Aromatase Inhibitor Clinical Trial

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2005 by National Institute of General Medical Sciences (NIGMS).
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Indiana University School of Medicine
Information provided by:
National Institute of General Medical Sciences (NIGMS)
ClinicalTrials.gov Identifier:
NCT00228956
First received: September 27, 2005
Last updated: September 24, 2008
Last verified: September 2005
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: pharmacodynamic analysis
Phase 4

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by NLM:


Further study details as provided by National Institute of General Medical Sciences (NIGMS):

Biospecimen Retention:   Samples With DNA

Whole blood Serum and Plasma Urine


Estimated Enrollment: 500
Study Start Date: January 2005
Estimated Study Completion Date: February 2009
Intervention Details:
    Drug: pharmacodynamic analysis
    Exemestane 25mg po daily or Letrozole 2.5mg po daily
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

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. To measure changes in fasting lipid profiles at baseline and after 3 months of letrozole or exemestane therapy.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Oncology clinics.

Criteria

Inclusion Criteria:

  1. Female gender.
  2. 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,
    • 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.

  3. 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.
  4. ECOG performance status 0-2.
  5. 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.

Exclusion Criteria:

  1. History of bilateral mastectomy.
  2. History of radiation to the contralateral breast.
  3. Prior use of an aromatase inhibitor.
  4. Personal history of the following cancers: ovarian, endometrial, fallopian tube and primary peritoneal carcinomatosis.
  5. Presence of implant in contra-lateral breast.
  6. 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.
  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: NCT00228956

Contacts
Contact: Suzanne Lemler, RN, CCRP 317-274-7841 sulemler@iupui.edu

Locations
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Suzanne Lemler, RN, CCRP    317-274-7841    sulemler@iupui.edu   
Principal Investigator: Anna Maria Storniolo, MD         
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at John Hopkins Not yet recruiting
Baltimore, Maryland, United States, 21231
Contact: Judy Bacon, CCRP    410-502-3613    jbacon1@jhmi.edu   
Principal Investigator: Vered Stearns, MD         
United States, Michigan
UMCCC Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Jill Hayden, RN, CCRC    734-936-8349    jhayden@umich.edu   
Principal Investigator: Daniel Hayes, MD         
Sponsors and Collaborators
Indiana University School of Medicine
Investigators
Principal Investigator: Anna Maria Storniolo, MD Indiana University School of Medicine
  More Information

Additional Information:
No publications provided by National Institute of General Medical Sciences (NIGMS)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00228956     History of Changes
Other Study ID Numbers: 0412-14, UO1-GM61373-06
Study First Received: September 27, 2005
Last Updated: September 24, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institute of General Medical Sciences (NIGMS):
Breast Cancer
Aromatase Inhibitor
Letrozole
Exemestane

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Exemestane
Aromatase Inhibitors
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014