Breast CancerNCT00228956
Aromatase Inhibitor Clinical Trial
An observational study of Breast Cancer, run by National Institute of General Medical Sciences (NIGMS) at 3 sites in United States.
Trial summary
You are invited to participate in a research study looking at metabolism (breakdown) and effects of aromatase inhibitors. The purpose of this research is to try to identify which women who take an aromatase inhibitor are more likely to have certain benefits or side effects from the drug. Read more about this study
- Who is it for?
- Ages 40 to 70 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- pharmacodynamic analysis
- How many people
- 500 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2005to Feb 2009
- 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 40 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Oncology clinics.
Who may be able to join
- Female gender.
- Post-menopausal status, defined as:
- age > 60; or
- less than age 60 and the last menstrual period >12 months prior to enrollment in trial if intact uterus/ovaries; or,
- less than age 60 and the last menstrual period 6-12 months prior to enrollment in trial if intact uterus/ovaries and meets biochemical criteria for menopause (FSH and estradiol levels within institutional standards for menopausal status) NOTE: These subjects will have serum estradiol levels checked at visits 0, 1, 3, 6 and 12 months to check for continued menopausal status; or,
- less than age 60 and history of bilateral oophorectomy; or,
Show all 13Show fewer
- less than age 60 and has a history of hysterectomy and meets biochemical criteria for menopause (FSH and estradiol levels within institutional standards for menopausal status).
- NOTE: These subjects will have serum estradiol levels checked at visits 0, 1, 3, 6 and 12 months to check for continued menopausal status; or,
- less than age 60 and taking medication designed to suppress ovarian function and meets biochemical criteria for menopause (estradiol levels within institutional standards for menopausal status). Women would have had to be taking the drug for at least 30 days prior to entering the study.
- NOTE: While the patient is being treated with a GnRh agonist (luprolide or goserelin), serum estradiol levels will be checked at visits 0, 1, 3, 6 and 12 months to check for menopausal status.
- Patients with histologically proven ductal carcinoma in situ (DCIS/stage 0) or stage I-III invasive carcinoma of the breast that is ER and/or PR positive by immunohistochemical staining, who are considering aromatase inhibitor therapy. Patients must have completed any adjuvant chemotherapy. Patients may have received preoperative chemotherapy. Patients should have also completed local therapy; however, enrollment/initiation of aromatase inhibitor on study may be done prior to completion of radiation therapy. Women may receive the aromatase inhibitor on this study as initial adjuvant hormonal treatment or following adjuvant tamoxifen.
- ECOG performance status 0-2.
- The patient is aware of the nature of her diagnosis, understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign an informed consent form.
Who cannot join
- History of bilateral mastectomy.
- History of radiation to the contralateral breast.
- Prior use of an aromatase inhibitor.
- Personal history of the following cancers: ovarian, endometrial, fallopian tube and primary peritoneal carcinomatosis.
- Presence of implant in contra-lateral breast.
- Women with history of breast reduction should be entered at the discretion of the investigator. Breast reduction during the two years of the trial is strongly discouraged.
Trial locations and contacts
3 sites in 1 country.
United States3 sites, 3 recruiting
- Not yet recruiting
UMCCC
Ann Arbor, Michigan, 48109
Jill Hayden, RN, CCRC, 734-936-8349, jhayden@umich.edu
Daniel Hayes, MD
- Not yet recruiting
The Sidney Kimmel Comprehensive Cancer Center at John Hopkins
Baltimore, Maryland, 21231
Judy Bacon, CCRP, 410-502-3613, jbacon1@jhmi.edu
Vered Stearns, MD
- Recruiting
Indiana University
Indianapolis, Indiana, 46202
Suzanne Lemler, RN, CCRP, 317-274-7841, sulemler@iupui.edu
Anna Maria Storniolo, MD
About this study
Official title: A Multi-Center Randomized Clinical Trial Correlating the Effects of 24 Months of Exemestane or Letrozole on Surrogate Markers of Response With Aromatase Polymorphism
You are invited to participate in a research study looking at metabolism (breakdown) and effects of aromatase inhibitors. The purpose of this research is to try to identify which women who take an aromatase inhibitor are more likely to have certain benefits or side effects from the drug. We will do so by determining whether there are differences that normally occur in genes that you have inherited from your parents that might influence the way individuals respond to medications. If you agree to participate in this study, you will be asked to sign this informed consent form.
Read the detailed description
Primary Objective To determine baseline breast density and the change in this parameter that occurs in post-menopausal women with hormone-receptor positive primary breast cancer taking letrozole or exemestane for 24 months, and to correlate the changes with wild type or variant aromatase (CYP19).
Secondary Objectives
- To determine serum estrone sulfate concentrations at baseline and following one, three and 24 months of letrozole or exemestane therapy. We will use these concentrations to test the hypothesis that candidate genes involved in estrogen metabolism in post-menopausal women, or in the metabolism and disposition of exemestane or letrozole, influence the ability of aromatase inhibitors to reduce estrogen metabolite concentrations.
- To determine bone density and bone turnover metabolites in post-menopausal women. The bone densitometry will be done at baseline and following 24 months of letrozole or exemestane therapy. The bone turnover metabolites will be done at baseline, three, six and 24 months following letrozole or exemestane therapy. These data will allow us to test the hypothesis that variants in candidate genes involved in estrogen metabolism or signaling alter the ability of exemestane or letrozole to bring about changes in bone.
- To objectively measure hot flashes at baseline and monitor changes in hot flashes after one, three, six and 12 months of letrozole or exemestane therapy, and correlate these changes with serum FSH and LH concentrations. We will test the hypothesis that aromatase or estrogen receptor variants influence the phenotype of hot flashes at baseline or during treatment as part of a broader approach in which we will test for associations with other candidate genes involved in estrogen metabolism and signaling, or with aromatase inhibitor metabolism and disposition.
- To measure changes in symptoms that may be related to hot flashes and estrogen deprivation such as menopausal symptoms, mood (depression, anxiety), sleep quality and sleep disturbance and overall quality of life at baseline and after one, three, six, twelve and 24 months of treatment.
- To measure changes in fasting lipid profiles at baseline and after 3 months of letrozole or exemestane therapy.
- To determine letrozole and exemestane serum concentrations at baseline and after one, three, six, twelve and 24 months of treatment to test the hypothesis that genetic variants in drug metabolizing enzymes predict drug concentrations and effects.
- To measure serum thyroid binding globulin and sex hormone binding globulin concentrations before and after one and three months of treatment, to test whether changes in these parameters brought about by aromatase inhibitor treatment are altered by genetic variants in candidate genes involved in estrogen metabolism or signaling.
- To categorize the rheumatic adverse effects experienced by patients on aromatase inhibitors by specifically characterizing anatomic structures involved and documenting the presence or absence of inflammation in these tissues; to identify any correlations between changes in musculoskeletal symptoms and the duration of therapy with aromatase inhibitors; and to identify any correlations between changes in musculoskeletal symptoms and levels of circulating estrogen and its metabolites. This will be done at baseline and after one, three, six, twelve and 24 months of treatment.
- To determine a number of specific platelet functions before and after 3 months of letrozole and exemestane treatment. This is a sub-study that will be performed only at the Indiana University site. Platelet function will be measured by ex vivo platelet aggregation tests. Production of regulators of platelet function, including thromboxane A2 (TXA2), proscyclin (PGI2) and serotonin will also be assessed. These data will allow us to test the hypothesis that genetic polymorphisms in candidate genes in estrogen-regulated pathways alter the effect of letrozole and exemestane treatment on platelet activity, which may be relevant to their effects on cardiac risks.
- Conditions
- Breast Cancer
- Being tested
- pharmacodynamic analysis
- Keywords
- Breast Cancer, Aromatase Inhibitor, Letrozole, Exemestane
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pharmacodynamic analysisDrug
Exemestane 25mg po daily or Letrozole 2.5mg po daily
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2005 (estimated)
- Study startJan 2005
- Study completionFeb 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of General Medical Sciences (NIGMS)
- Sponsor type
- US National Institutes of Health
- Collaborators
- Indiana University, Office of Research on Women's Health (ORWH), National Institute of Environmental Health Sciences (NIEHS)
- Investigators
- Anna Maria Storniolo, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00228956
- Sponsor's protocol ID
- 0412-14
- Other IDs
- U01GM061373-06
- Status last verified
- Sep 2005
- First submitted
- 27 Sep 2005
- Last updated
- 25 Sep 2008
- Results posted
- No
Publications
Kidwell KM, Harte SE, Hayes DF, Storniolo AM, Carpenter J, Flockhart DA, Stearns V, Clauw DJ, Williams DA, Henry NL. Patient-reported symptoms and discontinuation of adjuvant aromatase inhibitor therapy. Cancer. 2014 Aug 15;120(16):2403-11. doi: 10.1002/cncr.28756. Epub 2014 May 6.
PubMed 24802413Henry NL, Pchejetski D, A'Hern R, Nguyen AT, Charles P, Waxman J, Li L, Storniolo AM, Hayes DF, Flockhart DA, Stearns V, Stebbing J. Inflammatory cytokines and aromatase inhibitor-associated musculoskeletal syndrome: a case-control study. Br J Cancer. 2010 Jul 27;103(3):291-6. doi: 10.1038/sj.bjc.6605768. Epub 2010 Jul 6.
