Breath Test for Women Receiving Tamoxifen in the Prevention or Treatment of Breast Cancer

NCT ID: NCT00873366

Last Updated: 2018-01-23

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 92 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2015-09-23

Brief Summary

RATIONALE: A breath test that measures enzymes may be effective in identifying women in whom tamoxifen may not be effective.

PURPOSE: This clinical trial is studying a breath test to see how well it works in women receiving tamoxifen for the prevention or treatment of breast cancer.

Detailed Description

OBJECTIVES:

• To assess the operating characteristics of the ¹³C-dextromethorphan (^13 C-DM) breath test in identifying women with breast cancer (or at high risk) who are CYP2D6-genotypic poor metabolizers.
• To examine the correlation between CYP2D6 enzyme activity (as measured by the breath test) and plasma endoxifen (and 4-hydroxyTAM) levels in patients who carry one or more CYP2D6 functional alleles.
• To examine the change in CYP2D6 enzyme activity (as measured by the ¹³C-DM breath test), in patients who start a CYP2D6 inhibitor while taking tamoxifen.
• To determine whether CYP2D6 enzyme activity (as measured by the breath test) changes over time (either as a consequence of drug-induced inhibition or other).
• To measure genetic variation in additional genes that are later identified to affect the metabolism, uptake, or distribution of tamoxifen (e.g., SULT1A1, UGT).

OUTLINE: Patients receive tamoxifen citrate for 6 months. ^13C-dextromethorphan breath tests are conducted at baseline and periodically during the 6 months.

13C-dextromethorphan breath test: Patients receive oral Alka-Seltzer® Gold (ASG; citric acid, potassium bicarbonate, and sodium bicarbonate) in water, then, 15 minutes later, another ASG dose and oral ¹³C-dextromethorphan. Patients breathe into a bag 1-2 times, and the is bag sealed. ¹³CO_2 levels in the bags are measured.

Blood samples are collected at baseline and periodically for pharmacogenetic and pharmacokinetic studies by reverse phase HPLC with fluorescence detection.

After completion of study therapy, patients are followed annually for 5 years.

Conditions

Breast Cancer

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Interventions

dextromethorphan hydrobromide

Intervention Type: DRUG

tamoxifen citrate

Intervention Type: DRUG

high performance liquid chromatography

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

pharmacogenomic studies

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

fluorescence imaging

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• CYP2D6 genotype known

• Patients determined to be CYP2D6 poor metabolizers (by determination of a genotype test by their Mayo physician prior to study registration) are eligible to proceed with the initial breath test only
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• ECOG performance status 0-2
• Life expectancy > 6 months
• No known impaired hepatic activity defined as ≥ grade 3 AST, alkaline phosphatase, or total bilirubin
• No pulmonary disease (e.g., asthma or other respiratory disease) associated with hypercapnia
• No uncontrolled metabolic disease (e.g., diabetes in the presence of gastroparesis, uncontrolled congestive heart failure, or uncontrolled gastrointestinal disorders [e.g., GERD])
• No prior adverse reaction to dextromethorphan
• No history of chronic liver disease (e.g., hepatitis B or hepatitis C, alcoholic liver disease, cirrhosis, or fibrotic disease)
• Able and willing to fast overnight prior to the study session
• Willing to return to Mayo Clinic for follow-up
• Willing to provide biologic specimens

PRIOR CONCURRENT THERAPY:

• More than 24 hours since prior medications known to slow gastric emptying or gastrointestinal motility (e.g., alcohol, opioid analgesics, anticholinergics [e.g., antihistamines], and loperamide)
• More than 4 weeks since prior and no concurrent CYP2D6 inhibitors or concurrent serotonin-reuptake inhibitors known to be potent CYP2D6 inhibitors (e.g.,paroxetine [Paxil®] and fluoxetine [Prozac®]

• If mild to moderate inhibitors of CYP2D6 are medically necessary, patients may go back on after the 8-week time point
• More than 4 weeks since prior and no concurrent monoamine-oxidase inhibitors (e.g., furazolidone, phenelzine, procarbazine, selegiline, and tranylcypromine)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew P. Goetz, M.D.

Role: STUDY_CHAIR

Mayo Clinic

Donald W. Northfelt, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC083C

Identifier Type: OTHER

Identifier Source: secondary_id

08-007073

Identifier Type: OTHER

Identifier Source: secondary_id

MC083C

Identifier Type: -

Identifier Source: org_study_id