Trial Information

S0927: A Randomized Placebo-Controlled Trial of Omega-3-Fatty Acid for the Control of Aromatase Inhibitor-Induced Musculoskeletal Pain and Stiffness In Women With Early Stage Breast Cancer, Phase III

OBJECTIVES:

Primary

- To assess whether omega-3-fatty acid as compared to placebo causes a reduction in worst
joint pain and/or stiffness at 12 weeks, as measured by the modified Brief Pain
Inventory (BPI), in women with early-stage breast cancer and aromatase inhibitor
(AI)-associated arthralgia.

Secondary

- To assess the proportion of patients who report improved versus deteriorated joint pain
with omega-3-fatty acid versus placebo.

- To assess the proportion of patients who report improved versus deteriorated joint
stiffness with omega-3-fatty acid versus placebo.

- To assess whether patients receiving omega-3-fatty acid compared to placebo have
decreased analgesic use and increased AI adherence.

- To assess whether patients receiving omega-3-fatty acid compared to placebo have
improved functioning, pain, and stiffness in the knees/hips (as measured by the Western
Ontario and McMaster Universities Osteoarthritis, WOMAC) score.

- To assess whether patients receiving omega-3-fatty acid have improved functioning,
pain, and stiffness in the hands (as measured by the Modified Score for the Assessment
and Quantification of Chronic Rheumatoid Affections of the Hands, M-SACRAH).

- To assess whether patients receiving omega-3-fatty acid compared to placebo have
improved functional quality of life as measured by the Functional Assessment of Cancer
Therapy-Endocrine Subscale (FACT-ES) Trial Outcome Index (TOI).

- To assess whether patients receiving omega-3-fatty acid report changes for the better
versus worse compared to placebo as measured by the Global Rating of Change Scale.

- To identify minimally important change in the WOMAC, M-SACRAH, and the FACT-ES Trial
Outcome Index (TOI) using "a little better" or "a little worse" responses on the
patient-reported global rating of change in joint pain and joint stiffness.

- To assess whether patients receiving omega-3-fatty acid compared to placebo have an
improved lipid profile as measured by triglycerides, HDL, and LDL.

- To assess the toxicity of omega-3-fatty acid compared to placebo in this setting.

- To assess whether there is a difference in serum-free and total estradiol levels before
and after treatment with omega-3-fatty acid compared to placebo.

- To explore whether CYP19A1 genotype correlates with severity of joint symptoms or
predicts response to omega-3-fatty acid. (exploratory)

- To explore changes in hormonal and inflammatory serum biomarkers, such as IL6, TNF-α,
and CRP.

- To assess whether there is a relationship between change in serum docosahexaenoic acid
(DHA) and EPA and resolution of joint symptoms.

- To establish a cohort of patients (placebo group) to better characterize the natural
history of the syndrome.

OUTLINE: This is a multicenter study. Patients are stratified according to prior
osteoarthritis (yes vs no) and prior taxane use (yes vs no). Patients are randomized to 1 of
2 treatment arms.

- Arm I: Patients receive oral omega-3-fatty acid twice daily (BID) or three times daily
(TID) for 24 weeks in the absence of disease progression or unacceptable toxicity.

- Arm II: Patients receive oral placebo BID or TID for 24 weeks in the absence of disease
progression or unacceptable toxicity.

Patients undergo blood sample collection at baseline and at 12 and 24 weeks for biomarker
and DNA analysis.

Patients complete the Brief Pain Inventory Short Form (BPI-SF), the Western Ontario and
McMaster Universities Osteoarthritis (WOMAC) Index, the Modified-Score for the Assessment
and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH), the FACT-ES
Trial Outcome Index, and the Omega-3-fatty acid Dietary Intake questionnaires at baseline
and at 6, 12, and 24 weeks.