Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01849250
First received: May 6, 2013
Last updated: October 16, 2014
Last verified: August 2014

May 6, 2013
October 16, 2014
May 2013
February 2016   (final data collection date for primary outcome measure)
Percent change in normal breast tissue TNF-alpha levels [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
Two-sided student t-test or the nonparametric Wilcoxon rank-sum test will be used where appropriate.
Percent change in TNF-α levels [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
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.
Complete list of historical versions of study NCT01849250 on ClinicalTrials.gov Archive Site
  • Percent change in the breast tissue mRNA levels of tissue biomarkers [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    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.
  • Change in the presence of CLS-B measured by immunohistochemical techniques for CD68 [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Fisher's exact test will be used.
  • Change in CLS-B index measured by immunohistochemical techniques for CD68 [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Fisher's exact test will be used.
  • RBC fatty acid level as a surrogate of compliance [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
  • Percent change post minus pre treatment in the mRNA levels of tissue biomarkers (COX-2/IL-1β/aromatase) [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Fisher's exact test will be used.
  • RBC fatty acid level as a surrogate of compliance [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors
A Multicenter Phase II Study of Docosahexaenoic Acid (DHA) in Patients With a History of Breast Cancer, Premalignant Lesions, or Benign Breast Disease

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.

PRIMARY OBJECTIVES:

I. To determine whether treatment with docosahexaenoic acid (DHA) for 12 weeks (+ 2 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 1000mg 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]).

II. Evaluate age as a predictor of CLS-B and inflammatory biomarkers (tumor necrosis factor (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.

ARM II: Patients receive placebo PO BID for 12 weeks.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • Ductal Breast Carcinoma in Situ
  • Lobular Breast Carcinoma in Situ
  • Paget Disease of the Breast
  • Stage IA Breast Cancer
  • Stage IB Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Drug: docosahexaenoic acid
    Given PO
  • Other: placebo
    Given PO
    Other Name: PLCB
  • Other: laboratory biomarker analysis
    Correlative studies
  • Experimental: Arm I (docosahexaenoic acid)
    Patients receive docosahexaenoic acid PO BID for 12 weeks.
    Interventions:
    • Drug: docosahexaenoic acid
    • Other: laboratory biomarker analysis
  • Placebo Comparator: Arm II (placebo)
    Patients receive placebo PO BID for 12 weeks.
    Interventions:
    • Other: placebo
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
76
Not Provided
February 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Participants must have a history of histologically-confirmed stage I-III invasive breast cancer or ductal carcinoma in situ (DCIS), Paget's disease, lobular carcinoma in situ (LCIS), or proliferative benign breast disease
  • No evidence of disease (in situ or invasive cancer that would normally be treated by resection) at trial entry as determined by the investigator
  • >= 6 months from all previous breast cancer treatment (including surgery for invasive cancer, chest wall radiotherapy and chemotherapy, trastuzumab and endocrine therapy)
  • Participants must have a body mass index (BMI) >= 25, defined as (weight in kilograms/[height in meters]^2)
  • Participants must have adequate accessible breast tissue as determined by the treating physician, consisting of one breast unaffected by invasive cancer, which has not been radiated; a history of prior pre-invasive breast cancer or benign biopsy of this breast will be permitted
  • Daily DHA consumption =< 200 mg/day in the month prior to screening estimated by an abbreviated DHA food frequency questionnaire
  • Mammogram within no more than 6 months prior to the date of informed consent (normal/benign Breast Imaging-Reporting and Data System [bi-rads] 1 or 2) and no further routine breast imaging planned during the course of the study (12 weeks DHA/placebo)
  • Eastern Cooperative Oncology Group (ECOG) performance status must be =< 2 (Karnofsky >= 60%)
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 75,000/uL
  • White blood cells >= 3,000/uL
  • Hemoglobin >= 10 g/dL
  • Total bilirubin within 1.5 times the institution's upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) within 1.5 times the institution's ULN
  • Serum creatinine within 1.5 times the institution's ULN
  • Pregnant women will be excluded; for women of childbearing potential; negative pregnancy testing within 72 hours prior to or on study visit #1 (day 0) and willingness to use adequate contraception during the study intervention OR post-menopausal defined as any one of the following 1) prior hysterectomy, 2) absence of menstrual period for 1 year in the absence of prior chemotherapy or 3) absence of menstrual period for 2 years in women with a prior history of chemotherapy exposure who were pre-menopausal prior to chemotherapy
  • Willingness to comply with all study interventions and follow-up procedures including the ability to swallow the study drug
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Any type of active invasive cancer (excluding breast and non-melanoma skin cancer) within the preceding 18 months
  • A history of histologically-confirmed bilateral invasive breast cancer
  • Bilateral mastectomy
  • Prior history or evidence of metastatic breast cancer
  • Prior radiation therapy to the contralateral (unaffected) breast
  • Prior history of contralateral (unaffected) breast augmentation with breast implant placement
  • History of daily use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) in the month preceding study entry
  • History of DHA supplementation > 200 mg/day in the month preceding study entry
  • History of autoimmune disorder or any illness that requires therapy with chronic steroids or immunomodulators
  • History of therapeutic doses of anticoagulants including warfarin and low molecular weight heparin (e.g. for prior deep venous thrombosis and pulmonary embolism) in the preceding year
  • Participants may not be receiving any other investigational agents during the study
  • Women who have received cancer surgery, chemotherapy, biological therapy (e.g., trastuzumab), or radiotherapy for the treatment of any cancer within 6 months of study participation
  • Women who are receiving endocrine therapy for breast cancer treatment or chemoprevention including tamoxifen, letrozole, anastrozole, fulvestrant, or exemestane at the time of screening
  • Individuals with severe underlying chronic illness, such as uncontrolled diabetes; ongoing or active infection, psychiatric illness or social situations which in the opinion of the investigator would interfere with study participation
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to DHA or corn/soy oil in placebo agent
  • Pregnant, breastfeeding, or women of childbearing potential unwilling to use a reliable contraceptive method
Female
18 Years and older
No
United States
 
NCT01849250
NCI-2013-00859, NCI-2013-00859, 12-474, MDA10-16-01, 12-267, AAAK6752, MSKCC-12-267, H-33017, 2011-0766, MDA10-16-01, N01CN35159, P30CA016672
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Powell Brown M.D. Anderson Cancer Center
National Cancer Institute (NCI)
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP