Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Other Dietary Supplements

Sulforaphane

Protective Agents

Sulforaphane four tablets 2 times per day with breakfast and dinner each dose contains approximately 120 micromole of Sulforaphane

Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner

Sulforaphane (SF) is a naturally occurring substance (phytochemical) found in cruciferous vegetables.

Placebo

Jian-Min Yuan, MD, PhD

This research study involves taking an experimental anti-cancer dietary supplement called Sulforaphane (SF) or a placebo (product without any supplement content) over a period of twelve months in order to determine if it is a useful dietary supplement for prevention of lung cancer in humans.

The main goals of this research study are:

1. To learn about the effects of giving Sulforaphane (SF) to former smokers who are still at high risk of developing cancer due to their smoking history and whether or not their condition improves, stays the same or becomes worse after Sulforaphane (SF) is given.
2. To learn whether Sulforaphane (SF) might reverse some of the lung cell changes associated with future development of lung cancer.

Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers

Randomized Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers

To explore if daily oral dose of 120 micromole SF can modulate the changes in bronchial dysplasia from endoscopic biopsies in former smokers at high risk for lung cancer.

To explore if daily oral dose of 120 micromole SF can inhibit level of cell proliferation marker Ki-67 in bronchial biopsies of former smokers at high risk for lung cancer.

To explore if daily oral dose of 120 micromole SF can induce apoptosis markers caspase-3 and TUNEL in bronchial biopsies in former smokers at high risk for lung cancer.

To explore if daily oral dose of 120 micromole SF can modulate the changes of the lung cancer-related gene expression markers in bronchial epithelia in former smokers at high risk for lung cancer.

To explore if daily oral dose of 120 micromole SF can modulate the changes of bronchial premalignant lesions-related gene expression markers in former smokers at high risk for lung cancer.

To explore if daily oral dose of 120 micromole SF can modulate the similar changes of the gene expression markers in nasal epithelia.

To determine the safety and toxicity of daily oral dose of 120 micromole SF in former smokers at high risk for lung cancer by monitoring and recording any potential SF-related adverse events (both expected and unexpected events).

National Cancer Institute (NCI)

Jian-Min Yuan, MD

Principal Investigator

Symptoms and General Pathology

Carcinogenesis

Neoplastic Processes

Broccoli Sprout Extract Beverage: 600 micromole glucoraphanin and 40 micromole sulforaphane dissolved in 100 mL dilute pineapple and lime juice daily for 84 days.

Broccoli Sprout Extract Beverage

100 mL of dilute pineapple and lime juice daily for 84 days.

placebo beverage

Thomas W Kensler, PhD

This study is a 12 week placebo-controlled Phase II broccoli sprout intervention to be conducted in Qidong, P.R. China. One thousand two hundred people from the farming townships will be screened and three hundred eligible individuals will be enrolled in the study. Participants will be randomized into two treatment groups: one will receive a juice beverage containing glucoraphanin- and sulforaphane-rich broccoli sprout extract, pineapple juice, lime juice, and water and the other will receive a placebo beverage containing pineapple juice, lime juice and water. Participants will drink their assigned beverage every evening and provide biweekly urine samples and monthly blood samples. The principal endpoints of this study are pharmacokinetic evaluation of elimination of glucoraphanin/sulforaphane and their metabolites in urine and pharmacodynamic evaluation through measures of urinary levels of exposure biomarkers for dietary and air-borne toxins, which are known to be high in this population.

Broccoli Sprout Intervention in Qidong, P.R. China

Urinary excretion of benzene mercapturic acid (S-PMA) in 12 hour overnight void at 12 weeks

Micromoles of urinary sulforaphane metabolites excreted over 24 hours after consuming the 84th dose.

Johns Hopkins University

National Institute of Environmental Health Sciences (NIEHS)

Qidong Liver Cancer Institute

University of Pittsburgh

University of Minnesota

Johns Hopkins Bloomberg School of Public Health

Broccoli Sprout Extract Beverage : Broccoli Sprout Extract Beverage: 600 micromole glucoraphanin and 40 micromole sulforaphane dissolved in 100 mL dilute pineapple and lime juice daily for 84 days.

placebo beverage : 100 mL of dilute pineapple and lime juice daily for 84 days.

