Clinical trial NCT01824836: A Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS)
Official title: A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
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
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-04-05
Enrollment: 1046
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Associations Between Pre-specified Single Nucleotide Polymorphisms (SNPs) and Discontinuation of Treatment With Aromatase Inhibitor (AI) Due to the Development of Musculoskeletal Symptoms (MSS)
timeFrame: Assessed at baseline and 3, 6, 9, 12 months
Secondary outcomes:
measure: Associations Between Other SNPs in CYP, UGT, Vitamin D, Serotonin and Other Receptors and Discontinuation of Treatment Due to the Development of Severe AIMSS
timeFrame: Assessed at baseline and 3, 6, 9, 12 months
measure: Associations Between Development of Other Potential Complications of AI Therapy and Other SNPs in CYP, UGT, Vitamin D, Serotonin and Other Receptors
timeFrame: Assessed at baseline, and 3, 6, 9, 12 months
measure: The Distribution of the Development of AIMSS by Genotype of the rs2296972 SNP
timeFrame: Assessed at baseline, and 3, 6, 9, 12 months
measure: The Distribution of Development of AIMSS by Race
timeFrame: Assessed at baseline, and 3, 6, 9, 12 months
measure: Patient Reported Outcomes (Health Assessment Questionnaire [HAQ] Pain Scores) at Baseline for Patients With Breast Cancer Treated With Aromatase Inhibitors (AIs).
timeFrame: Assessed at baseline
measure: Patient Reported Outcomes (Health Assessment Questionnaire [HAQ] Pain Scores) at 3 Months for Patients With Breast Cancer Treated With Aromatase Inhibitors (AIs).
timeFrame: Assessed at 3 months
measure: Patient Reported Outcomes (Health Assessment Questionnaire [HAQ] Pain Scores) at 6 Months for Patients With Breast Cancer Treated With Aromatase Inhibitors (AIs).
timeFrame: Assessed at 6 months
measure: Patient Reported Outcomes (Health Assessment Questionnaire [HAQ] Pain Scores) at 9 Months for Patients With Breast Cancer Treated With Aromatase Inhibitors (AIs).
timeFrame: Assessed at 9 months
measure: Patient Reported Outcomes (Health Assessment Questionnaire [HAQ] Pain Scores) at 12 Months for Patients With Breast Cancer Treated With Aromatase Inhibitors (AIs).
timeFrame: Assessed at 12 months
measure: 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
timeFrame: 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
Other outcomes:
measure: 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
timeFrame: 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
measure: To Collect Serum Samples for Future Testing for Biomarkers of AIMSS
timeFrame: 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
Locations:
city: Boston
country: United States
facility: Eastern Cooperative Oncology Group
state: Massachusetts
city: East Orange
country: United States
facility: Veterans Adminstration New Jersey Health Care System
state: New Jersey
Study officials:
affiliation: Eastern Cooperative Oncology Group
name: Vered Stearns
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.