Broccoli Sprout Extract in Treating Women Who Have Had a Mammogram and Breast Biopsy

Breast Cancer Clinical Trial

Official title:

Sulforaphane: A Dietary Histone Deacetylase (HDAC) Inhibitor in Ductal Carcinoma in Situ (DCIS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00843167
• Other study ID #: CDR0000634111
• Secondary ID: R21CA132236P30CA
• Status: Completed
• Phase: Phase 2
• First received: February 12, 2009
• Last updated: April 25, 2017
• Start date: August 2009
• Est. completion date: December 2013

Study information

• Verified date: October 2015
• Source: OHSU Knight Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 21 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Carcinoma in Situ
• Precancerous Condition
• Precancerous Conditions

Intervention

Dietary Supplement:
• broccoli sprout extract
Given orally

Other:
• placebo
Given orally

Locations

Country	Name	City	State
United States	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
OHSU Knight Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Isothiocyanate in Urine Samples as Assessed at Baseline and After Completion of Study Therapy	Isothiocyante including sulforaphane in micromolar (µM) concentration was measured following standard chemical measurement procedures and divided by the creatinine values in millimolar (mM) concentration.	Baseline and end of study (up to 8 weeks)
Primary	Change in Ki-67 as Assessed at Baseline and After Completion of Study Therapy	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.	Baseline and end of study (up to 8 weeks)
Primary	Change in Histone Deacetylase (HDAC) Activity as Assessed in Peripheral Blood Mononuclear Cells (PBMC) at Baseline and After Completion of Study Therapy	PBMC HDAC activity was evaluated using the positive control, sodium butyrate.HDAC activity is expressed relative to PBMC protein content and negative control.	Baseline and End of Study (up to 8 weeks)
Secondary	Treatment Compliance	For treatment compliance, participants who take >=80% of the prescribed pills will be considered to be treatment-compliant.	Baseline and end of study (up to 8 weeks)