Browse EPPT > MDA10-16-01
Randomized Multicenter Phase II Study of Docosahexaenoic Acid (DHA) in Patients with a History of Breast Cancer, Premalignant Lesions, or Benign Breast Disease

The following datasets contain the data available for EPPT MDA10-16-01. The description and documentation for each file is listed below. SAS7bdat and CSV versions of the actual data will be available to CDAS projects approved to use this study's data.

Analysis Datasets

Files	Description
Data Dictionary (PDF - 840.3 KB)	1. The Enhanced Person dataset contains all information relevant for most analyses. Each record represents one participant and contains updated variable names, formats, and labels. All information coming from non-person-based datasets has been converted into a person-based format.
Data Dictionary (PDF - 164.6 KB)	2. The Adverse Events dataset contains adverse event information, including onset date, grade of severity, attribution to the study agent, and outcome. This version of the dataset includes updated variable names, formats, and labels.
Data Dictionary (PDF - 162.0 KB)	3. The RNA dataset contains RNA Fragments Per Kilobase Million and raw count gene values at the start and end of the trial. This version of the datasets includes updated variable names, formats, and labels, as well as additional study identifiers.

Raw Datasets

These 44 datasets contain the raw form data received, excluding PII.

Show these datasets

Files	Description
Data Dictionary (PDF - 172.8 KB)	1. The adverseevents dataset contains adverse events that occurred during the study.
Data Dictionary (PDF - 165.8 KB)	2. The aeandconmedeval dataset contains yes/no variables for whether participants had any adverse events or used any concomitant medications since the last study visit.
Data Dictionary (PDF - 167.2 KB)	3. The agentinterruption dataset contains agent interruptions during the study due to adverse events, participant error, etc.
Data Dictionary (PDF - 162.6 KB)	4. The analysis_20160921_comorbidities dataset contains comorbidity information for Dyslipidemia, Diabetes Mellitus, and Hypertension.
Data Dictionary (PDF - 166.3 KB)	5. The baselinesymptoms dataset contains unusual symptoms participant experienced before starting the study.
Data Dictionary (PDF - 171.5 KB)	6. The bloodrbcfattyacidlevelsvisit1 dataset contains blood sample storage information at visit 1.
Data Dictionary (PDF - 169.9 KB)	7. The bloodrbcfattyacidlevelsvisit2 dataset contains blood sample storage information at visit 2.
Data Dictionary (PDF - 187.8 KB)	8. The breastcancerhistory dataset contains breast cancer history, including the site of the cancer, the severity of the cancer, and the current status of the breast cancer.
Data Dictionary (PDF - 168.7 KB)	9. The breasttissuehistologyvisit1 dataset contains tissue core biopsy 1 results from visit 2. Used to determine continued study eligibility.
Data Dictionary (PDF - 168.6 KB)	10. The breasttissuehistologyvisit2 dataset contains tissue core biopsy 1 results from visit 2. Used to determine continued study eligibility.
Data Dictionary (PDF - 170.6 KB)	11. The clinicallabdatabloodchemistry dataset contains results of blood tests and whether or not they were abnormal/out of range.
Data Dictionary (PDF - 169.4 KB)	12. The clinicallabdatahematology dataset contains results of hematology tests and whether or not they were abnormal/out of range.
Data Dictionary (PDF - 169.6 KB)	13. The clinicallabdataotherlabtests dataset contains results of other lab tests and whether or not they were abnormal/out of range.
Data Dictionary (PDF - 169.1 KB)	14. The cliniclabhematologydifferential dataset contains results of hematology tests and whether or not they were abnormal/out of range.
Data Dictionary (PDF - 174.2 KB)	15. The cls_data_6116 dataset contains cLs data pre/post study, indicating adipose area, fibrous area, etc.
Data Dictionary (PDF - 171.2 KB)	16. The compliance dataset contains study protocol compliance information.
Data Dictionary (PDF - 173.7 KB)	17. The compliancepre2015 dataset contains study protocol compliance information (pre-2015).
Data Dictionary (PDF - 173.7 KB)	18. The concomitantmedications dataset contains any concomitant medications taken throughout the study.
Data Dictionary (PDF - 234.5 KB)	19. The dat_lipidswide_20160831 dataset contains lipid test results. Indicates value pre-study agent, post-study agent, and the difference between the two.
