Omega-3 Supplementation in Prevention of Aromatase Inhibitor-Induced Toxicity in Patients With Stage I-III Breast Cancer

Study Overview
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Brief Summary
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This clinical trial studies the use of omega-3 fatty acid supplementation in preventing aromatase inhibitor-induced toxicity in patients with stage I-III breast cancer. An omega-3 supplementation may help relieve moderate to severe bone pain and improve joint symptoms caused by aromatase inhibitor-induced arthralgias.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the efficacy of the complementary therapy omega-3 fatty acid (n-3 PUFA) supplementation in preventing aromatase inhibitor-induced arthralgias (AIIAs). SECONDARY OBJECTIVES: I. To prospectively define the population most at risk for developing AIIAs by the identification and validation of genetic risk predictors and to develop a single nucleotide polymorphism (SNP)/gene profile predictive of treatment intervention response. OUTLINE: Patients are randomized to 1 of 2 groups. Group I: Patients receive omega-3 fatty acid supplementation orally (PO) once daily (QD) for 6 months. Group II: Patients receive placebo PO QD for 6 months. After completion of study, patients will be followed up periodically.

Official Title
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Prevention of Aromatase Inhibitor-Induced Toxicity With Omega-3 Supplementation

Conditions
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Arthralgia, Breast Neoplasms

Intervention / Treatment
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* Dietary Supplement: Omega-3 Fatty Acid
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women diagnosed with breast cancer stages I-III initiating first line adjuvant aromatase inhibitor (AI) therapy with any of the FDA-approved AIs (anastrazole, exemestane, letrozole) Concurrent gonadotropin-releasing hormone (GnRH) agonist therapy is allowed; concurrent breast related radiation therapy is allowed. Prior tamoxifen use is allowed Prior chemotherapy is allowed Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Metastatic malignancy of any kind Rheumatoid arthritis and other types of autoimmune and inflammatory joint disease AI use > 21 days prior to study enrollment Known bleeding disorders Current use of warfarin or other anticoagulants Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements Daily use of n-3 PUFA concentrates or capsules or any other supplements that might interact with n-3 PUFA supplements if > 375 mg per day of of eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA) within six months of study initiation Pregnant or nursing women Known sensitivity or allergy to fish or fish oil Unable to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (omega-3 fatty acid)<br>Patients receive omega-3 fatty acid supplementation PO QD for 6 months. | Dietary Supplement: Omega-3 Fatty Acid<br>* Given PO.<br>* Other names: omega-3-Fatty Acids;|
| Placebo Comparator: Arm II (placebo)<br>Patients receive placebo PO QD for 6 months. | Other: Placebo<br>* Given PO.<br>* Other names: sham therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain score based on the Brief Pain Inventory (BPI) | Analysis of patterns of change over time in pain scores through the application of hierarchical linear regression models. | Baseline to up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in joint symptoms based on quality of life instruments | An exploratory analysis, logistic mixed effect regression models will be used to compare the occurrence of moderate to severe joint symptoms during the 6 month period between the two treatment groups. | Baseline to up to 6 months | 
| Change in joint symptoms based on symptomatology instruments | An exploratory analysis, logistic mixed effect regression models will be used to compare the occurrence of moderate to severe joint symptoms during the 6 month period between the two treatment groups. | Baseline to up to 6 months | 
| Identification and validation of genetic risk predictors for aromatase inhibitor-induced arthralgias | Interaction tests between treatment and stratification variables will be conducted to explore whether these factors are predictive of average pain scores. | Up to 6 months | 
| Rate of compliance | The rates of adherence to and discontinuation of AI therapy will be recorded. Reasons for treatment discontinuation will be described. In addition, the investigators will also examine the compliance rates with n-3 PUFA or placebo supplements with pill counts at each visit and with a patient recorded medication calendar. | Up to 6 months | 
| SNP analysis by standard data preprocessing operations and sequential analysis | A sequential analysis of the data that allows filtering of extraneous SNPs and select SNP loci, identification and creation of predictive SNP clusters, and then evaluation of the networks' potential clinical and biological validity will be performed. | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stage IIA, Breast Cancer, Postmenopausal, Stage IA, Stage IB, Stage IIB, Stage IIIA, Stage IIIB, Stage IIIC