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

NCT01824836 | Active Not Recruiting Results DMC FDA Drug

• 3 other identifiers: E1Z11NCI-2013-00426U10CA037403
• Study Type: interventional
• Target: 1,046
• Locations: 1 country
• Sites: 2

Brief Summary

E1Z11 is a study to determine whether certain genetic information can predict which breast cancer patients will discontinue treatment with aromatase inhibitors (AIs) due to the development of musculoskeletal symptoms (MSS). Women with stage I-III breast cancer who are prescribed the aromatase inhibitor anastrozole as treatment may join.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Associations Between Pre-specified Single Nucleotide Polymorphisms (SNPs) and Discontinuation of Treatment With Aromatase Inhibitor (AI) Due to the Development of Musculoskeletal Symptoms (MSS)

  Patients were classified into two groups based on whether or not they discontinued treatment due to MSS within 12 months. The 10 SNPs evaluated include ESR1 (rs2234693, rs2347868, rs9340835), CYP19A1 (rs1062033, rs4646), TCL1A (rs11849538, rs2369049, rs7158782, rs7159713), and HTR2A (rs2296972). The associations between SNPs and discontinuation of treatment due to AIMSS are presented by odds ratios (ORs). An OR of 1 suggests no association, while an OR \> 1 indicates a greater chance of treatment discontinuation in the one group compared to the reference group, and an OR \< 1 suggests a lower chance.

  Assessed at baseline and 3, 6, 9, 12 months

Secondary Outcomes (10)

• Associations Between Other SNPs in CYP, UGT, Vitamin D, Serotonin and Other Receptors and Discontinuation of Treatment Due to the Development of Severe AIMSS

  Assessed at baseline and 3, 6, 9, 12 months

• Associations Between Development of Other Potential Complications of AI Therapy and Other SNPs in CYP, UGT, Vitamin D, Serotonin and Other Receptors

  Assessed at baseline, and 3, 6, 9, 12 months

• The Distribution of the Development of AIMSS by Genotype of the rs2296972 SNP

  Assessed at baseline, and 3, 6, 9, 12 months

• The Distribution of Development of AIMSS by Race

  Assessed at baseline, and 3, 6, 9, 12 months

• Patient Reported Outcomes (Health Assessment Questionnaire [HAQ] Pain Scores) at Baseline for Patients With Breast Cancer Treated With Aromatase Inhibitors (AIs).

  Assessed at baseline

Other Outcomes (2)

• To Assess the Utility of the Reported Outcomes Management Information System (PROMIS) to Collect Patient Reported Outcomes in a Cooperative Group Study, and Validate the PROMIS Physical Function 20a Form in Patients With AIMSS

  Assessed at baseline, diagnosis of AIMSS, discontinuation of treatment due to AIMSS, one month after treatment discontinuation due to AIMSS, and 3, 6, 9, 12 months

• To Collect Serum Samples for Future Testing for Biomarkers of AIMSS

  Assessed at baseline, diagnosis of AIMSS, discontinuation of treatment due to AIMSS, one month after treatment discontinuation due to AIMSS, and 3, 6, 9, 12 months

Study Arms (1)

Supportive care (anastrozole)

EXPERIMENTAL

Patients receive anastrozole PO QD for 12 months.

Drug: anastrozole

Interventions

anastrozole DRUG

Given PO

Also known as: Arimidex

Supportive care (anastrozole)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be post-menopausal; post-menopausal will be defined as women meeting any of the following 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 (follicle-stimulating hormone \[FSH\] 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
• Patients must have estrogen and/or progesterone receptor positive histologically confirmed stage I-III adenocarcinoma of the breast
• Patients must have completed recommended local therapy and adjuvant chemotherapy for breast cancer
• Plan to treat with anastrozole for at least 12 months
• Eastern Cooperative Oncology Group (ECOG) performance status between 0-2
• Patients must be disease-free of other prior invasive malignancies for ≥ 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. Prior early stage breast cancers are also allowed as long as prior treatment did not include aromatase inhibitors.
• Patients must have worst pain rated as less than 4 out of 10 on the following question: "In the past week, how much pain have you had on a scale of 0 to 10, where 0 equals no pain and 10 means the worst pain you can imagine; " NOTE: This question regarding patient's pain should be completed within one week prior to registration; this pain item may be completed orally prior to consent up to 7 days prior to registration; it is not necessary to complete this pain item via the PROMIS website
• Patients must have adequate hepatic, hematologic and renal functioning to be able to be administered anastrozole at the discretion of the treating physician

You may not qualify if:

• Prior AI therapy with exemestane, letrozole, or anastrozole as adjuvant therapy or for prevention of breast cancer; prior tamoxifen as adjuvant therapy or for prevention is allowed
• Patients must not be currently taking (or have taken in the past 6 months) ongoing, daily analgesic medication for active, chronic conditions (i.e., rheumatoid arthritis, carpal tunnel syndrome, tenosynovitis, systemic lupus erythematosus, gout, fibromyalgia, or severe osteoarthritis involving the hands, wrists, hips, knees, feet or ankles); (note: patients taking daily low dose aspirin are allowed to participate in this trial)
• Prior history of deep vein thrombosis (DVT) or pulmonary embolism in the past 5 years

Sponsors & Collaborators

• ECOG-ACRIN Cancer Research Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Eastern Cooperative Oncology Group

Boston, Massachusetts, 02215, United States

Location

Veterans Adminstration New Jersey Health Care System

East Orange, New Jersey, 07018-1095, United States

Location

Related Publications (1)

• Stearns V, Jegede OA, Chang VT, Skaar TC, Berenberg JL, Nand R, Shafqat A, Jacobs NL, Luginbuhl W, Gilman P, Benson AB 3rd, Goodman JR, Buchschacher GL Jr, Henry NL, Loprinzi CL, Flynn PJ, Mitchell EP, Fisch MJ, Sparano JA, Wagner LI. A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms: Results from ECOG-ACRIN E1Z11. Clin Cancer Res. 2024 Jul 1;30(13):2709-2718. doi: 10.1158/1078-0432.CCR-23-2137.

  PMID: 38640040 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Statistical Office

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• Vered Stearns

  Eastern Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2013
• First Posted: April 5, 2013
• Study Start: June 11, 2013
• Primary Completion: June 9, 2022
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 31, 2025
• Results First Posted: April 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

US (2)