Placebo Beverage

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

China

Region of Enrollment

Thomas W. Kensler, PhD

Analyses were conducted on all urine samples provided by study participants at week 12.

Effect of Treatment on Levels of Air Toxics Mercapturic Acids Over Intervention Period

placebo beverage: 100 mL of dilute pineapple and lime juice daily for 84 days.

Broccoli Sprout Extract Beverage: Broccoli Sprout Extract Beverage: 600 micromole glucoraphanin and 40 micromole sulforaphane dissolved in 100 mL dilute pineapple and lime juice daily for 84 days.

Levels of Sulforaphane and Its Metabolites at the End of Intervention Period (After 84 Daily Doses)

Overall Study

Skin and Connective Tissue Diseases

Heart and Blood Diseases

Substance Related Disorders

Wounds and Injuries

Breast Neoplasms

Cardiotoxicity

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Doxorubicin

Liposomal doxorubicin

Processed SFN-rich extract will be purchased in form of caplets from Nutramax Laboratories, Inc. 2208 Lakeside Blvd Edgewood, MD 21040. Caplets containing SFN-rich broccoli sprout extracts from Nutramax Labs will be dispensed to participants in sealed bottles with instructions to keep them in a household freezer. Size of the caplet will be about 2 cm in length. Dosing will be based on weight and will be dosed daily for 12 weeks.

Placebo caplets will comprise of microcrystalline cellulose from Nutramax Labs and will be dispensed to participants in sealed bottles with instructions to keep them in a household freezer. Placebo pills will be identical in appearance to the sulforaphane pills and will be dosed in a similar manner (identical number of pills based on weight, daily dosing and for 12 weeks)

The participants will be dosed, based on weight, in a double-blind fashion with identical appearing placebo or sulforaphane caplets in a daily dose for 12 weeks of: two caplets for individuals \<100 lb., four caplets for individuals 100-200 lb. and eight caplets for individuals \>200 lb. Avmacol or placebo will be prescribed by Dr. Awasthi and will be dispensed by local pharmacy or study coordinators at TTUHSC/UMC Lubbock. We will be doing pill counts to make sure that volunteers have used as directed. We will measure the Sulforaphane level in plasma by well-established method.

