Clinical Trial: Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Multicenter Phase II Study of Docosahexaenoic Acid (DHA) in Patients With a History of Breast Cancer, Premalignant Lesions, or Benign Breast Disease

Brief Summary: This randomized phase II trial studies how well docosahexaenoic acid works in preventing recurrence in breast cancer survivors. Docosahexaenoic acid supplement may prevent recurrence in breast cancer survivors.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine whether treatment with docosahexaenoic acid (DHA) for 12 weeks at 1000 mg twice daily as compared to placebo reduces normal breast tissue levels of tumor necrosis factor-alpha (TNF-alpha) in overweight and obese patients with a history of stage I-III invasive breast cancer, ductal carcinoma in situ (DCIS), Paget's disease, lobular carcinoma in situ (LCIS), or proliferative benign breast disease.

SECONDARY OBJECTIVES:

I. To investigate the effect of DHA at 1000 mg twice daily on tissue biomarkers

  • Change from the baseline in cyclooxygenase-2 (COX-2)/interleukin-1-beta (IL-1beta)/aromatase measured by quantitative real-time polymerase chain reaction (PCR).
  • Change from the baseline in crown-like structures of the breast (CLS-B) measured by immunohistochemical techniques for cluster of differentiation (CD)68.
  • Change from baseline in CLS-B index determined as follows: ([number of slides with evidence of at least one CLS-B]/[total number of slides examined]).
  • Change from baseline in CLS-B/cm^2 defined as the number of CLS-B/cm^2. II. Evaluate age as a predictor of CLS-B and inflammatory biomarkers (TNF-alpha/COX-2/IL-1beta) at baseline and over the time of treatment.

III. Evaluate red blood cell (RBC) fatty acid level as a surrogate of compliance.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive docosahexaenoic acid orally (PO) twice daily (BID) for 12 weeks.

Differences between active treatment and placebo arm will be compared using analysis of covariance where the post-treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis. Two-sided student t-test or the nonparametric Wilcoxon rank-sum test will be used where appropriate.



Original Primary Outcome: Percent change in TNF-α levels [ Time Frame: Baseline to 24 weeks ]

For the primary analysis the between treatment arm differences in the primary endpoint will be compared. Within each treatment arm, we will examine whether treatment by DHA/placebo results in any percent change in TNF-α levels that is significantly different than zero.


Current Secondary Outcome:

  • Absolute change in CLS-B index defined as follows (number of slides with at least one CLS-B)/(total number of slides examined) measured by immunohistochemical techniques for CD68 [ Time Frame: Baseline to 12 weeks ]
    Fisher's exact test will be used.
  • Absolute change in CLS-B/cm^2 adjusted for the pre-treatment measurements [ Time Frame: Baseline to 12 weeks ]
  • Absolute change in the presence of CLS-B measured by immunohistochemical techniques for CD68 [ Time Frame: Baseline to 12 weeks ]
    Fisher's exact test will be used.
  • Percent change in the breast tissue mRNA levels of tissue biomarkers [ Time Frame: Baseline to 12 weeks ]
    Biomarkers (COX-2/IL-1beta/aromatase) are measured by quantitative real-time PCR. Paired t-test or one-sample Wilcoxon rank-sum test will be used.
  • RBC fatty acid level as a surrogate of compliance [ Time Frame: Up to 12 weeks ]


Original Secondary Outcome:

  • Percent change post minus pre treatment in the mRNA levels of tissue biomarkers (COX-2/IL-1β/aromatase) [ Time Frame: Baseline to 24 weeks ]
    Student t-test or the nonparametric Wilcoxon rank-sum test will be used.
  • Absolute change in the presence of CLS-B [ Time Frame: Baseline to 24 weeks ]
    Data will be summarized using graphical tools and summary statistics in terms of mean +/- standard deviation and median (range) for continuous variables and count and frequencies for categorical variables. Post minus pre percent change or post minus pre absolute change between and within treatment arms will be compared. The association between post minus pre percent change or post minus pre absolute change of biomarker values and baseline values will be summarized using the Pearson or Spearman correlation coefficient.
  • Absolute change in CLS-B index [ Time Frame: Up to 24 weeks ]
    Fisher's exact test will be used.
  • RBC fatty acid level as a surrogate of compliance [ Time Frame: Baseline to 24 weeks ]


Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 6, 2013
Date Started: May 2013
Date Completion:
Last Updated: June 20, 2016
Last Verified: March 2016