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¹³C - Dextromethorphan (DM) Breath Test for Determination of CYP2D6 Enzyme Activity in Patients Receiving Tamoxifen

18 Years
Not Enrolling
Breast Cancer

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Trial Information

¹³C - Dextromethorphan (DM) Breath Test for Determination of CYP2D6 Enzyme Activity in Patients Receiving Tamoxifen


- 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.

Inclusion Criteria


- Eligible to receive tamoxifen for 6 months for either the prevention or treatment of
non-invasive or invasive, stage I-III breast cancer

- 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


- 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

- 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


- 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)

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Diagnostic

Outcome Measure:

Operating characteristics of the ¹³C-dextromethorphan (13C-DM) breath test in identifying those who are CYP2D6 genotypic poor metabolizers

Safety Issue:


Principal Investigator

Matthew P. Goetz, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

May 2009

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage I breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • Breast Neoplasms



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Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404