Trial Outcomes & Findings for Study of Docosahexaenoic Acid (DHA) in Triple Negative Breast Cancer Survivors (NCT NCT01849250)

NCT ID: NCT01849250

Last Updated: 2021-12-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

Baseline to 12 weeks

Results posted on

2021-12-28

Participant Flow

Recruitment Period: May 1 ,2013 to December 31, 2015. All recruitment done in medical settings.

Of 65 participants enrolled, one was not eligible thus excluded from the study.

Participant milestones

Participant milestones
Measure	Placebo Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid (DHA) Docosahexaenoic Acid 1000 mg orally twice a day for 12 weeks.
Overall Study STARTED	32	32
Overall Study COMPLETED	25	29
Overall Study NOT COMPLETED	7	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid (DHA) Docosahexaenoic Acid 1000 mg orally twice a day for 12 weeks.
Overall Study Withdrawal by Subject	1	0
Overall Study Not Evaluable	5	3
Overall Study Screen Failure	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Docosahexaenoic Acid n=32 Participants DHA 1000 mg orally twice a day for 12 weeks.	Total n=64 Participants Total of all reporting groups	Placebo n=32 Participants Placebo orally twice a day for 12 weeks.
Age, Continuous	59.5 years n=7 Participants	59 years n=5 Participants	57 years n=5 Participants
Sex: Female, Male Female	32 Participants n=7 Participants	64 Participants n=5 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=7 Participants	47 Participants n=5 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=7 Participants	11 Participants n=5 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=7 Participants	6 Participants n=5 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=7 Participants	55 Participants n=5 Participants	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=5 Participants
Region of Enrollment United States	32 participants n=7 Participants	64 participants n=5 Participants	32 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 12 weeks

Population: 6 participants in the Placebo group and 1 participant in the DHA group were not evaluable due to tissue was not available quantitative RT-PCR.

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.

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid n=31 Participants Docosahexaenoic Acid (DHA) 1000 mg orally twice a day for 12 weeks.
Normal Breast Tissue Expression of Tumor Necrosis Factor Alpha (TNF-alpha) Levels Baseline	0.26 Log Transformed Relative ExpressionLevel Standard Deviation 0.93	0.08 Log Transformed Relative ExpressionLevel Standard Deviation 0.78
Normal Breast Tissue Expression of Tumor Necrosis Factor Alpha (TNF-alpha) Levels Post-Treatment	0.06 Log Transformed Relative ExpressionLevel Standard Deviation 0.92	0.16 Log Transformed Relative ExpressionLevel Standard Deviation 0.95
Normal Breast Tissue Expression of Tumor Necrosis Factor Alpha (TNF-alpha) Levels Post-treatment vs. Baseline Change	-0.22 Log Transformed Relative ExpressionLevel Standard Deviation 1.19	0.08 Log Transformed Relative ExpressionLevel Standard Deviation 0.99

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: 4 participants on the placebo arm and 1 participant on the DHA arm did not have a post treatment biopsy.

An indicator of whether a subject is detected with CLS-B or not.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid n=31 Participants Docosahexaenoic Acid (DHA) 1000 mg orally twice a day for 12 weeks.
Number of Participants With Crown-like Structures of the Breast (CLS-B) at Baseline and Post-treatment Baseline	2 Participants	4 Participants
Number of Participants With Crown-like Structures of the Breast (CLS-B) at Baseline and Post-treatment Post-treatment	3 Participants	3 Participants
Number of Participants With Crown-like Structures of the Breast (CLS-B) at Baseline and Post-treatment Positive both Baseline and Post-treatment	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Data were not collected.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Participants with adequate RNA available were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=14 Participants Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid n=23 Participants Docosahexaenoic Acid (DHA) 1000 mg orally twice a day for 12 weeks.
Breast Tissue Cox 2 mRNA Levels at Baseline and 12 Weeks Baseline COX-2	0.49 relative expression level Standard Deviation 1.35	0.31 relative expression level Standard Deviation 0.97
Breast Tissue Cox 2 mRNA Levels at Baseline and 12 Weeks Post-Treatment COX-2	-0.11 relative expression level Standard Deviation 1.30	0.22 relative expression level Standard Deviation 1.16

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Population: Participants with adequate RNA available were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid n=31 Participants Docosahexaenoic Acid (DHA) 1000 mg orally twice a day for 12 weeks.
Mean Difference in the Breast Tissue IL- Beta mRNA Levels of Tissue Biomarkers Baseline IL-Beta	0.62 relative expression level Standard Deviation 2.00	0.28 relative expression level Standard Deviation 1.50
Mean Difference in the Breast Tissue IL- Beta mRNA Levels of Tissue Biomarkers Post-treatment IL-Beta	0.23 relative expression level Standard Deviation 2.06	0.19 relative expression level Standard Deviation 2.07

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: Participants with adequate RNA available were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=22 Participants Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid n=30 Participants Docosahexaenoic Acid (DHA) 1000 mg orally twice a day for 12 weeks.
Mean Difference in the Breast Tissue Aromatase mRNA Levels of Tissue Biomarkers Baseline Aromatase	-0.38 relative expression level Standard Deviation 1.93	0.13 relative expression level Standard Deviation 2.38
Mean Difference in the Breast Tissue Aromatase mRNA Levels of Tissue Biomarkers Post-treatment Aromatase	-0.59 relative expression level Standard Deviation 2.13	0.06 relative expression level Standard Deviation 1.89

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Available blood samples.

