Benign Breast NeoplasmPhase 2NCT01849250
Study of Docosahexaenoic Acid (DHA) in Triple Negative Breast Cancer Survivors
A Phase 2 study testing Docosahexaenoic Acid in people with Benign Breast Neoplasm and Ductal Breast Carcinoma In Situ, run by National Cancer Institute (NCI) at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Benign Breast Neoplasm, Ductal Breast Carcinoma In Situ, Invasive Breast Carcinoma
- What is being tested?
- Docosahexaenoic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 4 sitesUnited States
- Study dates
- May 2013to 22 Apr 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
MD Anderson Cancer Center
Houston, Texas, 77030
Columbia University/Herbert Irving Cancer Center
New York, New York, 10032
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- 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
- Being tested
- Docosahexaenoic Acid, Placebo
- Medical subject headings
- Carcinoma, Intraductal, Noninfiltrating, Breast Carcinoma In Situ, Paget's Disease, Mammary, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Docosahexaenoic AcidDrug
Also called Fatty Acid 22:6
Given PO
PlaceboOther
Also called placebo therapy, PLCB, sham therapy
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (Docosahexaenoic Acid) | Experimental | Docosahexaenoic Acid orally twice a day (PO BID) for 12 weeks. Receives: Drug: Docosahexaenoic Acid |
| Arm II (placebo) | Placebo comparator | Placebo orally twice a day (PO BID) for 12 weeks. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 12 weeks
Secondary outcomes (6)
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.
Measured: Baseline to 12 weeks
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).
Measured: Baseline to 12 weeks
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.
Measured: Baseline to 12 weeks
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.
Measured: Baseline to 12 weeks
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.
Measured: Baseline and 12 weeks
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.
Measured: Baseline and week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2013 (estimated)
- Study startMay 2013
- Primary completion11 Jan 2016
- Study completion22 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Benign Breast NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ayca Gucalp, Principal investigator, Memorial Sloan Kettering Cancer CenterPowel H. Brown, MD, Study chair, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01849250
- Sponsor's protocol ID
- NCI-2013-00859
- Other IDs
- NCI-2013-00859, 12-474, 12-267, N01-CN-2012-00034, DFCI:12- 474, AAAK6752, MSKCC-12-267, H-33017
- Status last verified
- Dec 2021
- First submitted
- 6 May 2013
- Last updated
- 28 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01849250
- Acronym / sponsor ID
- NCI-2013-00859
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- May 2013 (actual)
- Primary completion
- 11 Jan 2016 (actual)
- Study completion
- 22 Apr 2020 (actual)
- First posted
- 8 May 2013 (estimated)
- Results
- Posted 28 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (Docosahexaenoic Acid) | Experimental | Drug: Docosahexaenoic AcidDocosahexaenoic Acid orally twice a day (PO BID) for 12 weeks. |
| Arm II (placebo) | Placebo comparator | Other: PlaceboPlacebo orally twice a day (PO BID) for 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Docosahexaenoic AcidAlso: Fatty Acid 22:6Given PO | Drug | Arm I (Docosahexaenoic Acid) |
| PlaceboAlso: placebo therapy, PLCB, sham therapyGiven PO | Other | Arm II (placebo) |
Primary outcome
Normal Breast Tissue Expression of Tumor Necrosis Factor Alpha (TNF-alpha) Levels
Time frame: Baseline to 12 weeks
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.
6 secondary outcomes
Number of Participants With Crown-like Structures of the Breast (CLS-B) at Baseline and Post-treatment
Time frame: Baseline to 12 weeks
Absolute Change in CLS-B/cm^2 Adjusted for the Pre-treatment Measurements
Time frame: Baseline to 12 weeks
Breast Tissue Cox 2 mRNA Levels at Baseline and 12 Weeks
Time frame: Baseline to 12 weeks
Mean Difference in the Breast Tissue IL- Beta mRNA Levels of Tissue Biomarkers
Time frame: Baseline to 12 weeks
Mean Difference in the Breast Tissue Aromatase mRNA Levels of Tissue Biomarkers
Time frame: Baseline and 12 weeks
Red Blood Cell (RBC) Fatty Acid Level as a Surrogate of Compliance
Time frame: Baseline and week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ayca Gucalp principal investigator
Memorial Sloan Kettering Cancer Center
Powel H. Brown, MD study chair
M.D. Anderson Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Docosahexaenoic Acid in people with Benign Breast Neoplasm and Ductal Breast Carcinoma In Situ, run by National Cancer Institute (NCI) at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Normal Breast Tissue Expression of Tumor Necrosis Factor Alpha (TNF-alpha) Levels (time frame: Baseline to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2021.