Broccoli Sprout Extract in Treating Women Who Have Had a Mammogram and Breast Biopsy
Study Details
Study Description
Brief Summary
RATIONALE: Broccoli sprout extract supplements may slow the growth of tumor cells or abnormal cells and may be an effective treatment for ductal carcinoma in situ and/or atypical ductal hyperplasia.
PURPOSE: This randomized phase II trial is studying how well broccoli sprout extract works in treating women with a diagnosis of breast cancer, ductal carcinoma in situ and/or atypical ductal hyperplasia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
-
To determine the correlation between supplemental sulforaphane (broccoli sprout extract) dose and concentrations of sulforaphane and its metabolites in blood and urine samples from women positive for cancer, ductal carcinoma in situ and/or atypical ductal hyperplasia.
-
To determine the effect of this supplement on biomarkers of prognosis in these patients.
-
To determine the effect of this supplement on HDAC inhibition in peripheral blood cell and normal and cancerous breast tissue samples from these patients.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
-
Sulforaphane Supplement: Patients receive oral broccoli sprout extract supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity.
-
Placebo: Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity.
Blood and urine samples are collected at baseline and after completion of study treatment for laboratory biomarker studies. Patients scheduled to undergo surgery (mastectomy or lumpectomy) also undergo breast tissue sample collection at baseline and at the time of surgery. Samples are analyzed for sulforaphane metabolism (isothiocyanate levels), HDAC activity (acetylated histone expression), cell proliferation (Ki-67 index by IHC), and apoptosis (TUNEL assay).
Patients complete questionnaires at baseline and periodically during study about their dietary history, family history, cruciferous vegetable intake, adverse events, and dietary and medication changes.
After completion of study therapy, patients are followed at/around 30 days.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sulforaphane Supplement Patients receive oral broccoli sprout extract supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. |
Dietary Supplement: broccoli sprout extract
Given orally
|
| Placebo Comparator: Placebo Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. |
Other: placebo
Given orally
|
Outcome Measures
Primary Outcome Measures
- Change in Isothiocyanate in Urine Samples as Assessed at Baseline and After Completion of Study Therapy [Baseline and end of study (up to 8 weeks)]
Isothiocyante including sulforaphane in micromolar (µM) concentration was measured following standard chemical measurement procedures and divided by the creatinine values in millimolar (mM) concentration.
- Change in Ki-67 as Assessed at Baseline and After Completion of Study Therapy [Baseline and end of study (up to 8 weeks)]
Ki-67 was measured through immunohistochemistry method. A modified H-score was recorded, which involved semi-quantitative assessment of both staining intensity (graded as 1-3 with 1 representing weak staining, 2 moderate staining, and 3 strong staining) and percentage of positive cells. The range of the H-score was 0-300. The maximum score indicates the strongest expression, the minimum score indicates no expression of positive tumor area.
- Change in Histone Deacetylase (HDAC) Activity as Assessed in Peripheral Blood Mononuclear Cells (PBMC) at Baseline and After Completion of Study Therapy [Baseline and End of Study (up to 8 weeks)]
PBMC HDAC activity was evaluated using the positive control, sodium butyrate.HDAC activity is expressed relative to PBMC protein content and negative control.
Secondary Outcome Measures
- Treatment Compliance [Baseline and end of study (up to 8 weeks)]
For treatment compliance, participants who take >=80% of the prescribed pills will be considered to be treatment-compliant.
