Breast CancerNCT00283608
Pharmacogenetics of Anastrozole in Postmenopausal Women With Estrogen Receptor-Positive and/or Progesterone Receptor-Positive Stage I, Stage II, or Stage III Breast Cancer
An observational study of Breast Cancer, run by Mayo Clinic at 4 sites in United States.
Trial summary
RATIONALE: Studying samples of blood in the laboratory from patients with cancer receiving anastrozole may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors learn more about how anastrozole works in the body. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Single nucleotide polymorphism (SNP), high performance liquid chromatography and measurements by DXA
- How many people
- 1,000 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2005to Mar 2010
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Diagnosis of breast cancer. Stage I, II, or III disease. Planning to undergo treatment with anastrozole at the clinically approved dose of 1 mg/day OR Mayo Clinic Cancer Center Rochester patient who will be enrolled on or has been enrolled on CAN-NCIC-MA27 and has not started taking the study medication (anastrozole or exemestane)
DISEASE CHARACTERISTICS:
- Diagnosis of breast cancer
- Stage I, II, or III disease
- Resected disease
- Planning to undergo treatment with anastrozole at the clinically approved dose of 1 mg/day OR Mayo Clinic Cancer Center Rochester patient who will be enrolled on or has been enrolled on CAN-NCIC-MA27 and has not started taking the study medication (anastrozole or exemestane)
- Hormone receptor status:
- Estrogen receptor-positive and/or progesterone receptor-positive primary tumor
PATIENT CHARACTERISTICS:
- Female
- Postmenopausal
- Able to complete questionnaires alone or with assistance
PRIOR CONCURRENT THERAPY:
- More than 6 months since prior endocrine therapy, except tamoxifen
- No other prior aromatase inhibitors (e.g., letrozole or exemestane)
- No prior ovarian function suppression with surgery or radiotherapy, ovarian ablation, or luteinizing hormone-releasing hormone analogues (e.g., goserelin) as treatment for cancer
Trial locations and contacts
4 sites in 1 country.
United States4 sites
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
Mayo Clinic in Florida
Jacksonville, Florida, 32224
Mayo Clinic
Rochester, Minnesota, 55905
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259-5499
About this study
Official title: Pharmacogenetics of Aromatase Inhibitors
RATIONALE: Studying samples of blood in the laboratory from patients with cancer receiving anastrozole may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors learn more about how anastrozole works in the body.
PURPOSE: This research study is looking at the pharmacogenetics of anastrozole in postmenopausal women with estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+) stage I, stage II, or stage III breast cancer.
Read the detailed description
OBJECTIVES:
- To evaluate the association of intragenic haplotypes in genes encoding proteins involved in anastrozole metabolism pathways with anastrozole steady state plasma levels in postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive stage I, II, or III breast cancer.
- To evaluate the association of intragenic haplotypes in genes that encode proteins involved in pathways for estrogen synthesis, metabolism, and transport and in genes involved in anastrozole metabolism with the pharmacodynamic (PD) effects of anastrozole therapy, as measured by changes (before vs after drug therapy) in plasma levels of estradiol, estrone, estrone sulfate, testosterone, and androstenedione in these patients.
- To evaluate the association of intragenic haplotypes described above with the PD effects of anastrozole therapy, as measured by changes in breast density and bone mineral density before and at 1 year after drug therapy.
- To collect and bank blood samples and mammographic, bone density, and questionnaire data from patients enrolled on CAN-NCIC-MA27 and randomized to receive exemestane.
OUTLINE: This is a multicenter study. Patients are stratified according to prior tamoxifen use (yes vs no).
Blood samples are obtained for pharmacogenetic studies at baseline, at 6-12 weeks, and then at 1 year. Samples are analyzed for plasma anastrozole concentrations via high-performance liquid chromatography; genotyping for htSNPs via PCR; plasma levels of estradiol, estrone, estrone sulfate, testosterone, and androstenedione via gas chromatographic negative chemical ionization tandem mass spectrometry and liquid chromatographic electrospray tandem mass spectrometry.
Mammograms are obtained at baseline (i.e., within the past 6 months) and at 1 year to assess breast density. Patients with bilateral disease, bilateral breast augmentation, or bilateral mastectomy do not participate in this portion of the study.
Patients at the Mayo Clinic Cancer Center Rochester site also undergo bone mineral density measurement via dual x-ray absorptiometry at baseline and at 1 year. Metabolic markers of bone formation and resorption are also assessed in the Mayo Clinic patients.
Blood samples and mammographic, bone mineral density, and questionnaire data collected from patients randomized to receive exemestane on CAN-NCIC-MA27 are stored for future studies.
Patients complete a questionnaire at baseline, at 6-12 weeks, and at 1 year.
- Conditions
- Breast Cancer
- Being tested
- Single nucleotide polymorphism (SNP), high performance liquid chromatography, measurements by DXA, questionnaire administration
- Keywords
- stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single nucleotide polymorphism (SNP)Genetic
Evaluating SNP association with traits.
high performance liquid chromatographyOther
analysis of plasma concentrations of drugs
measurements by DXAOther
determine bone mineral density (BMD)
questionnaire administrationOther
determine attitude changes
| Study group | Role | What they receive |
|---|---|---|
| Anastrozole | Blood draws for baseline and six to twelve weeks. Receives: Genetic: Single nucleotide polymorphism (SNP); Other: high performance liquid chromatography; Other: measurements by DXA; Other: questionnaire administration | |
| Exemestane | Blood draws for baseline and six to twelve weeks Receives: Genetic: Single nucleotide polymorphism (SNP); Other: high performance liquid chromatography; Other: measurements by DXA; Other: questionnaire administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Association of single nucleotide polymorphisms with specific quantitative traits (i.e., hormone levels, breast density, and bone mineral density)
Measured: 4 years
Association of haplotype with traits
Measured: 4 years
Secondary outcomes (1)
Association of genomic pathways with traits
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2006 (estimated)
- Study startJul 2005
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- James N. Ingle, MD, Principal investigator, Mayo ClinicEdith A. Perez, MD, Principal investigator, Mayo ClinicDonald W. Northfelt, MD, FACP, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00283608
- Sponsor's protocol ID
- CDR0000583001
- Other IDs
- MC0532, 999-05
- Status last verified
- May 2011
- First submitted
- 27 Jan 2006
- Last updated
- 16 May 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ingle JN, Buzdar AU, Schaid DJ, Goetz MP, Batzler A, Robson ME, Northfelt DW, Olson JE, Perez EA, Desta Z, Weintraub RA, Williard CV, Flockhart DA, Weinshilboum RM. Variation in anastrozole metabolism and pharmacodynamics in women with early breast cancer. Cancer Res. 2010 Apr 15;70(8):3278-86. doi: 10.1158/0008-5472.CAN-09-3024. Epub 2010 Mar 30.
PubMed 20354183Liu M, Goss PE, Ingle JN, Kubo M, Furukawa Y, Batzler A, Jenkins GD, Carlson EE, Nakamura Y, Schaid DJ, Chapman JA, Shepherd LE, Ellis MJ, Khosla S, Wang L, Weinshilboum RM. Aromatase inhibitor-associated bone fractures: a case-cohort GWAS and functional genomics. Mol Endocrinol. 2014 Oct;28(10):1740-51. doi: 10.1210/me.2014-1147. Epub 2014 Aug 22.
PubMed 25148458Liu M, Ingle JN, Fridley BL, Buzdar AU, Robson ME, Kubo M, Wang L, Batzler A, Jenkins GD, Pietrzak TL, Carlson EE, Goetz MP, Northfelt DW, Perez EA, Williard CV, Schaid DJ, Nakamura Y, Weinshilboum RM. TSPYL5 SNPs: association with plasma estradiol concentrations and aromatase expression. Mol Endocrinol. 2013 Apr;27(4):657-70. doi: 10.1210/me.2012-1397. Epub 2013 Mar 21.
PubMed 23518928
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenetics of Aromatase Inhibitors
- ClinicalTrials.gov ID
- NCT00283608
- Acronym / sponsor ID
- CDR0000583001
- Conditions
- Breast Cancer
- Keywords
- stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2005
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 30 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Studying samples of blood in the laboratory from patients with cancer receiving anastrozole may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors learn more about how anastrozole works in the body.
PURPOSE: This research study is looking at the pharmacogenetics of anastrozole in postmenopausal women with estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+) stage I, stage II, or stage III breast cancer.
Detailed description
OBJECTIVES:
- To evaluate the association of intragenic haplotypes in genes encoding proteins involved in anastrozole metabolism pathways with anastrozole steady state plasma levels in postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive stage I, II, or III breast cancer.
- To evaluate the association of intragenic haplotypes in genes that encode proteins involved in pathways for estrogen synthesis, metabolism, and transport and in genes involved in anastrozole metabolism with the pharmacodynamic (PD) effects of anastrozole therapy, as measured by changes (before vs after drug therapy) in plasma levels of estradiol, estrone, estrone sulfate, testosterone, and androstenedione in these patients.
- To evaluate the association of intragenic haplotypes described above with the PD effects of anastrozole therapy, as measured by changes in breast density and bone mineral density before and at 1 year after drug therapy.
- To collect and bank blood samples and mammographic, bone density, and questionnaire data from patients enrolled on CAN-NCIC-MA27 and randomized to receive exemestane.
OUTLINE: This is a multicenter study. Patients are stratified according to prior tamoxifen use (yes vs no).
Blood samples are obtained for pharmacogenetic studies at baseline, at 6-12 weeks, and then at 1 year. Samples are analyzed for plasma anastrozole concentrations via high-performance liquid chromatography; genotyping for htSNPs via PCR; plasma levels of estradiol, estrone, estrone sulfate, testosterone, and androstenedione via gas chromatographic negative chemical ionization tandem mass spectrometry and liquid chromatographic electrospray tandem mass spectrometry.
Mammograms are obtained at baseline (i.e., within the past 6 months) and at 1 year to assess breast density. Patients with bilateral disease, bilateral breast augmentation, or bilateral mastectomy do not participate in this portion of the study.
Patients at the Mayo Clinic Cancer Center Rochester site also undergo bone mineral density measurement via dual x-ray absorptiometry at baseline and at 1 year. Metabolic markers of bone formation and resorption are also assessed in the Mayo Clinic patients.
Blood samples and mammographic, bone mineral density, and questionnaire data collected from patients randomized to receive exemestane on CAN-NCIC-MA27 are stored for future studies.
Patients complete a questionnaire at baseline, at 6-12 weeks, and at 1 year.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anastrozole | – | Genetic: Single nucleotide polymorphism (SNP), Other: high performance liquid chromatography, Other: measurements by DXA, Other: questionnaire administrationBlood draws for baseline and six to twelve weeks. |
| Exemestane | – | Genetic: Single nucleotide polymorphism (SNP), Other: high performance liquid chromatography, Other: measurements by DXA, Other: questionnaire administrationBlood draws for baseline and six to twelve weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Diagnosis of breast cancer. Stage I, II, or III disease. Planning to undergo treatment with anastrozole at the clinically approved dose of 1 mg/day OR Mayo Clinic Cancer Center Rochester patient who will be enrolled on or has been enrolled on CAN-NCIC-MA27 and has not started taking the study medication (anastrozole or exemestane)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Single nucleotide polymorphism (SNP)Evaluating SNP association with traits. | Genetic | Anastrozole, Exemestane |
| high performance liquid chromatographyanalysis of plasma concentrations of drugs | Other | Anastrozole, Exemestane |
| measurements by DXAdetermine bone mineral density (BMD) | Other | Anastrozole, Exemestane |
| questionnaire administrationdetermine attitude changes | Other | Anastrozole, Exemestane |
Primary outcome
Association of single nucleotide polymorphisms with specific quantitative traits (i.e., hormone levels, breast density, and bone mineral density)
Time frame: 4 years
Association of haplotype with traits
Time frame: 4 years
1 secondary outcome
Association of genomic pathways with traits
Time frame: 4 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2011.
- Results publication: PubMed 20354183Ingle JN, Buzdar AU, Schaid DJ, Goetz MP, Batzler A, Robson ME, Northfelt DW, Olson JE, Perez EA, Desta Z, Weintraub RA, Williard CV, Flockhart DA, Weinshilboum RM. Variation in anastrozole metabolism and pharmacodynamics in women with early breast cancer. Cancer Res. 2010 Apr 15;70(8):3278-86. doi: 10.1158/0008-5472.CAN-09-3024. Epub 2010 Mar 30.
- Derived from this study: PubMed 25148458Liu M, Goss PE, Ingle JN, Kubo M, Furukawa Y, Batzler A, Jenkins GD, Carlson EE, Nakamura Y, Schaid DJ, Chapman JA, Shepherd LE, Ellis MJ, Khosla S, Wang L, Weinshilboum RM. Aromatase inhibitor-associated bone fractures: a case-cohort GWAS and functional genomics. Mol Endocrinol. 2014 Oct;28(10):1740-51. doi: 10.1210/me.2014-1147. Epub 2014 Aug 22.
- Derived from this study: PubMed 23518928Liu M, Ingle JN, Fridley BL, Buzdar AU, Robson ME, Kubo M, Wang L, Batzler A, Jenkins GD, Pietrzak TL, Carlson EE, Goetz MP, Northfelt DW, Perez EA, Williard CV, Schaid DJ, Nakamura Y, Weinshilboum RM. TSPYL5 SNPs: association with plasma estradiol concentrations and aromatase expression. Mol Endocrinol. 2013 Apr;27(4):657-70. doi: 10.1210/me.2012-1397. Epub 2013 Mar 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James N. Ingle, MD principal investigator
Mayo Clinic
Edith A. Perez, MD principal investigator
Mayo Clinic
Donald W. Northfelt, MD, FACP principal investigator
Mayo Clinic
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer, run by Mayo Clinic at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Association of single nucleotide polymorphisms with specific quantitative traits (i.e., hormone levels, breast density, and bone mineral density) (time frame: 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00283608, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2011.