sulforaphane

Placebo Oral Tablet

sharda p singh

Catherine Jones, MD

sharda p singh, PhD

nandini Nair, MD PhD

catherine Jones, MD

sriman swarup, MD

Alexander Philipovskiy, MD PhD

Trey Putnam, PhD

Pooja Sethi, MD

Cardiomyopathy is a major complication of doxorubicin (DOX) chemotherapy, and 10-21% of breast cancer patients receiving DOX experience compromised cardiac function. Recent advancements have increased cancer survivorship but it remains clinically challenging to mitigate the cardiotoxic side effects. Although there are several strategies used to reduce the occurrence and severity of DOX-induced cardiotoxicity, they are not particularly effective. Hence, there is an urgent need to develop new strategies that prevent the cardiotoxic effects of DOX but maintain its potency as a cancer therapy. Because the cellular events responsible for the antitumor activity of DOX and DOX-induced cardiotoxicity are distinctly different, it may be possible to develop therapies that selectively mitigate DOX-induced cardiotoxicity. Thus, the investigators propose to test an adjuvant therapy that combines the phytochemical sulforaphane (SFN) with DOX to attenuate DOX-induced cardiomyopathy. SFN activates the transcription factor Nrf2 and induces defense mechanisms in normal cells. Furthermore, SFN inhibits carcinogenesis and metastases and enhances cancer cell sensitivity to DOX, seemingly through Nrf2-independent mechanisms. SFN has also been tested in several clinical trials, although never together with DOX. Our early animal studies suggest that by activating Nrf2, SFN selectively protects the mouse and rat from DOX cardiotoxicity, enhances survival and enhances the effects of DOX on cancer growth in a rat breast cancer model. The investigators suspect that SFN affects DOX metabolism in cancer cells to enhance tumor regression, or it may synergistically activate other key antitumor mechanisms. Hence, SFN may improve the clinical outcome of cancer therapy by (1) attenuating DOX cardiotoxicity and (2) enhancing the effects of cancer treatment on the tumor. Our hypothesis is that SFN protects the heart from DOX-mediated cardiac injury without altering the antitumor efficacy of DOX. In Aim 1, the investigators will conduct an early-phase clinical trial to determine if SFN is safe to administer to breast cancer patients undergoing DOX chemotherapy. In Aim 2, the investigators will determine if SFN decreases DOX-induced inflammatory responses and enhances Nrf2- and SIRT1-target gene expression in breast cancer patients. Notably, transcript and protein signatures in peripheral blood mononuclear cells (PBMCs) can predict cardiac function in patients undergoing DOX chemotherapy for breast cancer. The investigators will also determine if SFN/DOX treatment activates Nrf2- and SIRT1-dependent gene expression, alters the levels of biomarkers for presymptomatic DOX-cardiotoxicity and mitigates the generation of cardiotoxic metabolites in PBMCs and plasma. These studies will facilitate the development of SFN co-treatment as a strategy to enhance the efficacy and safety of DOX cancer therapy.

Determine whether nutritional supplement sulforaphane (SFN) is safe to administer to breast cancer patients undergoing doxorubicin (DOX) chemotherapy. The investigators have identified biomarkers for presymptomatic detection of DOX cardiotoxicity in breast cancer patients and reported that SFN alleviates DOX-induced cardiac toxicity while maintaining its anti-tumor activity in an animal model of breast cancer. SFN is in various stages of preclinical and clinical trials against different types of cancer but its safety and effects on identified markers have never been tested in patients treated with DOX. Sulforaphane is a generally recognized as a safe (GRAS) compound and this compound is currently in 61 different clinical trials including, Cystic Fibrosis, COPD, Melanoma, Breast and prostate cancer etc. (https://clinicaltrials.gov/ct2/results?term=sulforaphane\&pg=1). Avmacol Extra Strength, (Nutramax Laboratories Consumer Care, Inc. Edgewood, MD 21040) an over-the-counter dietary supplement containing broccoli seed and sprout extracts that is rich with sulforaphane, will be used in this study. This is an FDA regulated trial using an investigational drug under IND 141682. Dose considerations were made on the basis of the ongoing clinical trial "Effects of Avmacol Extra Strength® in the Oral Mucosa of Patients Following Curative Treatment for Tobacco-related Head and Neck Cancer" (https://clinicaltrials.gov/ct2/show/NCT03268993). Furthermore, Avmacol Extra Strength has never been tested as an adjuvant to try and protect the heart from DOXs harmful effects. . Therefore, the investigators are proposing to do an early-clinical trial to assess SFN safety in DOX-treated patients and possibly prevent DOX-cardiotoxicity in breast cancer patients.

Our hypothesis is that SFN protects the heart from DOX-mediated cardiac injury without affecting its antitumor efficacy. Here, the investigators will test SFN in combination with DOX-based chemotherapy for breast cancer; the investigators will assess its safety, cardio-protective properties, and anti-cancer efficacy. The investigators will also examine the effect of SFN on the expression of several biomarkers that indicate when a patient cannot tolerate DOX.1 To test our hypothesis, the investigators propose the following Specific Aims.

Aim 1: Demonstrate that co-administration of SFN protects the heart and is not associated with toxicity or reduced tumor response in breast cancer patients undergoing DOX chemotherapy.