Data Dictionary (PDF - 169.4 KB)	20. The dat_qpcrwide_20160809 dataset contains biomarker test results from Tissue Core Biopsies 3-6.
Data Dictionary (PDF - 191.9 KB)	21. The dhafoodfrequencyquestionnaire dataset contains answers submitted for each question on the food frequency questionnaire.
Data Dictionary (PDF - 165.5 KB)	22. The exclusioncriteria dataset contains whether or not the participant met any criteria that would exclude them from eligibility for the study.
Data Dictionary (PDF - 167.9 KB)	23. The exclusioncriteriapre2015 dataset contains whether or not the participant met any criteria that would exclude them from eligibility for the study (pre-2015).
Data Dictionary (PDF - 164.2 KB)	24. The fpkm_expr dataset contains RNA Fragments Per Kilobase Million gene values at the start and end of the trial.
Data Dictionary (PDF - 166.2 KB)	25. The inclusioncriteria dataset contains whether or not the participant met all inclusion criteria that would allow eligibility for the study.
Data Dictionary (PDF - 167.0 KB)	26. The inclusioncriteriapre2015 dataset contains whether or not the participant met all inclusion criteria that would allow eligibility for the study (pre-2015).
Data Dictionary (PDF - 165.5 KB)	27. The interventionadministrationblind dataset contains study agent provide/start date.
Data Dictionary (PDF - 166.5 KB)	28. The interventionadminpre2015 dataset contains study agent provide/start date (pre-2015).
Data Dictionary (PDF - 169.2 KB)	29. The medicalsurgicalhistory dataset contains medical/surgical history for each body system and whether or not the participant has any allergies.
Data Dictionary (PDF - 167.5 KB)	30. The medicalsurgicalhistothbodysystem dataset contains medical/surgical history for other body systems and whether or not the participant has any allergies.
Data Dictionary (PDF - 170.0 KB)	31. The offstudy dataset contains the reason each participant went off of the study.
Data Dictionary (PDF - 163.0 KB)	32. The patient_list_unblinded dataset contains unblinding information for the study.
Data Dictionary (PDF - 185.9 KB)	33. The physicalexam dataset contains general anthropometry information, including height, weight, pulse, blood pressure, etc.
Data Dictionary (PDF - 165.4 KB)	34. The previoustherapy dataset contains information on previous therapies, including radiation therapy, hormonal therapy, etc.
Data Dictionary (PDF - 168.3 KB)	35. The previoustherapydetails dataset contains information on previous therapies, including radiation therapy, hormonal therapy, etc.
Data Dictionary (PDF - 166.2 KB)	36. The randomization dataset contains study eligibility and randomization date.
Data Dictionary (PDF - 164.1 KB)	37. The raw_counts dataset contains RNA raw count gene values at the start and end of the trial.
Data Dictionary (PDF - 180.6 KB)	38. The registrationrace dataset contains general demographic information.
Data Dictionary (PDF - 167.0 KB)	39. The screening dataset contains screening information, such as how participant heard about the study and their biggest influence for registering.
Data Dictionary (PDF - 167.3 KB)	40. The telephonecontact dataset contains information on the last telephone contact with the participant as part of the study in order to determine if any possibly agent-related adverse events had resolved.
Data Dictionary (PDF - 169.4 KB)	41. The tissuecorebiopsy2 dataset contains information on tissue core sample 2. These cores were used to determine CLS-B/CLS-B index/CLS-B/cm2.
Data Dictionary (PDF - 172.4 KB)	42. The tissuecorebiopsy3thru6 dataset contains information on tissue core sample 3-6. These cores were used to determine primary study outcome results of TNFα /COX-2/IL1β /aromatase.
Data Dictionary (PDF - 172.1 KB)	43. The tissuecorebiopsy7 dataset contains information on tissue core sample 7. These cores were stored for later use.
Data Dictionary (PDF - 164.2 KB)	44. The verification dataset contains investigator verification information.

Trial Summary

This phase II double blinded trial is designed to determine whether treatment with DHA reduces levels of tumor necrosis factor-alpha (TNF) in normal breast tissue in overweight and obese female patients with a history of breast cancer or DCIS, LCIS, Pagets Disease or benign proliferative breast disease as its primary endpoint. Additionally, the study investigates the effect of DHA on various tissue biomarkers and evaluates red blood cell (RBC) fatty acid levels as a surrogate of compliance as secondary endpoints.

