Clinical trial NCT04268134: Altering Lipids for Tolerance of Aromatase Inhibitor Therapy
Official title: Omega-3 Fatty Acids, Oxylipins, and Tolerance of Aromatase Inhibitor Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Aromatase inhibitor
Omega-3 fatty acid
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2020-02-13
Enrollment: 77
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: Aromatase inhibitor medications have been approved by the U.S Food and Drug Administration (FDA) for treatment of hormone receptor positive breast cancer. This treatment has been shown to be very effective for treating breast cancer. However, some patients have difficulty tolerating the treatment, and some even decide to stop treatment because of the side effects. Research has shown that over half of patients who had joint pain and stiffness when taking an aromatase inhibitor had an improvement in their symptoms when they took omega-3 fatty acid supplements. This study is being conducted to test whether having patients start to take an omega-3 fatty acid supplement soon after they starting taking an aromatase inhibitor medicine will reduce the likelihood that they will have bothersome symptoms.


Eligibility criteria: Inclusion Criteria

* Female subject aged ≥ 18 years who are postmenopausal according to standard clinical criteria or who will have been receiving LHRH agonist therapy for at least 28 days prior to AI initiation.
* Stage 0-3 estrogen receptor positive (≥1%) and/or progesterone receptor positive (≥1%) breast cancer, or patients at high risk of developing breast cancer who are planning to initiate AI therapy for chemoprevention.
* Planned initiation of aromatase inhibitor therapy (anastrozole, exemestane, or letrozole) for adjuvant treatment of breast cancer or for chemoprevention up to 30 days following baseline visit (ok to initiate screening up to 2 months before planned baseline visit). Concurrent LHRH agonist, anti-HER2 directed therapy (e.g., trastuzumab, pertuzumab, ado-trastuzumab emtansine), and/or CDK4/6 inhibitor therapy (e.g., palbociclib, ribociclib, abemaciclib) is permitted. Prior tamoxifen and/or toremifene is permitted.
* Completion of surgery (mastectomy or lumpectomy/partial mastectomy) for treatment of breast cancer. Completion of axillary surgery as indicated (not required). For patients at high risk of breast cancer who have not been diagnosed with breast cancer, no surgery is required.
* Completion of chemotherapy, if indicated. Concurrent use of radiation therapy, LHRHa therapy, anti-HER2 therapy, PARP inhibitor, and CDK4/6 inhibitor therapy is permitted. Prior tamoxifen is permitted.
* Agree to avoid taking omega-3 fatty acid supplements from sources outside the trial during study participation.
* ECOG Performance Status ≤ 3.
* Able to complete questionnaires in English.
* Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria

* Prior use of AI therapy for treatment or prevention of breast cancer.
* Use of omega-3 fatty acid supplementation during the 3 months prior to enrollment. Consumption of O3-FA through diet is permitted.
* Use of warfarin, enoxaparin, or direct oral anticoagulants within 7 days prior to registration.
* Known chronic liver disease (laboratory studies will not be assessed). Patients with hepatosteatosis, viral hepatitis, or other liver disorders who have adequate liver function according to the treating physician are permitted to enroll.
* Known symptomatic paroxysmal atrial fibrillation or persistent atrial fibrillation (EKGs will not be performed).
* History of pancreatitis.
* Hypersensitivity to fish and/or shellfish.
* Unable to take oral medications.
* Any medical condition that would interfere with the absorption of study medication capsules.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not, in the opinion of the treating investigator, have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Primary outcomes:
measure: Change in percentage of total fatty acids for each polyunsaturated fatty acid (PUFA) group from start of Omega-3 Fatty Acid (O3-FA) supplementation to 3 months of O3-FA
timeFrame: From start of Omega-3 Fatty Acid (O3-FA) supplementation to 3 months of O3-FA (at 6 months after start of AI therapy)
Secondary outcomes:
measure: Change in percentage of total fatty acids for each PUFA group from baseline to 6 months of Aromatase Inhibitor (AI) (3 months of AI alone + 3 months of AI with O3-FA supplementation)
timeFrame: At 6 months after start of AI therapy
measure: Change in percentage of total fatty acids for each PUFA group from baseline to 3 months of AI therapy alone
timeFrame: At 3 months after start of AI therapy
measure: Number of participants who develop AI-associated musculoskeletal symptoms (AIMSS)
timeFrame: Up to 9 months after start of AI therapy
measure: Number of participants that discontinue AI therapy due to AIMSS
timeFrame: Up to 9 months after start of AI therapy
measure: Number of participants that discontinue AI therapy due to toxicity.
timeFrame: Up to 9 months after start of AI therapy
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Lynn Henry, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wolfe F, Michaud K, Strand V. Expanding the definition of clinical differences: from minimally clinically important differences to really important differences. Analyses in 8931 patients with rheumatoid arthritis. J Rheumatol. 2005 Apr;32(4):583-9.
citation: Farrar JT, Pritchett YL, Robinson M, Prakash A, Chappell A. The clinical importance of changes in the 0 to 10 numeric rating scale for worst, least, and average pain intensity: analyses of data from clinical trials of duloxetine in pain disorders. J Pain. 2010 Feb;11(2):109-18. doi: 10.1016/j.jpain.2009.06.007. Epub 2009 Aug 8.