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
  Purpose

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.


Condition Intervention
Breast Cancer
Menopausal Symptoms
Drug: tamoxifen citrate
Genetic: gene expression analysis
Other: pharmacogenomic studies
Other: questionnaire administration
Procedure: quality-of-life assessment

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 501
Study Start Date: June 2008
Estimated Study Completion Date: August 2015
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Tamoxifen 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.

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 (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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00764322

Locations
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
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Lisa A. Carey, MD UNC Lineberger Comprehensive Cancer Center
Principal Investigator: William J. Irvin, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00764322     History of Changes
Other Study ID Numbers: LCCC 0801, P30CA016086, 08-0483
Study First Received: October 1, 2008
Last Updated: November 1, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
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

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Tamoxifen
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 19, 2014