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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cancer and Leukemia Group B
Information provided by (Responsible Party):
Maryam Lustberg, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01478477
First received: November 14, 2011
Last updated: August 2, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention
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
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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Prevention of Aromatase Inhibitor-Induced Joint Symptoms With Omega 3 Fatty Acid Supplementation: a Randomized Placebo Controlled Pilot Study

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Pain score change after 6 months (6 months -baseline) based on the FACT-B/ES instrument [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Pain score change after 6 months (6 months -baseline) based on the HAS and BPI instruments [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    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.

  • Compliance rates with oral supplements (omega-3 fatty acid and placebo) [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
  • Feasibility of using the instruments HAS, BPI-short, FACT-B/ES for the assessment of joint symptoms [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
  • Effectiveness of blinding [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    Summarized using a Chi-square test.

  • Correlation of guess with pain scores [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    Checked using logistic models to see if treatment guesses are explained by the patient's awareness of clinical benefit.

  • Relationship between serum and RBC omega-3 fatty acid levels, inflammatory blood markers and MRI changes and the joint symptoms [ Time Frame: baseline, 6 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 40
Study Start Date: October 2011
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (omega-3 fatty acid supplement)
Omega 3 Polyunsaturated Fatty Acids(n-3 PUFA)
Dietary Supplement: omega-3 fatty acid supplement
6 capsules per day (4.3 g)x 6 months
Other Names:
  • fish oil
  • omega fatty acid
  • O3FA
  • MNSG-194®
  • n-3 PUFA supplementation
Other: 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.
Other Names:
  • Brief Pain Inventory
  • BPI
  • Stanford's Health Assessment-Disability Index
  • HAS
  • FACT-B and endocrine subscale
  • FACT-ES
Other: Assessment of therapy complications
Severity/grade of reaction according to the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
Other Names:
  • adverse events
  • toxicities
  • Expected Toxicities
  • Potential Toxicities
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.
Other Names:
  • MRI
  • NMR imaging
  • NMRI
  • nuclear magnetic resonance imaging
Procedure: 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.
Other Name: laboratory studies
Placebo Comparator: Arm II (placebo)
Typical American Diet oils (TAD)
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.
Other Names:
  • PLCB
  • Typical American Diet oils
  • TAD
Other: 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.
Other Names:
  • Brief Pain Inventory
  • BPI
  • Stanford's Health Assessment-Disability Index
  • HAS
  • FACT-B and endocrine subscale
  • FACT-ES
Other: Assessment of therapy complications
Severity/grade of reaction according to the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
Other Names:
  • adverse events
  • toxicities
  • Expected Toxicities
  • Potential Toxicities
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.
Other Names:
  • MRI
  • NMR imaging
  • NMRI
  • nuclear magnetic resonance imaging
Procedure: 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.
Other Name: laboratory studies
Experimental: Clinical Assessments
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
6 capsules per day (4.3 g)x 6 months
Other Names:
  • fish oil
  • omega fatty acid
  • O3FA
  • MNSG-194®
  • n-3 PUFA supplementation
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.
Other Names:
  • PLCB
  • Typical American Diet oils
  • TAD
Experimental: Assessment of therapy complications
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
6 capsules per day (4.3 g)x 6 months
Other Names:
  • fish oil
  • omega fatty acid
  • O3FA
  • MNSG-194®
  • n-3 PUFA supplementation
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.
Other Names:
  • PLCB
  • Typical American Diet oils
  • TAD
Experimental: Magnetic Resonance Imaging
Optional bilateral hand and wrist MRI imaging will be obtained
Dietary Supplement: omega-3 fatty acid supplement
6 capsules per day (4.3 g)x 6 months
Other Names:
  • fish oil
  • omega fatty acid
  • O3FA
  • MNSG-194®
  • n-3 PUFA supplementation
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.
Other Names:
  • PLCB
  • Typical American Diet oils
  • TAD
Experimental: Correlative/special studies
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
6 capsules per day (4.3 g)x 6 months
Other Names:
  • fish oil
  • omega fatty acid
  • O3FA
  • MNSG-194®
  • n-3 PUFA supplementation
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.
Other Names:
  • PLCB
  • Typical American Diet oils
  • TAD

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01478477

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Cancer and Leukemia Group B
Investigators
Principal Investigator: Maryam Lustberg, MD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Maryam Lustberg, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01478477     History of Changes
Other Study ID Numbers: OSU-11022, NCI-2011-03262
Study First Received: November 14, 2011
Last Updated: August 2, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University Comprehensive Cancer Center:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014