PubMed 20606683Henry NL, Jacobson JA, Banerjee M, Hayden J, Smerage JB, Van Poznak C, Storniolo AM, Stearns V, Hayes DF. A prospective study of aromatase inhibitor-associated musculoskeletal symptoms and abnormalities on serial high-resolution wrist ultrasonography. Cancer. 2010 Sep 15;116(18):4360-7. doi: 10.1002/cncr.25385.
PubMed 20549827Bao T, Fetting J, Mumford L, Zorzi J, Shahverdi K, Jeter S, Herlong F, Stearns V, Lee L. Severe prolonged cholestatic hepatitis caused by exemestane. Breast Cancer Res Treat. 2010 Jun;121(3):789-91. doi: 10.1007/s10549-009-0576-x. Epub 2009 Oct 16. No abstract available.
PubMed 19834799
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center Randomized Clinical Trial Correlating the Effects of 24 Months of Exemestane or Letrozole on Surrogate Markers of Response With Aromatase Polymorphism
- ClinicalTrials.gov ID
- NCT00228956
- Acronym / sponsor ID
- 0412-14
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer, Aromatase Inhibitor, Letrozole, Exemestane
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- National Institute of General Medical Sciences (NIGMS)US National Institutes of Health
- Collaborators
- Indiana University, Office of Research on Women's Health (ORWH), National Institute of Environmental Health Sciences (NIEHS)
- Study start
- Jan 2005
- Study completion
- Feb 2009 (estimated)
- First posted
- 29 Sep 2005 (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.
You are invited to participate in a research study looking at metabolism (breakdown) and effects of aromatase inhibitors. The purpose of this research is to try to identify which women who take an aromatase inhibitor are more likely to have certain benefits or side effects from the drug. We will do so by determining whether there are differences that normally occur in genes that you have inherited from your parents that might influence the way individuals respond to medications. If you agree to participate in this study, you will be asked to sign this informed consent form.
Detailed description
Primary Objective To determine baseline breast density and the change in this parameter that occurs in post-menopausal women with hormone-receptor positive primary breast cancer taking letrozole or exemestane for 24 months, and to correlate the changes with wild type or variant aromatase (CYP19).
Secondary Objectives
- To determine serum estrone sulfate concentrations at baseline and following one, three and 24 months of letrozole or exemestane therapy. We will use these concentrations to test the hypothesis that candidate genes involved in estrogen metabolism in post-menopausal women, or in the metabolism and disposition of exemestane or letrozole, influence the ability of aromatase inhibitors to reduce estrogen metabolite concentrations.
- To determine bone density and bone turnover metabolites in post-menopausal women. The bone densitometry will be done at baseline and following 24 months of letrozole or exemestane therapy. The bone turnover metabolites will be done at baseline, three, six and 24 months following letrozole or exemestane therapy. These data will allow us to test the hypothesis that variants in candidate genes involved in estrogen metabolism or signaling alter the ability of exemestane or letrozole to bring about changes in bone.
- To objectively measure hot flashes at baseline and monitor changes in hot flashes after one, three, six and 12 months of letrozole or exemestane therapy, and correlate these changes with serum FSH and LH concentrations. We will test the hypothesis that aromatase or estrogen receptor variants influence the phenotype of hot flashes at baseline or during treatment as part of a broader approach in which we will test for associations with other candidate genes involved in estrogen metabolism and signaling, or with aromatase inhibitor metabolism and disposition.
- To measure changes in symptoms that may be related to hot flashes and estrogen deprivation such as menopausal symptoms, mood (depression, anxiety), sleep quality and sleep disturbance and overall quality of life at baseline and after one, three, six, twelve and 24 months of treatment.
- To measure changes in fasting lipid profiles at baseline and after 3 months of letrozole or exemestane therapy.
- To determine letrozole and exemestane serum concentrations at baseline and after one, three, six, twelve and 24 months of treatment to test the hypothesis that genetic variants in drug metabolizing enzymes predict drug concentrations and effects.
- To measure serum thyroid binding globulin and sex hormone binding globulin concentrations before and after one and three months of treatment, to test whether changes in these parameters brought about by aromatase inhibitor treatment are altered by genetic variants in candidate genes involved in estrogen metabolism or signaling.