Eligibility Criteria
Criteria
INCLUSION CRITERIA:
-
Diagnostic mammogram
-
English speaking
EXCLUSION CRITERIA:
-
Pregnancy (as determined by urine human chorionic gonadotropin (hCG) test)
-
No biopsy referral after diagnostic mammogram
-
Patient reported breast feeding
-
Significant active medical illness which in the opinion of the investigator would preclude protocol treatment
-
History of or active liver disease or baseline total bilirubin greater than institutional upper limit of normal
-
Patient reported allergy or sensitivity to cruciferous vegetables
-
Use of oral antibiotics within three months prior to randomization
-
Oral steroid therapy at enrollment
-
Current therapy with valproate acid or SAHA
-
Current use of nutrient supplements or herbal remedies containing sulforaphane and unwillingness or inability to quit 72 hours prior to randomization and for the duration of the trial
-
Radiation for currently-diagnosed disease prior to or during study supplementation
-
Chemotherapy for currently-diagnosed disease prior to or during study supplementation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Knight Cancer Institute at Oregon Health and Science University | Portland | Oregon | United States | 97239-3098 |
Sponsors and Collaborators
- OHSU Knight Cancer Institute
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Jackilen Shannon, PhD, OHSU Knight Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000634111
- R21CA132236
- P30CA069533
- OHSU-4702
Study Results
Participant Flow
| Recruitment Details | This clinical trial was conducted between 12/23/2008 to 3/27/2013 at Oregon Health and Science University's (OHSU) Center for Women's Health Breast Center in Portland, OR. English-speaking women were recruited to participate in the study based on the following inclusion criteria: ≥ 21 years, diagnostic mammogram with results that require biopsy. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Sulforaphane Supplement | Placebo |
|---|---|---|
| Arm/Group Description | Patients receive oral broccoli sprout extract supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. broccoli sprout extract: Given orally | Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. placebo: Given orally |
| Period Title: Treatment Period | ||
| STARTED | 27 | 27 |
| COMPLETED | 24 | 19 |
| NOT COMPLETED | 3 | 8 |
| Period Title: Treatment Period | ||
| STARTED | 24 | 24 |
| Completed Final Visit | 24 | 24 |
| COMPLETED | 24 | 24 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Sulforaphane Supplement | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Patients receive oral broccoli sprout extract supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. broccoli sprout extract: Given orally | Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. placebo: Given orally | Total of all reporting groups |
| Overall Participants | 27 | 27 | 54 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
24
88.9%
|
18
66.7%
|
42
77.8%
|
| >=65 years |
3
11.1%
|
9
33.3%
|
12
22.2%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
53.5
(9.5)
|
55.3
(14.3)
|
54.4
(12.1)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
27
100%
|
27
100%
|
54
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
1
3.7%
|
1
3.7%
|
2
3.7%
|
| Asian |
0
0%
|
1
3.7%
|
1
1.9%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
1
3.7%
|
1
1.9%
|
| White |
26
96.3%
|
24
88.9%
|
50
92.6%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
27
100%
|
27
100%
|
54
100%
|
Outcome Measures
| Title | Change in Isothiocyanate in Urine Samples as Assessed at Baseline and After Completion of Study Therapy |
|---|---|
| Description | Isothiocyante including sulforaphane in micromolar (µM) concentration was measured following standard chemical measurement procedures and divided by the creatinine values in millimolar (mM) concentration. |
| Time Frame | Baseline and end of study (up to 8 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Sulforaphane Supplement | Placebo |
|---|---|---|
| Arm/Group Description | Patients receive oral broccoli sprout extract supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. broccoli sprout extract: Given orally | Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. placebo: Given orally |
| Measure Participants | 27 | 27 |
| Mean (Standard Error) [µM/mM creatinine] |
1.00
(0.334)
|
-0.05
(0.02)
|
| Title | Change in Ki-67 as Assessed at Baseline and After Completion of Study Therapy |
|---|---|
| Description | Ki-67 was measured through immunohistochemistry method. A modified H-score was recorded, which involved semi-quantitative assessment of both staining intensity (graded as 1-3 with 1 representing weak staining, 2 moderate staining, and 3 strong staining) and percentage of positive cells. The range of the H-score was 0-300. The maximum score indicates the strongest expression, the minimum score indicates no expression of positive tumor area. |
