Breath Test for Women Receiving Tamoxifen in the Prevention or Treatment of Breast Cancer
This study has been terminated.
(Funding issues)
Sponsor:
Mayo Clinic
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00873366
First received: March 31, 2009
Last updated: December 28, 2011
Last verified: December 2011
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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:
Genetics Home Reference related topics:
breast cancer
Drug Information available for:
Dextromethorphan hydrobromide
Dextromethorphan
Tamoxifen
Tamoxifen citrate
U.S. FDA Resources
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: | June 2012 (Final data collection date for primary outcome measure) |
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
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
Additional Information:
No publications provided
| Responsible Party: | Matthew P. Goetz, M.D., Mayo Clinic Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00873366 History of Changes |
| Other Study ID Numbers: | CDR0000637266, P30CA015083, MC083C, 08-007073 |
| Study First Received: | March 31, 2009 |
| Last Updated: | December 28, 2011 |
| 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 Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs |
Antitussive Agents Central Nervous System Agents Therapeutic Uses Respiratory System Agents Antineoplastic Agents, Hormonal Antineoplastic Agents Selective Estrogen Receptor Modulators Estrogen Receptor Modulators Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Bone Density Conservation Agents Estrogen Antagonists |
ClinicalTrials.gov processed this record on May 16, 2013