Clinical trial NCT00764322
Conditions: Breast Cancer Menopausal Symptoms
Keywords: menopausal symptoms recurrent breast cancer stage I breast cancer stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer stage IV breast cancer ductal breast carcinoma in situ breast cancer in situ
Sponsor: UNC Lineberger Comprehensive Cancer Center
Start date: 2008-06-18; Completion date: 2011-07-01
Enrollment: 501 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
OBJECTIVES:

Primary

* 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.

Secondary

* 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: 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.

Arms: arm 1: One arm, containing the ultra-rapid and extensive metabolizer genotypes, continues treatment with tamoxifen at 20mg. arm 2: This arm, containing the intermediate and poor metabolizer genotypes, receives escalated treatment with tamoxifen at 40mg.
Interventions: intervention 1: tamoxifen citrate intervention 2: gene expression analysis intervention 3: pharmacogenomic studies intervention 4: questionnaire administration intervention 5: quality-of-life assessment
Intervention descriptions: intervention 1: 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. intervention 2: Genetic analysis of blood sample. intervention 3: Genetic analysis of blood sample. intervention 4: Questionnaire called the survey of participants. Questionnaires is self administered on paper documents and given pre-study, and at 4 months intervention 5: Self administration of a multiquestion questionnaire called the Functional Assessment of Cancer Therapy -Breast (FACT-B). Given pre-study, at 4 months and at 8-10 months.

Protocol documents: