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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00764322
• Other study ID #: LCCC 0801
• Secondary ID: P30CA01608608-04
• Status: Active, not recruiting
• Phase: N/A
• First received: October 1, 2008
• Last updated: November 1, 2013
• Start date: June 2008
• Est. completion date: August 2015

Study information

• Verified date: November 2013
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 501
• Est. completion date: August 2015
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 21 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Carcinoma in Situ
• Menopausal Symptoms

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	North Carolina
United States	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina
United States	Rex Cancer Center at Rex Hospital	Raleigh	North Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		2-3 years	No
Secondary	Tolerability of increasing the dose of tamoxifen citrate from 20 to 40 mg per day in patients with IM CYP2D6 genotypes		2-3 years	Yes
Secondary	Feasibility of obtaining pharmacogenomic information from patients in the clinical setting and using it to guide changes in therapy		2-3 years	No
Secondary	CYP2D6 allele frequencies and endoxifen levels among African-American women taking tamoxifen citrate		2-3 years	No
Secondary	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		2-3 years	No