Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 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: June 30, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
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
Other: placebo
Other: laboratory biomarker analysis
Phase 2

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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 76
Study Start Date: May 2013
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (docosahexaenoic acid)
Patients receive docosahexaenoic acid PO BID for 12 weeks.
Drug: docosahexaenoic acid
Given PO
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO BID for 12 weeks.
Other: placebo
Given PO
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01849250

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Judy E. Garber    617-632-5770    judy_garber@dfci.harvard.edu   
Principal Investigator: Judy E. Garber         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Katherine D. Crew    212-305-1732    kd59@columbia.edu   
Principal Investigator: Katherine D. Crew         
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Clifford A. Hudis    646-888-4551    hudisc@mskcc.org   
Principal Investigator: Clifford A. Hudis         
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Julie R. Nangia    713-798-8421    nangia@bcm.edu   
Principal Investigator: Julie R. Nangia         
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Powel H. Brown    713-792-4509    phbrown@mdanderson.org   
Principal Investigator: Powel H. Brown         
Sponsors and Collaborators
Investigators
Principal Investigator: Powell Brown M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01849250     History of Changes
Other Study ID Numbers: NCI-2013-00859, NCI-2013-00859, 12-474, MDA10-16-01, 12-267, AAAK6752, MSKCC-12-267, H-33017, 2011-0766, MDA10-16-01, P30CA016672, N01CN35159
Study First Received: May 6, 2013
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Carcinoma
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Carcinoma, Ductal, Breast
Paget's Disease, Mammary
Carcinoma, Lobular
Neoplasms by Site
Neoplasms
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Carcinoma, Ductal

ClinicalTrials.gov processed this record on August 28, 2014