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

Stage IIIA Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01478477
• Other study ID #: OSU-11022
• Secondary ID: NCI-2011-03262
• Status: Completed
• Phase: N/A
• Start date: October 4, 2011
• Est. completion date: January 9, 2014

Study information

• Verified date: February 2023
• Source: Ohio State University Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: January 9, 2014
• Est. primary completion date: January 9, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• 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

Dietary Supplement:
• omega-3 fatty acid supplement
6 capsules per day (4.3 g)x 6 months

Other:
• Placebo
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.
• Clinical assessments
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.
• Assessment of therapy complications
Severity/grade of reaction according to the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE).

Procedure:
• Magnetic Resonance Imaging
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.
• Correlative/special studies
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.

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Ohio State University Comprehensive Cancer Center	Cancer and Leukemia Group B

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Compliance rates with oral supplements (omega-3 fatty acid and placebo)		baseline, 6 months
Secondary	Feasibility of using the instruments HAS, BPI-short, FACT-B/ES for the assessment of joint symptoms		baseline, 6 months
Secondary	Effectiveness of blinding	Summarized using a Chi-square test.	baseline, 6 months
Secondary	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
Secondary	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

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