| Time Frame | Baseline and end of study (up to 8 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Maximum two observations (pre- and post- treatments) were expected per participant. Linear mixed effect models were used to calculate adjusted least square means (LSMEANS) and 95% confidence intervals,& to test the statistical significance of the difference between pre- and post- treatments within each group, as well as between treatment groups. |
| Arm/Group Title | Benign Tissue; Ki-67 | DCIS Tissue; Ki-67 | Invasive Ductal Carcinoma Tissue; Ki-67 |
|---|---|---|---|
| Arm/Group Description | Sulforaphane Supplement = 23, Placebo = 25 | Sulforaphane Supplement= 6, Placebo = 13 | Sulforaphane Supplement= 7, Placebo= 6 |
| Measure Participants | 48 | 19 | 13 |
| Sulforaphane Supplement |
-1.39
|
0.42
|
0.98
|
| Placebo |
0.23
|
-0.48
|
0.28
|
| Title | Change in Histone Deacetylase (HDAC) Activity as Assessed in Peripheral Blood Mononuclear Cells (PBMC) at Baseline and After Completion of Study Therapy |
|---|---|
| Description | PBMC HDAC activity was evaluated using the positive control, sodium butyrate.HDAC activity is expressed relative to PBMC protein content and negative control. |
| Time Frame | Baseline and End of Study (up to 8 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| PBMCs available pre-/post-intervention. |
| Arm/Group Title | Sulforaphane Supplement | Placebo |
|---|---|---|
| Arm/Group Description | Patients receive oral broccoli sprout extract supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. broccoli sprout extract: Given orally | Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. placebo: Given orally |
| Measure Participants | 23 | 24 |
| Mean (Standard Error) [pmol/min/mg protein] |
-80.39
(48.53)
|
27.52
(32.58)
|
| Title | Treatment Compliance |
|---|---|
| Description | For treatment compliance, participants who take >=80% of the prescribed pills will be considered to be treatment-compliant. |
| Time Frame | Baseline and end of study (up to 8 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Sulforaphane Supplement | Treatment |
|---|---|---|
| Arm/Group Description | Patients receive oral broccoli sprout extract supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. broccoli sprout extract: Given orally | Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. placebo: Given orally |
| Measure Participants | 27 | 27 |
| Number [participants] |
19
70.4%
|
16
59.3%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Sulforaphane Supplement | Placebo | ||
| Arm/Group Description | Patients receive oral broccoli sprout extract supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. broccoli sprout extract: Given orally | Patients receive oral placebo supplementation three times daily for 2-8 weeks in the absence of unacceptable toxicity. placebo: Given orally | ||
All Cause Mortality |
||||
| Sulforaphane Supplement | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Sulforaphane Supplement | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/27 (0%) | 0/27 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Sulforaphane Supplement | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/27 (29.6%) | 9/27 (33.3%) | ||
| Cardiac disorders | ||||
| Heartburn | 1/27 (3.7%) | 0/27 (0%) | ||
| Gastrointestinal disorders | ||||
| Bloating | 5/27 (18.5%) | 5/27 (18.5%) | ||
| Gas/Flatulence | 1/27 (3.7%) | 4/27 (14.8%) | ||
| Diarrhea | 1/27 (3.7%) | 2/27 (7.4%) | ||
| Nausea/Vomiting | 0/27 (0%) | 1/27 (3.7%) | ||
| Immune system disorders | ||||
| Allergy | 0/27 (0%) | 1/27 (3.7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Bruising | 1/27 (3.7%) | 1/27 (3.7%) | ||
| Arthritic pain | 1/27 (3.7%) | 1/27 (3.7%) | ||
| Cramping | 1/27 (3.7%) | 0/27 (0%) | ||
| Knee pain | 1/27 (3.7%) | 0/27 (0%) | ||
| Shoulder pain | 1/27 (3.7%) | 0/27 (0%) | ||
| Nervous system disorders | ||||
| Headache | 1/27 (3.7%) | 3/27 (11.1%) | ||
| Taste Alteration | 0/27 (0%) | 2/27 (7.4%) | ||
| Tingling tongue sensation | 0/27 (0%) | 1/27 (3.7%) | ||
| More sleep | 0/27 (0%) | 1/27 (3.7%) | ||
| Sleeping less | 0/27 (0%) | 1/27 (3.7%) | ||
| Insomnia | 0/27 (0%) | 1/27 (3.7%) | ||
| Psychiatric disorders | ||||
| Feeling tired | 0/27 (0%) | 1/27 (3.7%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Jackilen Shannon |
|---|---|
| Organization | Oregon Health & Science University |
| Phone | 541-706-6861 |
| shannoja@ohsu.edu |
- CDR0000634111
- R21CA132236
- P30CA069533
- OHSU-4702