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


Phase 2
18 Years
N/A
Open (Enrolling)
Female
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

Thank you

Trial Information

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


PRIMARY OBJECTIVES:

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).

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
(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
OR

- 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
placement

- 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:

Interventional

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:

No

Principal Investigator

Powel Brown

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2013-00859

NCT ID:

NCT01849250

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

Name

Location

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