A Multicenter Phase II Study of Docosahexaenoic Acid (DHA) in Patients with a History of Breast Cancer, Premalignant Lesions, Benign Breast Disease.
Docosahexaenoic Acid (DHA) (trade name is DHASCO® Oil)
Powel H. Brown
The goal of this clinical research study is to learn if Docosahexaenoic Acid (DHA) can help to reduce the amount of inflammation in the breasts. DHA is an omega-3 fatty acid that is normally present in the human body from the foods that you eat. Fatty fish and organ meats are the main sources of DHA, with smaller amounts coming from shellfish, eggs, and poultry. Diets rich in fish oil have been associated with a decreased risk of a number of cancers, including breast cancer. Previous studies have shown breast inflammation can increase the risk of breast cancer. The severity of breast inflammation correlates to a woman’s body mass index (a calculation based on an individual’s height and weight). Therefore, this study is being conducted only in women with a body mass index greater than or equal to 25%. We will also be studying the effect of DHA on levels of several different substances, called biomarkers, in your blood and breast tissue. These biomarkers may be used to track the amount of breast inflammation and the risk of developing breast cancer. This is a randomized study. You will be randomly assigned to get a dose of DHA or placebo. A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect. Neither you or your doctor will know whether you are getting DHA or placebo.
Disease Group: Breast
Treatment Agent: Docosahexaenoic Acid (DHA) (trade name is DHASCO® Oil)
Treatment Location: Both at MDACC & and Other Sites
Sponsor: NCI/Division of Cancer Prevention
Primary Objectives: 1. To determine whether treatment with docosahexaenoic acid (DHA) for 12(+2 weeks) weeks at 1000mg twice daily as compared to placebo reduces normal breast tissue levels of TNF-a in overweight and obese patients with a history of 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. Secondary Objectives: 1. To investigate the effect of DHA at 1000mg twice daily on tissue biomarkers We will determine the change from the baseline in: COX-2/IL-1beta/aromatase measured by quantitative real-time PCR. Crown-like Structures of the breast (CLS-B) measured by immunohistochemical techniques for CD68. Total number of CLS-B/slide will be recorded. CLS-B index determined as follows: [(number of slides with evidence of at least one CLS-B) / (total number of slides examined)]. CLS-B/cm2 defined as the number of CLS-B/cm2 Gene expression by RNA-seq 2. Evaluate age as a predictor of CLS-B and inflammatory biomarkers (TNF-a/COX-2/IL-1beta at baseline and over the time of treatment. 3. Evaluate RBC fatty acid level as a surrogate of compliance.
IRB Review and Approval Date: 05/01/2013
Recruitment Status: Closed
Projected Accrual: 35
1) Participants must be female greater than or equal to18 years of age,
irrespective of menopausal status. The minimum age of 18 was chosen as
breast cancer is extremely rare in women less than 18 years.
2) 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.
3) No evidence of disease (in situ or invasive cancer that would normally be treated by resection ) at trial entry as determined by the investigator.
4) Greater than or equal 6 months from all previous breast cancer treatment (including surgery for invasive cancer, chest wall radiotherapy and chemotherapy).
5) Participants must have a body mass index (BMI) greater than or equal to 25, defined as [Weight in Kilograms/(Height in Meters)2].
6) 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.
7) Daily DHA consumption less than or equal to 200 mg/day in the month prior to screening estimated by an abbreviated DHA food frequency questionnaire.
8) Mammogram within no more than 6 months prior to the date of the informed consent (normal/benign bi-rads 1 or 2) and no further routine breast imaging planned during the course of the study (6 months DHA/placebo).
9) ECOG performance status must be less than or equal to (Karnofsky greater than or equal to 60%).
10) Participants must have normal organ and marrow function defined as ALL of the below: a) Absolute neutrophil count greater than or equal to1,500/microL b) Platelets greater than or equal 75,000/microL c) White Blood Cells greater than or equal to 3,000/microL d)Hemoglobin greater than or equal to 10 g/dL e) Total bilirubin within 1.5 times the institution’s ULN f)AST (SGOT)/ALT (SGPT) within 1.5 times the institution’s ULN g) Serum creatinine within 1.5 times the institution’s ULN (ULN = upper limit of normal as defined by the participating institutions laboratory. It is not a requirement of the study to have these results tested at the central site (MSKCC)).
11) 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.
12) Willingness to comply with all study interventions and follow-up procedures including the ability to swallow the study drug.
13) Ability to understand and the willingness to sign a written informed consent document
1) Any type of active invasive cancer (excluding breast and non-melanoma
skin cancer) within the preceding 18 months
2) A history of histologically-confirmed bilateral invasive breast cancer.
3) Bilateral mastectomy.
4) Prior history or evidence of metastatic breast cancer
5) Prior radiation therapy to the contralateral (unaffected) breast
6) Prior history of contralateral (unaffected) breast augmentation with breast implant placement.
7) Known deleterious 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
8) History of daily use of aspirin or NSAIDs in the week preceding study entry.
9) History of DHA supplementation > 200 mg/day in the month preceding study entry.
10) History of autoimmune disorder or any illness that requires therapy with chronic steroids or immunomodulators.
11) 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.
12) Participants may not be receiving any other investigational agents during the study.
13) 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
14) Women who are receiving endocrine therapy for breast cancer treatment or chemoprevention including tamoxifen, letrozole, anastrozole, fulvestrant, or exemestane at the time of screening
15) 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.
16) History of allergic reactions attributed to compounds of similar chemical or biologic composition to DHA or corn/soy oil in placebo agent.
17) Pregnant, breastfeeding, or women of childbearing potential unwilling to use a reliable contraceptive method.
Information and next steps
Powel H. Brown
Clinical Cancer Prevention
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