The investigators propose a pilot clinical trial to assess the safety of SFN as a co-treatment with DOX chemotherapy. Strategy: Up to seventy breast cancer patients prescribed DOX chemotherapy will be consented then randomly assigned to receive either SFN or placebo during DOX chemotherapy. This sample size includes an additional 10 participants to allow for potential attrition. There will be a 50-50 chance of receiving SFN. The patients will be recruited from the Breast Cancer Clinic (Dr. Jones and Philipovskiy) in the Southwest Cancer Center at TTUHSC/UMC Lubbock. Cardiac function with echocardiography will be assessed and compared between arms for evidence of substantive decrease in DOX cardiotoxicity with SFN compared to placebo. Tumor size will also be compared (based on RECIST criteria) between treatment arms. The investigators will monitor treatment-emergent symptoms, hematological parameters of cancer therapy toxicity, and renal and hepatic function. Blood samples will be collected to assay markers of cardiotoxicity, including B-type natriuretic peptide and troponin.

Aim 2: Determine if SFN alters the levels of known biomarkers of DOX cardiotoxicity and affects the expression of SIRT1- and Nrf2-target genes.

The investigators will measure changes in transcript and protein biomarkers of pre-symptomatic DOX-cardiotoxicity in response to SFN, and will determine if SFN promotes SIRT1- and Nrf2-dependent gene expression. Because Nrf2 upregulates certain detoxifying enzymes, the investigators will measure the plasma levels of cardiotoxic metabolites, doxorubicinol (DOXol). Strategy: Blood will be collected before the start of DOX chemotherapy and after each treatment cycle to isolate peripheral blood mononuclear cells (PBMCs) and prepare plasma. In lieu of tissue biopsies, PBMCs will be used to examine SIRT1 and Nrf2 activity and target gene expression. Multiplex arrays will be used to measure plasma cytokine levels, and plasma DOX metabolites will be assessed with ultrahigh performance liquid chromatography-tandem mass spectrometry. These experiments will provide initial evidence to indicate that SFN activates SIRT1 and Nrf2 pathways in non-cancer tissue of breast cancer patients.

Impact: This will be the first clinical study to assess the safety of SFN as a co-treatment with DOX to mitigate cardiotoxicity in breast cancer patients. Positive findings will be used to justify a larger randomized controlled trial. Subjects will be randomized at a 1:1 ratio.

Study Design and Procedures Study Design. The investigators intend to include up to 70 DOX-naïve women diagnosed with breast cancer undergoing neoadjuvant chemotherapy with no prior cardiac disease and who will receive DOX without Her-2 receptor antagonists (to eliminate possibility of secondary side effects) as part of their clinical care. These potential subjects will be recruited in a randomized, controlled, double blinded pilot study comparing SFN to placebo. The study will be conducted at the Texas Tech University Health Sciences Center, and University Medical Center. The trial will be approved by our local IRB and registered at clinicaltrials.gov. UMC cancer center pharmacist Ajoke A. Tijani, RPh. (Tijani@umchealthsystem.com) will receive placebo and test compound from supplier and will dispense them to test subjects.

Randomization will be achieved with assignment of a subject ID to the study subject. The list of subject IDs will be subsequently assigned either study drug or placebo using a randomizer software such as (www.randomizer.org). The pharmacist dispensing the medication will be aware of the study IDs in relation to the patient identity, in order to be able to dispense the test drug or the placebo per their assigned status as test or control subjects.

Study Drug and Placebo. Processed SFN-rich extract will be purchased in form of caplets from Nutramax Laboratories, Inc. 2208 Lakeside Blvd Edgewood, MD 21040. Caplets containing SFN-rich broccoli sprout extracts or microcrystalline cellulose (placebo) also from Nutramax Labs will be dispensed to participants in sealed bottles with instructions to keep them in a household freezer. Size of the caplet will be about the size of a 1000 mg Vit C pill (about 2 cm in length). The participants will be dosed, based on weight, in a double-blind fashion with identical appearing placebo or SFN caplets in a daily dose for 12 weeks of: two caplets for individuals \<100 lb., three caplets for individuals 100-200 lb. and four caplets for individuals \>200 lb. Avmacol Extra Strength or placebo will be prescribed by Dr. Jones and Philipovskiy and will be dispensed by local pharmacy or study coordinators at TTUHSC/UMC Lubbock. The investigators will be doing pill counts to make sure that volunteers have used as directed. The investigators will measure the Sulforaphane level in plasma by well-established method. 26 The drug and the placebo will be stored at the South West Cancer Center pharmacy based on manufacturer based guidelines and dispensed to each participant at their baseline visit then at DOX infusion visits 1, 2, and 3. Patients will be expected to maintain at least an 80% adherence to the medication regimen, in the absence of prohibitive toxicity. Adherence will be monitored through therapeutic drug level (Plasma sulforaphane levels of 120 ng/ml) monitoring as mentioned above and pill counts. For subjects who do not meet 80% compliance, they will be instructed on the importance of taking the pills as directed, but if their next visit demonstrates less than 80% compliance, they will be withdrawn from the study. As long as participants complete their 4th cycle of DOX chemotherapy treatment the investigators will still use their study data during analysis. If side effects are noted, patient will be asked to notify the study team of the same and will be evaluated within a suitable time frame based on severity of side effects.

SFN is a safe natural isolate. Above doses (30mg/caplet) are considered adequate to maintain intended therapeutic drug levels, while maintaining a simple study design and without significant concerns for drug toxicity It has been used in several clinical trials from doses ranging from 2-200 µmol/day for 2-28 weeks in 25-80 years old subjects without significant side-effects or toxicity (https://clinicaltrials.gov/ct2/results?term=sulforaphane\&Search=Search), yet never in combination with DOX.

Statistical Considerations Data for the primary endpoint (DOX cardiotoxicity) and other binary outcomes will be summarized by treatment arm as number and proportion per arm. The change in DOX-cardiotoxicity rate with SFN compared to placebo will be assessed with a 1-sided Z-test (see Sample-size justification). Tumor size, plasma cardiac biomarkers, cardiac ejection fraction, DOX metabolite levels will be summarized by treatment arm and time point as means and standard deviations and graphed as box plots and profile plots. The investigators will adhere to ANOVA distributional assumptions so that appropriate data transformations can be applied. Data for each continuous variable will be analyzed for differences in group means at each time point with ANOVA or Mann-Whitney-Wilcoxon non-parametric tests at each time point. These tests will employ a more-stringent alpha = 0.02 significance level to adjust for the multiple comparisons without overinflating type II error. For subjects withdrawn from the study or do not complete the study for any reason, as long as they completed their 4th cycle of DOX chemotherapy treatment the investigators will still use their study data during analysis.

Sample-size justification. The number of subjects (35 per treatment arm; 70 total; the investigators expect some attrition, which this sample size addresses) is based on the primary endpoint of DOX-induced cardiac dysfunction, the rate of which was recently observed at our previous institution (UAMS) to be \~25%1. The investigators expect that SFN will decrease this to 5%. The cardiotoxicity rates for each arm will be compared via 1-sided pooled-variance Z-test at an alpha = 0.10. The statistical power of this test, conducted as described, needs to exceed 80% in order for our study to be generally recognized as having adequate statistical power. Our sample size provides the 1-sided pooled-variance Z-test with 83.2% power at 10% alpha to detect the expected 20-point decrease in DOX-toxicity rates from 25% in the placebo arm to 5% in the SFN arm.

The formal consent of each subject, using the IRB-approved consent form, will be obtained before that subject is submitted to any study procedure.

We plan to include 70 DOX-naïve women with breast cancer undergoing neoadjuvant chemotherapy, with no prior cardiac disease and who will receive DOX without Her-2 receptor antagonists as part of their clinical care. Potential subjects will be recruited in a randomized, controlled; double blinded pilot study comparing SFN to placebo. Study will be conducted at the TTUHSC and UMC. The trial is approved by the institutional IRB and will be registered at clinicaltrials.gov. UMC cancer center pharmacist Ajoke A. Tijani, RPh. will receive placebo and test compound from supplier and will dispense them to test subjects. Randomization will be done with assignment of a subject ID to the study subject. The list of subject IDs will be subsequently assigned to either study drug or placebo using a randomizer software.

