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A Multicenter Phase II Study of Docosahexaenoic Acid (DHA) in Triple Negative Breast Cancer Survivors

Phase 2
18 Years
Open (Enrolling)
Estrogen Receptor-negative Breast Cancer, HER2-negative Breast Cancer, Progesterone Receptor-negative Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Triple-negative Breast Cancer

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Trial Information

A Multicenter Phase II Study of Docosahexaenoic Acid (DHA) in Triple Negative Breast Cancer Survivors


I. To determine whether treatment with docosahexaenoic acid (DHA) for 24 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 triple negative
breast cancer (TNBC).


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

- 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
(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 24 weeks.

ARM II: Patients receive placebo PO BID for 24 weeks.

Inclusion Criteria:

- Participants must have a history of histologically-confirmed breast cancer that meets
the following criteria

- Stage I, II, or III according to the American Joint Committee on Cancer (AJCC)
(7th edition)

- "Triple negative" disease defined here as invasive carcinoma that does not
express the estrogen receptor (ER), progesterone receptor (PR) or human
epidermal growth factor receptor 2 (HER2) as follows:

- For ER and PR =< 10% by immunohistochemistry (IHC) AND no current or
planned hormone therapy.

- For HER2 any one of the following four options must apply

- Criteria for defining HER2 negativity:

- IHC: 0-1; fluorescence in situ hybridization (FISH) not
performed; no adjuvant trastuzumab; patient eligible OR

- IHC: 0-1; FISH =< 2.0 ; no adjuvant trastuzumab; patient eligible

- IHC not performed; FISH =< 2.0 ; no adjuvant trastuzumab; patient
eligible OR

- IHC 2; FISH =< 2.0 ; no adjuvant trastuzumab; patient eligible

- No evidence of disease 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)

- 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 the last 6 months (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 (6 months 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

- The effects of DHA on the developing human fetus at the recommended therapeutic dose
are unknown; therefore, 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

- Known deleterious breast cancer (BRCA) 1/2 mutation carriers; of note BRCA mutation
testing is not a requirement for study entry; women with BRCA mutations of unknown
significance will be eligible

- History of daily use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) in
the month preceding study entry

- History of chronic statin use, defined as any prescription in the preceding year

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Outcome Measure:

Percent change in normal breast tissue TNF-alpha levels

Outcome Description:

Student t-test or the nonparametric Wilcoxon rank-sum test will be used.

Outcome Time Frame:

Baseline to 24 weeks

Safety Issue:


Principal Investigator

Powel Brown

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

May 2013

Completion Date:

Related Keywords:

  • Estrogen Receptor-negative Breast Cancer
  • HER2-negative Breast Cancer
  • Progesterone Receptor-negative Breast Cancer
  • Stage IA Breast Cancer
  • Stage IB Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Triple-negative Breast Cancer
  • Breast Neoplasms



Baylor College of MedicineHouston, Texas  77030
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
M D Anderson Cancer CenterHouston, Texas  77030
Columbia University Medical CenterNew York, New York  10032