A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS)

June 5, 2024 updated by: United States Naval Medical Center, San Diego

E1Z11 A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor, AIMSS

Breast cancer is one of the most prevalent cancers with 207,090 new cases of breast cancer and 39,840 deaths in women predicted for 2010 in the United States. Aromatase inhibitors (AIs) are used as first-line adjuvant therapy for postmenopausal women with early stage breast cancer. The effectiveness of current therapy is widely recognized to be compromised by poor compliance because of aromatase inhibitor-associated musculoskeletal symptoms (AIMSS), a syndrome that affects up to 40-50% of women who take these medications. The syndrome that was not recognized during the registration trials for this class of drugs, it can lead to discontinuation in up to 24% of women over 2 years. Knowledge that can be used to prevent discontinuation of these important agents because of severe AIMSS is urgently needed.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The NCI Division of Cancer Prevention has recognized AIMSS as a priority area for future study. The symptoms are associated with a high rate of AI discontinuation and therefore compromise survival outcomes at great cost to both patients and society. Very little is known about AIMSS, or how to predict who is at risk for the condition, or for discontinuing therapy because of the symptoms. This study will provide a basis for comprehensive assessment of risk factors at the patient-reported outcomes, phenotypic, and laboratory levels. We will explore the natural history of AIMSS in different ethnic populations, and will validate previously reported genetic determinants of the development of AIMSS. A common problem with multicenter GWAS studies of very large sample size, especially in the absence of measurable diagnostic parameters, is inclusion of heterogeneous groups of patients. In addition to assessing pharmacogenomic predictors, this study involves specification of a pre-defined AIMSS phenotype and collection of patient-reported outcomes (PROs). As such, these data will have clinical utility by clarifying the factors associated with aromatase inhibitor discontinuation and thus guiding clinicians towards interventions to improve adherence. Coupled with other studies, the long-term goals are to develop a gene signature that will be used to better guide the selection of endocrine interventions for patients with breast cancer. The underlying physiology of AIMSS remains obscure. A small exploratory case control study did not find a role for commonly encountered cytokines in AIMSS. The role of estrogen and estrogen metabolites remains a possible explanatory variable, as well as new cytokines such as IL-17. This newly described cytokine has been implicated in disorders such as rheumatoid arthritis and other autoimmune diseases, and has been specifically linked to articular nociception in animal models of arthritis. AIMSS Phenotype: The large studies to date of AIs (ATAC, BIG I-98, E1Z03) have been limited by the absence of a clearly defined phenotype for AIMSS. Retrospective analyses have provided some information that clearly cannot replace (PROs). The lack of good prospective PROs represents a major gap as a well-defined phenotype is necessary in order to identify useful genomic associations. Methods evaluating possible predictors such as the use of MRI of the wrists for tenosynovitis are expensive and have not been definitive, and patient-reported symptoms are used and may represent the most useful clinical phenotype.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92134
        • Naval Medical Center San Diego

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

breast cancer patients

Description

Inclusion Criteria:

  • ≥ 60 years of age; or
  • < 60 years of age and amenorrheic for ≥ 12 months prior to day 1 if uterus/ovaries are intact; or
  • < 60 years of age, and the last menstrual period 6-12 months prior to day 1, if intact uterus/ovaries and meets biochemical criteria for menopause (FSH and estradiol within institutional standard for postmenopausal status); or
  • < 60 years of age, without a uterus, and meets biochemical criteria for menopause (FSH and estradiol within institutional standards for postmenopausal status); or
  • < 60 years of age and history of bilateral oophorectomy. Surgery must have been completed at least 4 weeks prior to day 1; or
  • Prior radiation castration with amenorrhea for at least 6 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Caucasian
surveys completed by subject n=600, nationally
Other: surveys completed by subject
Cohort study designed to validate previously identified associations between 10 specific SNPs and discontinuation of treatment with AIs due to the development of MSS among women with breast cancer.
African-American
surveys completed by subject n=200, nationally
Other: surveys completed by subject
Cohort study designed to validate previously identified associations between 10 specific SNPs and discontinuation of treatment with AIs due to the development of MSS among women with breast cancer.
Asian
surveys completed by subject n=200, nationally
Other: surveys completed by subject
Cohort study designed to validate previously identified associations between 10 specific SNPs and discontinuation of treatment with AIs due to the development of MSS among women with breast cancer.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
development of arthritic symptoms
Time Frame: 12 months
patients surveyed and given physical exams
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
United States Naval Medical Center, San Diego

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Alliance for Clinical Trials in Oncology

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Preston Gable, MD, Site PI

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 17, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 19, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 22, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 6, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NMCSD.2014.0053

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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