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Validating CYP2D6 Genotype-Guided Tamoxifen Therapy for a Multiracial U.S. Population

21 Years
Open (Enrolling)
Breast Cancer, Menopausal Symptoms

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Trial Information

Validating CYP2D6 Genotype-Guided Tamoxifen Therapy for a Multiracial U.S. Population



- 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.

Inclusion Criteria


- 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


- 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

- No history of allergic reaction to tamoxifen citrate or any of its reagents


- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome 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

Outcome Time Frame:

2-3 years

Safety Issue:


Principal Investigator

Lisa A. Carey, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:

LCCC 0801



Start Date:

June 2008

Completion Date:

August 2015

Related Keywords:

  • Breast Cancer
  • Menopausal Symptoms
  • 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
  • Breast Neoplasms
  • Carcinoma in Situ
  • Carcinoma, Intraductal, Noninfiltrating



Duke Comprehensive Cancer Center Durham, North Carolina  27710
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill, North Carolina  27599-7570
Blumenthal Cancer Center at Carolinas Medical Center Charlotte, North Carolina  28232-2861
Moses Cone Regional Cancer Center at Wesley Long Community Hospital Greensboro, North Carolina  27401
Leo W. Jenkins Cancer Center at ECU Medical School Greenville, North Carolina  27834
Rex Cancer Center at Rex Hospital Raleigh, North Carolina  27607
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center Spartanburg, South Carolina  29303