blumenthal Cancer Center at Carolinas Medical Center|
|Charlotte, North Carolina, United States, 28232-2861|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|Moses Cone Regional Cancer Center at Wesley Long Community Hospital|
|Greensboro, North Carolina, United States, 27403-1198|
|Leo W. Jenkins Cancer Center at ECU Medical School|
|Greenville, North Carolina, United States, 27834|
|Rex Cancer Center at Rex Hospital|
|Raleigh, North Carolina, United States, 27607|
|United States, South Carolina|
|Gibbs Regional Cancer Center at Spartanburg Regional Medical Center|
|Spartanburg, South Carolina, United States, 29303|
|Principal Investigator:||Lisa A. Carey, MD||UNC Lineberger Comprehensive Cancer Center|
|Principal Investigator:||William J. Irvin, MD||UNC Lineberger Comprehensive Cancer Center|