Randomized trial with two arms:

• Arm I: DHA (2 x 500mg capsules twice daily)
• Arm II: Matched Placebo (2 capsules twice daily)

Target Randomizable Enrollment: 64

Target Evaluable Enrollment: 50

Statistical Analysis:

This randomized phase II trial was designed to enroll a total of 64 subjects to ensure a targeted 50 evaluable subjects after accounting for an expected 10% dropout rate and around 10% nonevaluable rate. Subjects were randomized at 1:1 ratio to each study arm using urn randomization stratified by study site. The primary objective was to determine whether treatment with DHA compared with placebo reduced normal breast tissue levels of TNF in overweight and obese patients meeting the study inclusion criteria. Assuming an expected 0.4 correlation between pre- and posttreatment biomarker levels, the planned sample size has 80% power to detect effect size as small as 0.74 in the adjusted TNF levels between the two arms at a two-sided 0.05 significance level using ANCOVA (37). This sample size also had 80% power at 0.05 significance level for an effect size as small as 0.58 for the post- minus pretreatment percent change in the biomarker level in the treatment arm using a paired two-sided t test.

Enrollment Statistics

Actual Registration: 84 (82 to be outputed)

• 65 people randomized (65 of 84 registered)
  • 32 in Arm I: DHA (32 of 65 randomized)
    • 29 participants completed study and were evaluable for analysis (29 of 32)
    • 3 participants did not complete study (3 of 32)
      • 2 due to noncompliance
      • 1 due to pharmacy error
  • 33 in Arm II: Placebo (33 of 65 randomized)
    • 25 participants completed study and were evaluable for analysis (25 of 33)
    • 1 Ineligible after being randomized into Placebo group, but before intervention administration, due to elevated liver enzymes (1 of 33 randomized)
    • 7 participants did not complete study (7 of 33)
      • 3 due to noncompliance
      • 2 due to inability to confirm compliance
      • 1 due to adverse event
      • 1 due to pharmacy error
• 19 people not randomized (19 of 84 registered)
  • 8 due to ineligibility
  • 6 declined participation
  • 2 withdrew consent (1 of which was also ineligible)
  • 3 due to other reasons
    • 2 due to scheduling issues
    • 1 due to postmenopausal spotting

Total Study Population Demographics: (64 Randomized and Eligible People)

• Age (years):
  • Median: 59
  • IQR: 52 - 62
• BMI:
  • Median: 30.5
  • IQR: 27.5 - 33.9
• Menopausal: 54 (84%)
• Self-reported Race:
  • White: 55 (86%)
  • Black or African-American: 6 (10%)
  • Asian: 1 (2%)
  • Asian-White: 1 (2%)
  • Not Reported: 1 (2%)
• History of a benign lesion: 15 (23%)
• History of a premalignant lesion: 12 (19%)
• History of invasive breast cancer: 37 (58%)
• No statistically significant differences in clinicopathologic features noted between the evaluable and unevaluable cohorts.

Final Analysis Population: 54

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

The Schema is a timeline of the study. It indicates start/end points, visits expected, major testing to be done, and any other information that is crucial to understanding how the study was completed.

Study Schema

Biospecimen Collection for Analysis (each taken at visits 1 and 2)

NOTE: Biospecimens for this study are not currently available for request on CDAS. This tab only indicates what was collected.

Tissue Core Biopsies:

• Core 1 - Used for local pathology review to rule out malignancy and confirm continued study eligibility
• Core 2 - Used for Immunohistochemical analysis to determine CLS-B/CLS-B index/CLS-B/cm2 values
• Core 3-6 - Used in Quantitative Real-time PCR to determine TNFα/COX-2/IL1β /aromatase values
• Core 7 - Used for RNA analysis

Peripheral Blood Biomarkers:

• Used for RBC fatty acid analysis

Results/Findings:

Baseline levels of TNFα, IL1β, COX-2, and aromatase mRNAs did not differ significantly between the two treatment groups. The changes in the levels of TNFα (P = 0.50), IL1β (P = 0.52), COX-2 (P = 0.19), and aromatase (P = 0.12) after 12 weeks of treatment did not differ significantly between the two groups in the ITT cohort. Furthermore, in the preplanned evaluable population, there was also no statistically significant difference between the two arms in the change in pre- versus post-treatment levels in the tissue biomarker endpoints.