Studying Blood Samples From Women With Breast Cancer or Ductal Carcinoma In Situ Who Are Receiving Tamoxifen

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00764322
First received: October 1, 2008
Last updated: November 1, 2013
Last verified: November 2013

October 1, 2008
November 1, 2013
June 2008
March 2010   (final data collection date for primary 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 [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
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 [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00764322 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: Yes ]
  • Feasibility of obtaining pharmacogenomic information from patients in the clinical setting and using it to guide changes in therapy [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
  • CYP2D6 allele frequencies and endoxifen levels among African-American women taking tamoxifen citrate [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Tolerability of increasing the dose of tamoxifen citrate from 20 to 40 mg per day in patients with IM CYP2D6 genotypes [ Designated as safety issue: Yes ]
  • Feasibility of obtaining pharmacogenomic information from patients in the clinical setting and using it to guide changes in therapy [ Designated as safety issue: No ]
  • CYP2D6 allele frequencies and endoxifen levels among African-American women taking tamoxifen citrate [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Studying Blood Samples From Women With Breast Cancer or Ductal Carcinoma In Situ Who Are Receiving Tamoxifen
Validating CYP2D6 Genotype-Guided Tamoxifen Therapy for a Multiracial U.S. Population

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.

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.

Interventional
Not Provided
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Breast Cancer
  • Menopausal Symptoms
  • 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 months
  • Procedure: 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.
Tamoxifen
Interventions:
  • Drug: tamoxifen citrate
  • Genetic: gene expression analysis
  • Other: pharmacogenomic studies
  • Other: questionnaire administration
  • Procedure: quality-of-life assessment
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
501
August 2015
March 2010   (final data collection date for primary outcome measure)

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
Female
21 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00764322
LCCC 0801, P30CA016086, 08-0483
Yes
UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Lisa A. Carey, MD UNC Lineberger Comprehensive Cancer Center
Principal Investigator: William J. Irvin, MD UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP