Omega-3 Fatty Acids in Preventing Joint Symptoms in Patients With Stage I-III Breast Cancer Receiving Anastrozole, Exemestane, or Letrozole

Study Overview
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Brief Summary
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This randomized pilot trial studies omega-3 fatty acid in preventing joint symptoms in patients with stage I-III breast cancer receiving anastrozole, exemestane, or letrozole. Omega-3 fatty acid supplement may lessen or prevent joint stiffness or pain in patients receiving hormone therapy for breast cancer.

Detailed Description
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OBJECTIVES: I. To assess the feasibility of evaluating joint symptoms in postmenopausal women with breast cancer randomized to n-3 PUFA (omega-3 fatty acid) vs. placebo supplementation using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and endocrine subscale (FACT-ES), Brief Pain Inventory (BPI) and Stanford's Health Assessment -Disability Index (HAS) during the first 6 months of adjuvant aromatase inhibitor (AI) therapy. II. To preliminarily evaluate the efficacy of n-3 PUFA vs. placebo supplementation on AI induced joint symptoms. III. To explore blood and imaging based biomarkers (plasma and red blood cell [RBC] levels of n-3 PUFAs, inflammatory cytokines and receptors, and intra-articular tenosynovial inflammation by musculoskeletal magnetic resonance imaging [MRI] imaging) of AI-induced joint symptoms in women on AI therapy randomized to n-3 PUFAs vs. placebo supplementation. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive omega-3 fatty acid orally (PO) once daily (QD) for 6 months in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity.

Official Title
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Prevention of Aromatase Inhibitor-Induced Joint Symptoms With Omega 3 Fatty Acid Supplementation: a Randomized Placebo Controlled Pilot Study

Conditions
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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

Intervention / Treatment
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* Dietary Supplement: omega-3 fatty acid supplement
* Other: Placebo
* Other: Clinical assessments
* Other: Assessment of therapy complications
* Procedure: Magnetic Resonance Imaging
* Procedure: Correlative/special studies


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women diagnosed with breast cancer stages I-III initiating first adjuvant AI therapy with any of the Food and Drug Administration- (FDA) approved AIs (anastrozole, 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 History of osteoarthritis and/or fibromyalgia 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, with the exception of osteoarthritis and fibromyalgia AI use > 2 weeks prior to study enrollment Known bleeding disorders History of diabetes mellitus, heart disease or TIA/stroke 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 regular or any other supplements that might interact with n-3 PUFA supplements within six months of study initiation; sporadic use of n-3 PUFA supplement may be eligible if there has been a 3-month washout period prior to randomization Pregnant or nursing women Known sensitivity or allergy to fish or fish oil Concurrent use of daily full dose aspirin (≥ 325 mg/day), nonsteroidal anti-inflammatory drugs (NSAIDs) or NSAID-containing products or steroids; one month washout period is required prior to randomization Unable to give informed consent In patients consenting for optional MRIs, any contraindication to MRI examination including but not limited to ferromagnetic metal in the body, pacemaker, or severe claustrophobia

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (omega-3 fatty acid supplement)<br>Omega 3 Polyunsaturated Fatty Acids(n-3 PUFA) | Dietary Supplement: omega-3 fatty acid supplement<br>* 6 capsules per day (4.3 g)x 6 months<br>* Other names: n-3 PUFA supplementation;Other: Clinical assessments<br>* All three instruments will be administered at baseline, at 3 months, 6 months and at additional time intervals when there is a significant change in therapy (discontinuation/switch, pain medication administration) during routine medical oncology visits.<br>* Other names: FACT-ES;Other: Assessment of therapy complications<br>* Severity/grade of reaction according to the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE).<br>* Other names: Potential Toxicities;Procedure: Magnetic Resonance Imaging<br>* Optional bilateral hand and wrist MRI imaging will be obtained at baseline and at 6 months to eligible patients who have no contraindications to MRI imaging.<br>* Other names: nuclear magnetic resonance imaging;Procedure: Correlative/special studies<br>* Plasma, RBC, and serum samples from the baseline blood draw will also be stored at -70C for fatty acid and biomarker analyses and repeated at 3 month and 6 month intervals. Samples will be analyzed in batches every 6 months.<br>* Other names: laboratory studies;|
| Placebo Comparator: Arm II (placebo)<br>Typical American Diet oils (TAD) | Other: Placebo<br>* 6 capsules per day (4.3 g)x 6 months. Supplement should be taken with food once per day. No specific food requirements are needed.<br>* Other names: TAD;Other: Clinical assessments<br>* All three instruments will be administered at baseline, at 3 months, 6 months and at additional time intervals when there is a significant change in therapy (discontinuation/switch, pain medication administration) during routine medical oncology visits.<br>* Other names: FACT-ES;Other: Assessment of therapy complications<br>* Severity/grade of reaction according to the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE).<br>* Other names: Potential Toxicities;Procedure: Magnetic Resonance Imaging<br>* Optional bilateral hand and wrist MRI imaging will be obtained at baseline and at 6 months to eligible patients who have no contraindications to MRI imaging.<br>* Other names: nuclear magnetic resonance imaging;Procedure: Correlative/special studies<br>* Plasma, RBC, and serum samples from the baseline blood draw will also be stored at -70C for fatty acid and biomarker analyses and repeated at 3 month and 6 month intervals. Samples will be analyzed in batches every 6 months.<br>* Other names: laboratory studies;|
| Experimental: Clinical Assessments<br>Brief Pain Inventory (BPI), Stanford's Health Assessment-Disability Index (HAS), FACT-B and endocrine subscale (FACT-ES) | Dietary Supplement: omega-3 fatty acid supplement<br>* 6 capsules per day (4.3 g)x 6 months<br>* Other names: n-3 PUFA supplementation;Other: Placebo<br>* 6 capsules per day (4.3 g)x 6 months. Supplement should be taken with food once per day. No specific food requirements are needed.<br>* Other names: TAD;|
| Experimental: Assessment of therapy complications<br>Adverse events will be monitored by self-reporting of signs and symptoms. Patients will maintain a daily diary of time of supplement intake and any possible ill effects, with instructions to contact the PI or Research Nurse to discuss and manage any possible side effects. | Dietary Supplement: omega-3 fatty acid supplement<br>* 6 capsules per day (4.3 g)x 6 months<br>* Other names: n-3 PUFA supplementation;Other: Placebo<br>* 6 capsules per day (4.3 g)x 6 months. Supplement should be taken with food once per day. No specific food requirements are needed.<br>* Other names: TAD;|
| Experimental: Magnetic Resonance Imaging<br>Optional bilateral hand and wrist MRI imaging will be obtained | Dietary Supplement: omega-3 fatty acid supplement<br>* 6 capsules per day (4.3 g)x 6 months<br>* Other names: n-3 PUFA supplementation;Other: Placebo<br>* 6 capsules per day (4.3 g)x 6 months. Supplement should be taken with food once per day. No specific food requirements are needed.<br>* Other names: TAD;|
| Experimental: Correlative/special studies<br>Enrolled participants will have peripheral blood samples drawn for plasma and RBC n-3 PUFA levels within 4 weeks of starting AI therapy. | Dietary Supplement: omega-3 fatty acid supplement<br>* 6 capsules per day (4.3 g)x 6 months<br>* Other names: n-3 PUFA supplementation;Other: Placebo<br>* 6 capsules per day (4.3 g)x 6 months. Supplement should be taken with food once per day. No specific food requirements are needed.<br>* Other names: TAD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain score change after 6 months (6 months -baseline) based on the FACT-B/ES instrument | Pain scores based on FACT-B/ES, HAS and BPI will be plotted over time for each arm. Agreement between HAS, BPI-short and FACT-B/ES evaluated using Altman and Bland plot after proper data transformation. Also, Linear Mixed model used to explore if the pain scores are different at 3 and 6 months. Logistic regression models used to compare the occurrence of moderate to severe joint symptoms during the 6 month period between the two treatment groups, with potential covariates including age, body mass index, baseline pain scores (0 month), prior chemotherapy and other variables. | baseline, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain score change after 6 months (6 months -baseline) based on the HAS and BPI instruments | Agreement between HAS, BPI-short and FACT-B/ES evaluated using Altman and Bland plot after proper data transformation. Also, Linear Mixed model used to explore if the pain scores are different at 3 and 6 months. Logistic regression models used to compare the occurrence of moderate to severe joint symptoms during the 6 month period between the two treatment groups, with potential covariates including age, body mass index, baseline pain scores (0 month), prior chemotherapy and other variables. | baseline, 6 months | 
| Compliance rates with oral supplements (omega-3 fatty acid and placebo) |  | baseline, 6 months | 
| Feasibility of using the instruments HAS, BPI-short, FACT-B/ES for the assessment of joint symptoms |  | baseline, 6 months | 
| Effectiveness of blinding | Summarized using a Chi-square test. | baseline, 6 months | 
| Correlation of guess with pain scores | Checked using logistic models to see if treatment guesses are explained by the patient's awareness of clinical benefit. | baseline, 6 months | 
| Relationship between serum and RBC omega-3 fatty acid levels, inflammatory blood markers and MRI changes and the joint symptoms | Scatter plots and correlation coefficients (either Pearson or Spearman) will be used to summarize their pair wise relation. The differences between the treatment and placebo in terms of these measures will also be reported using numerical summaries and graphic plots. | baseline, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer