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

NCT ID: NCT01824836

Last Updated: 2025-05-31

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 1046 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-11
• Study Completion Date: 2026-12-31

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.

Detailed Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

OUTLINE:

Patients receive anastrozole orally (PO) once daily (QD) for 12 months.

After the completion of study treatment, patients are followed up for 12 months.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Supportive care (anastrozole)

Patients receive anastrozole PO QD for 12 months.

Group Type: EXPERIMENTAL

anastrozole

Intervention Type: DRUG

Given PO

Interventions

anastrozole

Given PO

Intervention Type: DRUG

Other Intervention Names

Arimidex

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

ECOG-ACRIN Cancer Research Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vered Stearns

Role: PRINCIPAL_INVESTIGATOR

Eastern Cooperative Oncology Group

Locations

Eastern Cooperative Oncology Group

Boston, Massachusetts, United States

Veterans Adminstration New Jersey Health Care System

East Orange, New Jersey, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 38640040 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2013-00426

Identifier Type: REGISTRY

Identifier Source: secondary_id

U10CA037403

Identifier Type: NIH

Identifier Source: secondary_id

View Link

E1Z11

Identifier Type: -

Identifier Source: org_study_id