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.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid n=30 Participants Docosahexaenoic Acid (DHA) 1000 mg orally twice a day for 12 weeks.
Red Blood Cell (RBC) Fatty Acid Level as a Surrogate of Compliance Baseline Omega3 index	5.03 percentage Standard Deviation 1.65	5.01 percentage Standard Deviation 1.13
Red Blood Cell (RBC) Fatty Acid Level as a Surrogate of Compliance Baseline DHA level	4.53 percentage Standard Deviation 1.5	4.47 percentage Standard Deviation 0.98
Red Blood Cell (RBC) Fatty Acid Level as a Surrogate of Compliance Post-Treatment Omega3 index	4.92 percentage Standard Deviation 1.68	11.95 percentage Standard Deviation 1.35
Red Blood Cell (RBC) Fatty Acid Level as a Surrogate of Compliance Post-Treatment DHA level	4.41 percentage Standard Deviation 1.48	11.2 percentage Standard Deviation 1.33
Red Blood Cell (RBC) Fatty Acid Level as a Surrogate of Compliance Post Treatment v. Baseline Change Omega3 index	-0.10 percentage Standard Deviation .068	6.99 percentage Standard Deviation 1.43
Red Blood Cell (RBC) Fatty Acid Level as a Surrogate of Compliance Post Treatment v. Baseline Change DHA level	-0.12 percentage Standard Deviation 0.59	6.78 percentage Standard Deviation 1.42

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Docosahexaenoic Acid

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=32 participants at risk Placebo orally twice a day for 12 weeks.	Docosahexaenoic Acid n=32 participants at risk Docosahexaenoic Acid 1000 mg orally twice a day for 12 weeks.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Blood and lymphatic system disorders Anemia	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.	6.2% 2/32 • Number of events 2 • Adverse events collected over 12 weeks of treatment.
Musculoskeletal and connective tissue disorders Arthralgia	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
Musculoskeletal and connective tissue disorders Back pain	6.2% 2/32 • Number of events 2 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Gastrointestinal disorders Bloating	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
Reproductive system and breast disorders Breast pain	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Injury, poisoning and procedural complications Bruising	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Gastrointestinal disorders Colitis	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
Gastrointestinal disorders Diarrhea	6.2% 2/32 • Number of events 3 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 2 • Adverse events collected over 12 weeks of treatment.
Gastrointestinal disorders Dyspepsia - Heart Burn	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Injury, poisoning and procedural complications Fall	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
General disorders Fatigue	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
Gastrointestinal disorders Flatulence	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
General disorders Flu like symptoms	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Gastrointestinal disorders Gastroesophageal reflux disease	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Gastrointestinal disorders Gastrointestinal disorders - Other: Burping	15.6% 5/32 • Number of events 5 • Adverse events collected over 12 weeks of treatment.	6.2% 2/32 • Number of events 2 • Adverse events collected over 12 weeks of treatment.
Gastrointestinal disorders Gastrointestinal disorders - Other: Diverticulitis	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
Gastrointestinal disorders Gastrointestinal disorders - Other: Loose stool	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
Nervous system disorders Headache	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	6.2% 2/32 • Number of events 2 • Adverse events collected over 12 weeks of treatment.
Cardiac disorders Heart failure, Congestive	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
Metabolism and nutrition disorders Hyperglycemia	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
General disorders Localized edema	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Musculoskeletal and connective tissue disorders Myalgia	6.2% 2/32 • Number of events 2 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Gastrointestinal disorders Nausea	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
Musculoskeletal and connective tissue disorders Neck pain	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
Gastrointestinal disorders Oral pain	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
Infections and infestations Otitis media	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
General disorders Pain	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, Chest Congestion	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Infections and infestations Sinusitis	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - other, Poison Ivy Rash	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
Skin and subcutaneous tissue disorders Skin infection	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Ear and labyrinth disorders Vertigo	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.	3.1% 1/32 • Number of events 1 • Adverse events collected over 12 weeks of treatment.
Gastrointestinal disorders Vomiting	6.2% 2/32 • Number of events 2 • Adverse events collected over 12 weeks of treatment.	0.00% 0/32 • Adverse events collected over 12 weeks of treatment.

Additional Information

Powel H. Brown, MD/Chair, Clinical Cancer Prevention

The University of Texas MD Anderson Cancer Center

Phone: 713-792-7734

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60