Overview

This trial is active, not recruiting.

Conditions breast cancer, menopausal symptoms
Treatments tamoxifen citrate, gene expression analysis, pharmacogenomic studies, questionnaire administration, quality-of-life assessment
Sponsor UNC Lineberger Comprehensive Cancer Center
Collaborator National Cancer Institute (NCI)
Start date June 2008
End date March 2010
Trial size 501 participants
Trial identifier NCT00764322, 08-0483, LCCC 0801, P30CA016086

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Other)
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.
gene expression analysis
Genetic analysis of blood sample.
pharmacogenomic studies
Genetic analysis of blood sample.
questionnaire administration
Questionnaire called the survey of participants. Questionnaires is self administered on paper documents and given pre-study, and at 4 months
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.

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
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

Eligibility Criteria

Female participants at least 21 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed invasive carcinoma of the breast or ductal breast carcinoma in situ - Has been receiving tamoxifen citrate at a dose of 20 mg/day for at least 4 months either for the treatment of invasive or non-invasive carcinoma of the breast or for breast cancer recurrence prevention - Expected duration of tamoxifen citrate treatment at least 6 months - Hormone receptor status not specified PATIENT CHARACTERISTICS: - Menopausal status not specified - ECOG performance status 0-2 - Life expectancy ≥ 6 months - ANC ≥ 1.0 x 10^9/L - Platelet count ≥ 100 x 10^9/L - AST and ALT ≤ 2.5 times upper limit of normal (ULN) - Total bilirubin ≤ 2.5 times ULN - Creatinine clearance ≥ 50 mL/min - Not pregnant or nursing - Fertile patients must use effective contraception - No active, serious infection or medical or psychiatric illness likely to preclude study participation - No psychiatric conditions that would preclude study compliance or informed consent - No history of venous thromboembolism, transient ischemic attack, or cerebral vascular accident - No history of allergic reaction to tamoxifen citrate or any of its reagents PRIOR CONCURRENT THERAPY: - No limitations to number of prior therapies - No limitations for prior radiotherapy - More than 14 days since prior and no other concurrent investigational agent - No concurrent coumadin - No concurrent medications known to inhibit CYP2D6, including any of the following: - Amiodarone - Haloperidol - Indinavir - Ritonavir - Quinidine - No concurrent selective serotonin reuptake inhibitors, except the following: - Venlafaxine - Citalopram - Concurrent participation in non-treatment studies allowed provided it will not interfere with participation in this study

Additional Information

Official title Validating CYP2D6 Genotype-Guided Tamoxifen Therapy for a Multiracial U.S. Population
Principal investigator Lisa A. Carey, MD
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 (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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2013.
Information provided to ClinicalTrials.gov by UNC Lineberger Comprehensive Cancer Center.