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Study of Docosahexaenoic Acid (DHA) in Triple Negative Breast Cancer Survivors

Primary Purpose

Benign Breast Neoplasm, Ductal Breast Carcinoma In Situ, Invasive Breast Carcinoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Docosahexaenoic Acid
Placebo
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Benign Breast Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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, 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 week 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

Sites / Locations

  • Dana-Farber Cancer Institute
  • Columbia University/Herbert Irving Cancer Center
  • Memorial Sloan-Kettering Cancer Center
  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (Docosahexaenoic Acid)

Arm II (placebo)

Arm Description

Docosahexaenoic Acid orally twice a day (PO BID) for 12 weeks.

Placebo orally twice a day (PO BID) for 12 weeks.

Outcomes

Primary Outcome Measures

Normal Breast Tissue Expression of Tumor Necrosis Factor Alpha (TNF-alpha) Levels
Differences in normal breast tissue levels of TNF-α 12 weeks post-treatment relative to pre-treatment for active treatment and placebo arm, compared using analysis of covariance where the post-treatment measurements were used as a dependent variable and the pretreatment measurements were included as a covariate in the analysis. For the primary study end-point TNF-α levels will be measured by quantitative real-time PCR (mRNA essays) on extracted RNA from breast core biopsies. Relative expression determined using the Computed Tomography (ΔΔCT) analysis protocol.

Secondary Outcome Measures

Number of Participants With Crown-like Structures of the Breast (CLS-B) at Baseline and Post-treatment
An indicator of whether a subject is detected with CLS-B or not.
Absolute Change in CLS-B/cm^2 Adjusted for the Pre-treatment Measurements
To assess the severity of CLS-B using the following formula: number of CLS-B/cm^2. The absolute change in the CLS-B/cm^2 calculated according to the formula; Change in CLS-B/cm^2 = (post-treatment CLS-B/cm^2) - (pre-treatment CLS-B/cm^2).
Breast Tissue Cox 2 mRNA Levels at Baseline and 12 Weeks
Biomarkers COX-2 are measured by quantitative real-time PCR. Differences between active treatment and placebo arm for each biomarker will be compared using analysis of covariance where the post treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis.
Mean Difference in the Breast Tissue IL- Beta mRNA Levels of Tissue Biomarkers
Biomarkers IL-1Beta are measured by quantitative real-time PCR. Differences between active treatment and placebo arm for each biomarker will be compared using analysis of covariance where the post treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis.
Mean Difference in the Breast Tissue Aromatase mRNA Levels of Tissue Biomarkers
Biomarkers Aromatase are measured by quantitative real-time PCR. Differences between active treatment and placebo arm for each biomarker will be compared using analysis of covariance where the post treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis.
Red Blood Cell (RBC) Fatty Acid Level as a Surrogate of Compliance
Whole blood samples collected for red blood cell fatty acid analyses at baseline and week 12 (+ 2 weeks). RBC fatty acid composition analyzed by gas chromatography (GC) with flame ionization detection.

Full Information

First Posted
May 6, 2013
Last Updated
December 3, 2021
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01849250
Brief Title
Study of Docosahexaenoic Acid (DHA) in Triple Negative Breast Cancer Survivors
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
May 2013 (Actual)
Primary Completion Date
January 11, 2016 (Actual)
Study Completion Date
April 22, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
PRIMARY OBJECTIVES: I. To determine whether treatment with docosahexaenoic acid (DHA) for 12 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 1000 mg 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]). Change from baseline in CLS-B/cm^2 defined as the number of CLS-B/cm^2. 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 12 weeks. ARM II: Patients receive placebo PO BID for 12 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Benign Breast Neoplasm, Ductal Breast Carcinoma In Situ, Invasive Breast Carcinoma, Lobular Breast Carcinoma In Situ, Paget Disease of the Breast, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
65 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (Docosahexaenoic Acid)
Arm Type
Experimental
Arm Description
Docosahexaenoic Acid orally twice a day (PO BID) for 12 weeks.
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Placebo orally twice a day (PO BID) for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Docosahexaenoic Acid
Other Intervention Name(s)
Fatty Acid 22:6
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo therapy, PLCB, sham therapy
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Normal Breast Tissue Expression of Tumor Necrosis Factor Alpha (TNF-alpha) Levels
Description
Differences in normal breast tissue levels of TNF-α 12 weeks post-treatment relative to pre-treatment for active treatment and placebo arm, compared using analysis of covariance where the post-treatment measurements were used as a dependent variable and the pretreatment measurements were included as a covariate in the analysis. For the primary study end-point TNF-α levels will be measured by quantitative real-time PCR (mRNA essays) on extracted RNA from breast core biopsies. Relative expression determined using the Computed Tomography (ΔΔCT) analysis protocol.
Time Frame
Baseline to 12 weeks
Secondary Outcome Measure Information:
Title
Number of Participants With Crown-like Structures of the Breast (CLS-B) at Baseline and Post-treatment
Description
An indicator of whether a subject is detected with CLS-B or not.
Time Frame
Baseline to 12 weeks
Title
Absolute Change in CLS-B/cm^2 Adjusted for the Pre-treatment Measurements
Description
To assess the severity of CLS-B using the following formula: number of CLS-B/cm^2. The absolute change in the CLS-B/cm^2 calculated according to the formula; Change in CLS-B/cm^2 = (post-treatment CLS-B/cm^2) - (pre-treatment CLS-B/cm^2).
Time Frame
Baseline to 12 weeks
Title
Breast Tissue Cox 2 mRNA Levels at Baseline and 12 Weeks
Description
Biomarkers COX-2 are measured by quantitative real-time PCR. Differences between active treatment and placebo arm for each biomarker will be compared using analysis of covariance where the post treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis.
Time Frame
Baseline to 12 weeks
Title
Mean Difference in the Breast Tissue IL- Beta mRNA Levels of Tissue Biomarkers
Description
Biomarkers IL-1Beta are measured by quantitative real-time PCR. Differences between active treatment and placebo arm for each biomarker will be compared using analysis of covariance where the post treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis.
Time Frame
Baseline to 12 weeks
Title
Mean Difference in the Breast Tissue Aromatase mRNA Levels of Tissue Biomarkers
Description
Biomarkers Aromatase are measured by quantitative real-time PCR. Differences between active treatment and placebo arm for each biomarker will be compared using analysis of covariance where the post treatment measurements will be used as a dependent variable and the pretreatment measurements will be included as a covariate in the analysis.
Time Frame
Baseline and 12 weeks
Title
Red Blood Cell (RBC) Fatty Acid Level as a Surrogate of Compliance
Description
Whole blood samples collected for red blood cell fatty acid analyses at baseline and week 12 (+ 2 weeks). RBC fatty acid composition analyzed by gas chromatography (GC) with flame ionization detection.
Time Frame
Baseline and week 12

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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, 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 week 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ayca Gucalp
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Powel H. Brown, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Columbia University/Herbert Irving Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Study of Docosahexaenoic Acid (DHA) in Triple Negative Breast Cancer Survivors

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