Protective Effects of the Nutritional Supplement Sulforaphane on Doxorubicin-Associated Cardiac Dysfunction

Phase II Trial of Effects of the Nutritional Supplement Sulforaphane on Doxorubicin-Associated Cardiac Dysfunction (CRI18-026)

All data generated from this project will be disseminated across the scientific community as rapidly as possible while adhering to the NIH Grants Policy on Availability of Research Results: Publications, Intellectual Property Rights, and Sharing Research Resources, issued in November 2016. The data will be available in password protected files, accessible only to investigators and with read only access to the databases. We will follow the guidelines established by NIH for Data Sharing Policy and Implementation and will ensure that all NIH privacy protection procedures are followed. We will make the dataset available to qualified investigators within 6 months of acceptance of the manuscript describing the main study findings. Investigators who request to use the dataset will be required to obtain IRB approval and to sign a data use agreement form before release of the data.

2D Echo will be used to measure cardiac function amongst patients on DOX therapy who are exposed to sulforaphane or placebo.

Troponin will be used to assess for cardiotoxicity amongst patients on DOX therapy who are exposed to sulforaphane or placebo.

We will use PET imaging for comparison of change in tumor size for patients on DOX therapy with or without sulforaphane.

Texas Tech University Health Sciences Center

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Cancer

Active sulforaphane distributed in capsules each containing broccoli sprout grain

Inactive substances (methylcellulose) with identical capsule and portion distribution

Patients will be randomly classified into two groups - verum and placebo. The patients in the experimental arm will receive capsules with broccoli sprout grain containing a total of 90mg sulforaphane active substance per day over one year as nutrition supplement whereas patients assigned to the placebo group will receive inactive substance (methylcellulose) with identical capsule and portion distribution.

Verum, broccoli sprout grain

Patients assigned to the placebo group will receive inactive substance (methylcellulose) with identical capsule and portion distribution as the experimental arm.

placebo

Peter Schemmer, Prof. Dr. med.

Vladimir J. Lozanovski, M.D.

Ingrid Herr, Prof. Dr.

The goal of the POUDER trial is to determine the feasibility of a randomized controlled trial regarding the application of freeze-dried broccoli sprouts rich in sulforaphane and quercetin in patients with advanced pancreatic ductal adenocarcinoma that receive palliative chemotherapy.

Pilot Study Evaluating Broccoli Sprouts in Advanced Pancreatic Cancer [POUDER Trial]

Urine analysis as marker of substance systemic bioavailability (conversion of the precursor glucoraphanin to the active drug substance sulforaphane). Urine analysis serves as control of the regular intake of the test substance as well.

Main objective is to test the feasibility of a randomized controlled trial regarding the application of freeze-dried broccoli sprouts rich in sulforaphane and quercetin in patients with advanced, surgically non-resectable pancreatic ductal adenocarcinoma treated with palliative chemotherapy

Disease status (cancer progress or regress): CT-imaging staging (if available) and serum tumor markers (CEA and CA-19-9) peaks as additional parameters that provide insight into disease status.

German Cancer Research Center

Heidelberg University

Prof. Dr. med. Peter Schemmer, MBA

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Phenethyl isothiocyanate

Phenethylisothiocyanate

Four weeks SFN-rich broccoli sprout extract (BSE) capsules: 200µmol of sulforaphane (SFN) daily, 2 capsules (1 capsule B.I.D.) daily

Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily

Four weeks SFN-rich broccoli sprout extract (BSE) capsules: 200µmol of SFN, 2 capsules (1 capsule B.I.D.) daily

SFN-rich broccoli sprout extract capsules

Gelatin capsule containing microcrystalline cellulose.

Jackilen Shannon, PhD

The objective of the study is to identify mechanisms by which compounds found in cruciferous vegetables alter gene expression via epigenetic modifications (changes in gene expression) and may prevent prostate cancer development.

The investigators have found that sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, inhibits histone deacetylase (HDAC) activity in human colorectal and prostate cancer cells.

