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

This study has been terminated.
(Funding issues)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00873366
First received: March 31, 2009
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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 Intervention
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

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Diagnostic
Official Title: ¹³C - Dextromethorphan (DM) Breath Test for Determination of CYP2D6 Enzyme Activity in Patients Receiving Tamoxifen

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Operating characteristics of the ¹³C-dextromethorphan (13C-DM) breath test in identifying those who are CYP2D6 genotypic poor metabolizers [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • Changes in ¹³C-DM breath test results during the course of the study, specifically for patients that initiate a CYP2D6 inhibitor [ Designated as safety issue: No ]

Estimated Enrollment: 210
Study Start Date: May 2009
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Investigators
Study Chair: Matthew P. Goetz, M.D. Mayo Clinic
Principal Investigator: Donald W. Northfelt, M.D. Mayo Clinic in Arizona
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00873366     History of Changes
Other Study ID Numbers: MC083C, P30CA015083, MC083C, 08-007073
Study First Received: March 31, 2009
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

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
Dextromethorphan
Tamoxifen
Antitussive Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Respiratory System Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 28, 2014