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Altering Lipids for Tolerance of Aromatase Inhibitor Therapy (ALTA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04268134
Recruitment Status : Recruiting
First Posted : February 13, 2020
Last Update Posted : July 30, 2020
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Dietary Supplement: Omega-3 fatty acid supplement Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Omega-3 Fatty Acids, Oxylipins, and Tolerance of Aromatase Inhibitor Therapy
Actual Study Start Date : July 28, 2020
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : May 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Omega 3 fatty acid supplement
Omega-3 ethyl esters orally daily (containing 465 mg eicosapentaenoic acid [EPA] and 375 mg docosahexaenoic acid [DHA] per capsule,supplied as 4 x 1gm capsule)
Dietary Supplement: Omega-3 fatty acid supplement
4 capsules taken by mouth each day for 24 weeks (starting at the week 12 visit).
Other Name: Lovaza




Primary Outcome Measures :
  1. 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 [ Time Frame: From start of Omega-3 Fatty Acid (O3-FA) supplementation to 3 months of O3-FA (at 6 months after start of AI therapy) ]
    Plasma oxylipins from blood samples collected at the start of O3-FA supplementation (3 months after start of Aromatase Inhibitor [AI] therapy alone) and after 3 months of AI therapy + O3-FA supplementation (6 months after start of AI therapy alone) will be quantified using solid phase extraction-liquid chromatography-electrospray ionization tandem mass spectroscopy. Oxylipins will be grouped according to PUFA substrate (linoleic acid [LA], arachidonic acid [AA], alpha-linoleic acid [ALA], eicosapentaenoid acid [EPA], and docosahexaenoic acid [DHA]). For each patient, the percentage of total fatty acids of each PUFA group will be calculated at both time points. The overall study percentage per PUFA group will be derived from the mean percentage of that PUFA group for all patients at each time point. The change in percentage between the two time points will be reported in tabular format for each PUFA group.


Secondary Outcome Measures :
  1. 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) [ Time Frame: At 6 months after start of AI therapy ]
    Plasma oxylipins from blood samples collected at baseline (before AI therapy) and at 3 months of AI therapy + O3-FA supplementation (O3-FA supplementation starts 3 months after start of AI therapy) will be quantified using solid phase extraction-liquid chromatography-electrospray ionization tandem mass spectroscopy. Oxylipins will be grouped according to PUFA substrate (LA, AA, ALA, EPA and DHA). For each patient, the percentage of total fatty acids of each PUFA group will be calculated at both time points. The overall study percentage per PUFA group will be derived from the mean percentage of that PUFA group for all patients at each time point. The change in percentage between the two time points will be reported in tabular format for each PUFA group.

  2. Change in percentage of total fatty acids for each PUFA group from baseline to 3 months of AI therapy alone [ Time Frame: At 3 months after start of AI therapy ]
    Plasma oxylipins from blood samples collected at baseline and at 3 months after start of AI therapy alone will be quantified using solid phase extraction-liquid chromatography-electrospray ionization tandem mass spectroscopy. Oxylipins will be grouped according to PUFA substrate (LA, AA, ALA, EPA and DHA). For each patient, the percentage of total fatty acids of each PUFA group will be calculated at both time points. The overall study percentage per PUFA group will be derived from the mean percentage of that PUFA group for all patients at each time point. The change in percentage between the two time points will be reported in tabular format for each PUFA group.

  3. Number of participants who develop AI-associated musculoskeletal symptoms (AIMSS) [ Time Frame: Up to 9 months after start of AI therapy ]
    Patients will be considered to have developed AIMSS if any of the following apply: (1) a ≥0.22 increase in the Health Assessment Questionnaire (HAQ) score within 9 months, (2) a ≥2.0 increase in Brief Pain Inventory (BPI) average pain within 9 months, or (3) discontinuation of AI therapy within 9 months because of new or worsened musculoskeletal symptoms, assessed using a protocol-specific discontinuation form completed by the patient's provider. The HAQ assesses interference of pain with daily activities (range 0-3), with change of 0.22 defined as a clinically meaningful difference, as noted in the literature.* The BPI assesses average pain over 7 days (range 0-10), with a change of 2.0 defined as a clinically meaningful difference, as noted in the literature.* Patients whose providers specify pain as the first or second-ranked reason for discontinuation will be considered to have discontinued AI therapy because of new or worsened musculoskeletal symptoms. *See references.

  4. Number of participants that discontinue AI therapy due to AIMSS [ Time Frame: Up to 9 months after start of AI therapy ]
    Patients whose providers specify pain as the first or second-ranked reason for discontinuation (in a protocol-specific discontinuation form) will be considered to have discontinued AI therapy because of new or worsened musculoskeletal symptoms.

  5. Number of participants that discontinue AI therapy due to toxicity. [ Time Frame: Up to 9 months after start of AI therapy ]
    Patients whose providers specify toxicity as the first or second-ranked reason for discontinuation (in a protocol-specific discontinuation form) will be considered to have discontinued AI therapy due to toxicity.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  • 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).
  • Completion of chemotherapy, if indicated. Concurrent use of radiation therapy, LHRHa therapy, anti-HER2 therapy, 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04268134


Locations
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United States, Michigan
University of Michigan Rogel Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Cancer AnswerLine    800-865-1125    CancerAnswerLine@med.umich.edu   
Principal Investigator: N. Lynn Henry, MD, PhD         
Sponsors and Collaborators
University of Michigan Rogel Cancer Center
Investigators
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Principal Investigator: Lynn Henry, MD, PhD University of Michigan Rogel Cancer Center
Publications:
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Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT04268134    
Other Study ID Numbers: UMCC 2019.125
HUM00171150 ( Other Identifier: University of Michigan )
First Posted: February 13, 2020    Key Record Dates
Last Update Posted: July 30, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Michigan Rogel Cancer Center:
Aromatase inhibitor
Omega-3 fatty acid