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

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ClinicalTrials.gov Identifier: NCT00873366
Recruitment Status : Terminated (Funding issues)
First Posted : April 1, 2009
Last Update Posted : May 25, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
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.


Condition or disease Intervention/treatment
Breast Cancer Drug: dextromethorphan hydrobromide Drug: tamoxifen citrate Other: high performance liquid chromatography Other: laboratory biomarker analysis Other: pharmacogenomic studies Other: pharmacological study Procedure: fluorescence imaging

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.


Study Design

Study Type : Observational
Actual Enrollment : 92 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: ¹³C - Dextromethorphan (DM) Breath Test for Determination of CYP2D6 Enzyme Activity in Patients Receiving Tamoxifen
Actual Study Start Date : May 2009
Primary Completion Date : September 23, 2015
Study Completion Date : September 23, 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Groups and Cohorts


Outcome Measures

Primary Outcome Measures :
  1. Operating characteristics of the ¹³C-dextromethorphan (13C-DM) breath test in identifying those who are CYP2D6 genotypic poor metabolizers
  2. Correlation of the findings of the ¹³C-DM breath test with the ratio of endoxifen to N-desmethyl-tamoxifen (E/NdTAM) and with steady state plasma measurements of 4-hydroxyTAM
  3. Changes in ¹³C-DM breath test results during the course of the study, specifically for patients that initiate a CYP2D6 inhibitor

Eligibility Criteria

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Female breast cancer
Criteria

DISEASE CHARACTERISTICS:

  • 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

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)
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00873366


Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Study Chair: Matthew P. Goetz, M.D. Mayo Clinic
Principal Investigator: Donald W. Northfelt, M.D. Mayo Clinic
More Information

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00873366     History of Changes
Other Study ID Numbers: MC083C
P30CA015083 ( U.S. NIH Grant/Contract )
MC083C ( Other Identifier: Mayo Clinic Cancer Center )
08-007073 ( Other Identifier: Mayo Clinic IRB )
First Posted: April 1, 2009    Key Record Dates
Last Update Posted: May 25, 2017
Last Verified: May 2017

Keywords provided by Mayo Clinic:
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Dextromethorphan
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Antitussive Agents
Respiratory System Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action