A Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS)
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|ClinicalTrials.gov Identifier: NCT01824836|
Recruitment Status : Active, not recruiting
First Posted : April 5, 2013
Last Update Posted : November 3, 2020
|Condition or disease||Intervention/treatment||Phase|
|Estrogen Receptor-positive Breast Cancer Musculoskeletal Complications Progesterone Receptor-positive Breast Cancer Recurrent Breast Cancer Stage IA Breast Cancer Stage IB Breast Cancer Stage II Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer||Drug: anastrozole Other: questionnaire administration Other: laboratory biomarker analysis Other: pharmacogenomic studies||Not Applicable|
I. To validate previously identified associations between 10 specific single nucleotide polymorphisms (single nucleotide polymorphisms [SNPs]) and discontinuation of treatment with aromatase inhibitors (AIs) due to the development of musculoskeletal symptoms (MSS) among women with breast cancer.
I. To determine whether other SNPs in cytochrome P450 enzymes (CYP), glucuronosyltransferases (UGT), Vitamin D, serotonin and other receptors are associated with discontinuation of treatment due to the development of severe aromatase inhibitor-associated musculoskeletal symptoms (AIMSS).
II. To determine whether other SNPs in CYP, UGT, Vitamin D, serotonin and other receptors are associated with the development of other potential complications of AI therapy.
III. To develop a gene signature that can identify patients at risk for developing severe anastrozole-related AIMSS and other potential complications of AI therapy.
IV. To determine the epidemiology and predictors of severe AIMSS and of AI discontinuation.
V. To describe patient reported outcomes for minority patients with breast cancer treated with AIs.
VI. To assess the utility of the Patient Reported Outcomes Management Information System (PROMIS) system to collect patient reported outcomes in a cooperative group study, and validate the PROMIS Physical Function 20a form in patients with AIMSS.
VII. To develop a model that incorporates patient ratings of treatment burden, fear of recurrence and adherence behaviors to describe patient decisions to continue or discontinue anastrozole.
VIII. To collect serum samples for future testing for biomarkers of AIMSS.
Patients receive anastrozole orally (PO) once daily (QD) for 12 months.
After the completion of study treatment, patients are followed up for 12 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1046 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Supportive Care|
|Official Title:||A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS)|
|Study Start Date :||May 8, 2013|
|Estimated Primary Completion Date :||June 30, 2021|
|Estimated Study Completion Date :||January 2025|
Experimental: Supportive care (anastrozole)
Patients receive anastrozole PO QD for 12 months.
Other: questionnaire administration
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other Name: Pharmacogenomic Study
- Discontinuation of treatment following development of AIMSS determined by scores on the Health Assessment Questionnaire (HAQ) instrument [ Time Frame: Up to 1 year ]Logistic regression will be used to test the association between having a minor allele and the log odds of discontinuation of treatment, adjusting for covariates. A Bonferroni adjustment will be used to account for the simultaneous testing of 10 SNPs; a one-sided p-value of 0.0025 will be considered statistically significant.
- Presence of SNPs in the estrogen receptor alpha (ESR), T-cell leukemia/lymphoma 1A (TCL1A), and CYP19A1 genes [ Time Frame: Up to 1 year ]Correlations among SNPs will be estimated, and linkage disequilibrium among pairs of SNPs will be characterized. Logistic regression models, with treatment discontinuation as the outcome variable, will be used to explore the association with SNPs, adjusting for important clinical factors.
- Proportions of patients with treatment discontinuation for any reason [ Time Frame: Up to 1 year ]Explored using proportional hazards models adjusting for significant genotypic and clinical predictors. Kaplan-Meier plots will be used to graphically portray the associations.
- Proportion of patients with symptoms determined not to be from other known etiologies as assessed by the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) and Breast subscale [ Time Frame: Up to 1 year ]Explored using proportional hazards models adjusting for significant genotypic and clinical predictors. Kaplan-Meier plots will be used to graphically portray the associations.
- Proportion of patients whose symptoms improve when the AI is discontinued [ Time Frame: Up to 1 year ]
- Time to discontinuation of treatment [ Time Frame: Up to 1 year ]Explored using proportional hazards models adjusting for significant genotypic and clinical predictors. Kaplan-Meier plots will be used to graphically portray the associations.
- Time to development of symptoms [ Time Frame: Up to 1 year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01824836
|United States, Massachusetts|
|Eastern Cooperative Oncology Group|
|Boston, Massachusetts, United States, 02215|
|United States, New Jersey|
|Veterans Adminstration New Jersey Health Care System|
|East Orange, New Jersey, United States, 07018-1095|
|Principal Investigator:||Vered Stearns||Eastern Cooperative Oncology Group|