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| Name | Class |
|---|---|
| Breast Cancer Research Foundation | OTHER |
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The purpose of this research is to examine the effect of a broccoli sprout preparation on specific factors in breast tissue that are related to breast cancer risk and to assess whether sulforaphane a key component of broccoli sprouts increases the levels of protective enzymes in breast tissue. In addition, the investigators will also examine how acceptable the broccoli sprouts preparation is to the study participants.
A double-blind randomized Phase II chemoprevention trial of BSE versus placebo will be conducted in up to 35 women diagnosed with DCIS on core biopsy prior to their definitive surgery (study diagram below). The primary study endpoint will be a decrease in the mean proliferative rate measured by Ki67%.
Women diagnosed with DCIS on core or incisional/excisional biopsy scheduled for definitive surgery at Johns Hopkins Hospital will be recruited for this study. Participants will be placed on a cruciferous free diet for the 14 days prior to their surgical date and drink a randomized intervention beverage (mango juice with or without broccoli sprout extract). Additionally participants will provide 2 blood and 2 urine sample collections, report medication use and adverse events using prepared forms and complete a daily diet check list during the 14 day intervention. On the day of definitive breast surgery, 1-2 grams of breast tissue (including normal adjacent breast tissue) will be collected during surgery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Broccoli sprout extract | Experimental | Patients will be randomized to 14 day intervention of broccoli sprout extract and mango juice consisting of a dose of 100 µmols of sulforaphane dissolved in 150 mL mango juice once a day. |
|
| Mango juice | Placebo Comparator | Patients will be randomized to 14 day intervention of 150 mL mango juice without broccoli sprout extract extract once a day. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Broccoli sprout extract | Drug | 100 µmols of sulforaphane (dissolvable) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change in Mean Proliferative Rate Measured by Ki67% | Pathologists score the slides without knowledge of treatment assignment at the end of the study. All pre-post samples from one individual will be evaluated together. Quality control for these stains is performed routinely in the immunohistochemistry lab (using lymphoid tissue for Ki67). Initial scoring is performed where possible on a minimum of 3000 cells, by counting the number of positive cells divided by the total number of cells. DCIS lesions will be scored separately to adjacent normal tissue. The rationale for selecting Ki67 as a measure of cellular proliferation includes the robustness of the staining reaction, correlation with the S phase fraction of the cell cycle and mitotic index and that it can be successfully ascertained from core breast biopsies provided there is an adequate yield of epithelial cells. A negative value reflects a decrease in ki67 positive cells, therefore a decrease in cellular proliferation. | Change from baseline to 14 days post-intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Phase II Protein Expression as Assessed by Change in Cytoprotective Enzyme Expression Within Tumor | Phase II protein expression of cytoprotective enzymes known to be modulated by sulforaphane in DCIS specimens. Cytoprotective enzymes measured (NQ01 and AKR1C1 expression) based on immunohistochemical analysis. Expression was categorized by the study pathologist based on percentage of cells expressing antibody on the slide. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kala Visvanathan, MD | Johns Hopkins Bloomberg School of Public Health and Sidney Kimmel Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Medical Institution | Baltimore | Maryland | 21205 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Broccoli Sprout Extract and Mango Juice | Patients will be randomized to 14 day intervention of broccoli sprout extract consisting of a consistent dose of sulforaphane dissolved in mango juice compared to a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days). Broccoli sprout extract (sulforaphane): Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to receive a prepartion of broccoli sprout extract and mango juice. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study. |
| FG001 | Mango Juice | Patients will be randomized to 14 day intervention of mango juice without broccoli sprout extract. All women will be on a cruciferous free diet for the duration of the study (14 days).Mango juice without extract: Mango juice without broccoli sprout extract. B Mango juice: Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to receive a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Broccoli Sprout Extract and Mango Juice | Patients will be randomized to 14 day intervention of broccoli sprout extract consisting of a consistent dose of sulforaphane dissolved in mango juice compared to a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days). Broccoli sprout extract (sulforaphane): Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to either a prepartion of broccoli sprout extract and mango juice or a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Age collected on baseline survey. Participants had to be 18+ years old |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Absolute Change in Mean Proliferative Rate Measured by Ki67% | Pathologists score the slides without knowledge of treatment assignment at the end of the study. All pre-post samples from one individual will be evaluated together. Quality control for these stains is performed routinely in the immunohistochemistry lab (using lymphoid tissue for Ki67). Initial scoring is performed where possible on a minimum of 3000 cells, by counting the number of positive cells divided by the total number of cells. DCIS lesions will be scored separately to adjacent normal tissue. The rationale for selecting Ki67 as a measure of cellular proliferation includes the robustness of the staining reaction, correlation with the S phase fraction of the cell cycle and mitotic index and that it can be successfully ascertained from core breast biopsies provided there is an adequate yield of epithelial cells. A negative value reflects a decrease in ki67 positive cells, therefore a decrease in cellular proliferation. | All participants who completed the 14-day intervention on either study arm were included in analysis. | Posted | Mean | Standard Deviation | percentage of Ki67 | Change from baseline to 14 days post-intervention |
14 days during the intervention period (prior to first and 3 times during intervention)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Broccoli Sprout Extract and Mango Juice | Patients will be randomized to 14 day intervention of broccoli sprout extract consisting of a consistent dose of sulforaphane dissolved in mango juice compared to a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days). Broccoli sprout extract (sulforaphane): Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to either a prepartion of broccoli sprout extract and mango juice or a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
Eligible patients had to have their definitive breast cancer surgery at Johns Hopkins Hospital
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kala Visvanathan | Sidney Kimmel Comprehensive Cancer Center | 410-614-1112 | kvisvan1@jhu.edu |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| Mango juice |
| Drug |
150 mL of mango juice |
|
| Change from baseline to 14 days post-intervention |
| Pregnancy |
|
| BG001 | Mango Juice | Patients will be randomized to 14 day intervention of Mango juice without broccoli extract. All women will be on a cruciferous free diet for the duration of the study (14 days). Mango juice: Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to either a prepartion of broccoli sprout extract and mango juice or a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study. |
| BG002 | Total | Total of all reporting groups |
| Count of Participants |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Broccoli Sprout Extract and Mango Juice | Patients will be randomized to 14 day intervention of broccoli sprout extract consisting of a consistent dose of sulforaphane dissolved in mango juice. All women will be on a cruciferous free diet for the duration of the study (14 days). |
| OG001 | Mango Juice Without Extract | Patients will be randomized to 14 day intervention of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days). |
|
|
|
| Secondary | Phase II Protein Expression as Assessed by Change in Cytoprotective Enzyme Expression Within Tumor | Phase II protein expression of cytoprotective enzymes known to be modulated by sulforaphane in DCIS specimens. Cytoprotective enzymes measured (NQ01 and AKR1C1 expression) based on immunohistochemical analysis. Expression was categorized by the study pathologist based on percentage of cells expressing antibody on the slide. | Posted | Mean | Standard Deviation | % change of expression in tumor cells | Change from baseline to 14 days post-intervention |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 9 |
| 15 |
| EG001 | Mango Juice | Patients will be randomized to 14 day intervention of Mango juice without broccoli extract. All women will be on a cruciferous free diet for the duration of the study (14 days). Mango juice: Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to either a prepartion of broccoli sprout extract and mango juice or a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study. | 0 | 15 | 0 | 15 | 9 | 15 |
| intestional gas/bloating | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| upset stomach/indigestion | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| nausea/vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| abdominal cramps | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| appetite/ taste alteration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| light headed/ mild anxiety | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
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| D017437 |
| Skin and Connective Tissue Diseases |