- To categorize the rheumatic adverse effects experienced by patients on aromatase inhibitors by specifically characterizing anatomic structures involved and documenting the presence or absence of inflammation in these tissues; to identify any correlations between changes in musculoskeletal symptoms and the duration of therapy with aromatase inhibitors; and to identify any correlations between changes in musculoskeletal symptoms and levels of circulating estrogen and its metabolites. This will be done at baseline and after one, three, six, twelve and 24 months of treatment.
- To determine a number of specific platelet functions before and after 3 months of letrozole and exemestane treatment. This is a sub-study that will be performed only at the Indiana University site. Platelet function will be measured by ex vivo platelet aggregation tests. Production of regulators of platelet function, including thromboxane A2 (TXA2), proscyclin (PGI2) and serotonin will also be assessed. These data will allow us to test the hypothesis that genetic polymorphisms in candidate genes in estrogen-regulated pathways alter the effect of letrozole and exemestane treatment on platelet activity, which may be relevant to their effects on cardiac risks.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 40 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Oncology clinics.
Key inclusion criteria (13 listed)
- Female gender.
- Post-menopausal status, defined as:
- NOTE: These subjects will have serum estradiol levels checked at visits 0, 1, 3, 6 and 12 months to check for continued menopausal status; or,
- NOTE: While the patient is being treated with a GnRh agonist (luprolide or goserelin), serum estradiol levels will be checked at visits 0, 1, 3, 6 and 12 months to check for menopausal status.
- Patients with histologically proven ductal carcinoma in situ (DCIS/stage 0) or stage I-III invasive carcinoma of the breast that is ER and/or PR positive by immunohistochemical staining, who are considering aromatase inhibitor therapy. Patients must have completed any adjuvant chemotherapy. Patients may have received preoperative chemotherapy. Patients should have also completed local therapy; however, enrollment/initiation of aromatase inhibitor on study may be done prior to completion of radiation therapy. Women may receive the aromatase inhibitor on this study as initial adjuvant hormonal treatment or following adjuvant tamoxifen.
Key exclusion criteria (6 listed)
- History of bilateral mastectomy.
- History of radiation to the contralateral breast.
- Prior use of an aromatase inhibitor.
- Personal history of the following cancers: ovarian, endometrial, fallopian tube and primary peritoneal carcinomatosis.
- Presence of implant in contra-lateral breast.
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 |
|---|---|---|
| pharmacodynamic analysisExemestane 25mg po daily or Letrozole 2.5mg po daily | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2008.
- Derived from this study: PubMed 24802413Kidwell KM, Harte SE, Hayes DF, Storniolo AM, Carpenter J, Flockhart DA, Stearns V, Clauw DJ, Williams DA, Henry NL. Patient-reported symptoms and discontinuation of adjuvant aromatase inhibitor therapy. Cancer. 2014 Aug 15;120(16):2403-11. doi: 10.1002/cncr.28756. Epub 2014 May 6.
- Derived from this study: PubMed 20606683Henry NL, Pchejetski D, A'Hern R, Nguyen AT, Charles P, Waxman J, Li L, Storniolo AM, Hayes DF, Flockhart DA, Stearns V, Stebbing J. Inflammatory cytokines and aromatase inhibitor-associated musculoskeletal syndrome: a case-control study. Br J Cancer. 2010 Jul 27;103(3):291-6. doi: 10.1038/sj.bjc.6605768. Epub 2010 Jul 6.
- Derived from this study: PubMed 20549827Henry NL, Jacobson JA, Banerjee M, Hayden J, Smerage JB, Van Poznak C, Storniolo AM, Stearns V, Hayes DF. A prospective study of aromatase inhibitor-associated musculoskeletal symptoms and abnormalities on serial high-resolution wrist ultrasonography. Cancer. 2010 Sep 15;116(18):4360-7. doi: 10.1002/cncr.25385.
- Derived from this study: PubMed 19834799Bao T, Fetting J, Mumford L, Zorzi J, Shahverdi K, Jeter S, Herlong F, Stearns V, Lee L. Severe prolonged cholestatic hepatitis caused by exemestane. Breast Cancer Res Treat. 2010 Jun;121(3):789-91. doi: 10.1007/s10549-009-0576-x. Epub 2009 Oct 16. No abstract available.
- The Pharmacogenetics and Pharmacogenomics Knowledge BaseLink provided by the sponsor.
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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.
Anna Maria Storniolo, MD principal investigator
Indiana University
3 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 National Institute of General Medical Sciences (NIGMS) at 3 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?
The sponsor lists 13 inclusion and 6 exclusion criteria. 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: status not confirmed, as of the sponsor's last update on 25 Sep 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Suzanne Lemler, RN, CCRP (317-274-7841, sulemler@iupui.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00228956, which also lists 4 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 25 Sep 2008.