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

NCT00764322 | Completed Phase 2 Results DMC

• 3 other identifiers: LCCC 0801P30CA01608608-0483
• Study Type: interventional
• Target: 501
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Breast Cancer; Menopausal Symptoms

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Endoxifen Concentrations in Participants Receiving Tamoxifen Citrate Dose of 20 mg or 40 mg Stratified by the Metabolizing CYP2D6 Genotypes

  Measurements of plasma concentrations of the key active metabolite of tamoxifen, endoxifen, were measured at baseline and after 4 months of treatment; The most common CYP2D6 alleles have been grouped by functional activity classifications with descending activity: ultra-rapid (UM), extensive (EM), intermediate (IM) or poor (PM) metabolism. A given patient has two alleles, giving them 10 possible allelic combinations, or diplotypes (UM/UM, UM/EM, EM/EM, etc.). These diplotypes are collapsed into four phenotypes, UM, EM, IM or PM.

  4 months

Secondary Outcomes (5)

• Number of Participants With Pulmonary Embolism (PE), Deep Vein Thrombosis (DVT), Stroke, and/or Endometrial Cancer

  Approximately ten months from registration to last follow-up

• Change in Median Endoxifen Concentrations to Determine Feasibility of Obtaining Pharmacogenomic Information From Patients in the Clinical Setting and Using it to Guide Changes in Therapy

  Baseline and 4 months after dose increase

• CYP2D6 Allele Frequencies and Endoxifen Levels Among African-American Women Taking Tamoxifen Citrate

  baseline

• 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

  Baseline and 4 months after dose increase

• Patient Understanding of Pharmacogenomics

  baseline

Study Arms (2)

Tamoxifen 20

EXPERIMENTAL

One arm, containing the ultra-rapid and extensive metabolizer genotypes, continues treatment with tamoxifen at 20mg.

Drug: tamoxifen citrate; Genetic: gene expression analysis; Other: pharmacogenomic studies; Other: questionnaire administration; Procedure: quality-of-life assessment

Tamoxifen 40

ACTIVE COMPARATOR

This arm, containing the intermediate and poor metabolizer genotypes, receives escalated treatment with tamoxifen at 40mg.

Drug: tamoxifen citrate; Genetic: gene expression analysis; Other: pharmacogenomic studies; Other: questionnaire administration; Procedure: quality-of-life assessment

Interventions

tamoxifen citrate DRUG

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.

Also known as: Nolvadex, Soltamox

Tamoxifen 20; Tamoxifen 40

gene expression analysis GENETIC

Genetic analysis of blood sample.

Tamoxifen 20; Tamoxifen 40

pharmacogenomic studies OTHER

Genetic analysis of blood sample.

Tamoxifen 20; Tamoxifen 40

questionnaire administration OTHER

Questionnaire called the survey of participants. Questionnaires is self administered on paper documents and given pre-study, and at 4 months

Tamoxifen 20; Tamoxifen 40

quality-of-life assessment PROCEDURE

Self administration of a multiquestion questionnaire called the Functional Assessment of Cancer Therapy -Breast (FACT-B). Given pre-study, at 4 months and at 8-10 months.

Tamoxifen 20; Tamoxifen 40

Eligibility Criteria

• Age: 21 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Concurrent participation in non-treatment studies allowed provided it will not interfere with participation in this study Menopausal status not specified Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Life expectancy ≥ 6 months Absolute Neutrophil Count (ANC) ≥ 1.0 x 10\^9/L Platelet count ≥ 100 x 10\^9/L Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times Upper Limit of Normal (ULN) Total bilirubin ≤ 2.5 times ULN Creatinine clearance ≥ 50 mL/min Fertile patients must use effective contraception
• 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

You may not qualify if:

• Not pregnant or nursing 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 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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (7)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, 28232-2861, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Moses Cone Regional Cancer Center at Wesley Long Community Hospital

Greensboro, North Carolina, 27403-1198, United States

Location

Leo W. Jenkins Cancer Center at ECU Medical School

Greenville, North Carolina, 27834, United States

Location

Rex Cancer Center at Rex Hospital

Raleigh, North Carolina, 27607, United States

Location

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Spartanburg, South Carolina, 29303, United States

Location

Related Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Breast Carcinoma In Situ

Interventions

Tamoxifen; Gene Expression Profiling; Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Genetic Techniques; Investigative Techniques; Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Results Point of Contact

• Title: Robin V. Johnson
• Organization: UNC Lineberger Comprehensive Cancer Center

Robin_V_Johnson@med.unc.edu

919-966-1125

Study Officials

• Lisa A. Carey, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• William J. Irvin, MD

  Bon Secours Virginia Health System / Bon Secours Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2008
• First Posted: October 2, 2008
• Study Start: June 18, 2008
• Primary Completion: September 28, 2010
• Study Completion: July 1, 2011
• Last Updated: August 1, 2017
• Results First Posted: July 2, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)