Prostate cancer is the most frequently diagnosed non-cutaneous cancer and is the second leading cause of cancer death in American men. The precise etiologic factors that initiate and enhance the progression of prostate cancer remain unknown, but epigenetic alterations and diet/lifestyle factors have come forth as significant contributing factors. Epidemiologic studies suggest that cruciferous vegetable intake decreases the risk for prostate cancer. The long-term goal of this proposal is to identify mechanisms by which dietary compounds, such as those found in cruciferous vegetables decrease prostate cancer risk. The objective of the study is to identify mechanisms by which compounds found in cruciferous vegetables alter gene expression via epigenetic modifications and may prevent prostate cancer development.

The investigators have found that SFN, an isothiocyanate found in cruciferous vegetables, inhibits HDAC activity in human colorectal and prostate cancer cells.

Targeting the epigenome, including the use of HDAC and DNA methyltransferase (DNMT) inhibitors, is an evolving strategy for cancer chemoprevention and both have shown promise in cancer clinical trials.

This Randomized, Double Blind, Clinical Trial will address the following objectives:

1. Identify distribution of SFN and its metabolites and HDAC inhibition following supplementation with an SFN-rich broccoli sprout extract in subjects at risk for prostate cancer (Primary Endpoints)
2. Investigate the effects of supplementation with an SFN-rich broccoli sprout extract on DNA methylation status and proliferation markers in a pre-biopsy setting (secondary analysis)

The effects of short-term supplementation with an SFN-rich broccoli sprout extract on benign epithelial tissue will be studied in men characterized as being at risk for prostate cancer in a randomized, placebo-controlled trial. Men scheduled for prostate biopsy will be recruited into the trial.

Following successful completion of the consent, two 10 mL blood specimens for study analyses, a 4 mL specimen for total bilirubin assessment will be drawn and the subject will provide a urine sample. The study coordinator will explain the Diet History questionnaires (DHQ) and administer the risk factor and adverse event (AE) questionnaires in order to obtain data on potential confounding dietary variables and gain subjects' baseline symptoms.

The study coordinator will provide the subject with a month' supply of either an SFN-rich broccoli sprout extract (BSE) capsule which consist of 200µmol of sulforaphane (SFN) or matching placebo, as dispensed by the Research Pharmacy. The matching placebo for the BSE consists of a gelatin capsule containing microcrystalline cellulose.

Around every 2 weeks, study coordinator will call to complete AE reporting and any changes in medications or supplements and complete brief cruciferous vegetable intake checklist. Subjects will return any unused study "drug" to the study coordinator at the time of biopsy (or at the 4 week visit if subject's prostate biopsy is delayed).

Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation

Collection of blood and urine specimens occurred at pre-intervention and post-intervention. Change = post-intervention level minus pre-intervention level

In subjects at risk for prostate cancer, presence of SFN was analyzed in plasma. Collection of blood specimens occurred at pre-intervention and post-intervention. The Change = post-intervention level minus pre-intervention level

Ki67 is a biomarker of disease progression. Immunohistochemical (IHC) analysis of Ki67 was performed using research only prostate biopsy specimens collected post-intervention at the time of the clinically-indicated prostate biopsy.

Immunohistochemical (IHC) analysis of HDAC6 expression using research-only prostate biopsy tissue collected post-intervention at the time of the clinically-indicated prostate biopsy. A modified Histo-score (H-score) was calculated, which involved semiquantitative assessment of both staining intensity (graded as 1-3 with 1 representing weak staining, 2 moderate, and 3 strong) and percentage of positive cells. H-score ranged from 0 to 300 with 300 the strongest expression.

Oregon State University

OHSU Knight Cancer Institute

Portland VA Medical Center

Staff Scientist

Subjects in this group were administered with broccoli sprout extract.

Supplement

Subjects in this group were administered with placebo.

Four weeks broccoli sprout extract (BSE) capsules: 200µmol of sulforaphane (SFN) daily, 2 capsules (1 capsule B.I.D.) daily

Broccoli Sprout Extract Capsules

Four weeks placebo capsules: 2 capsules (1 capsule B.I.D.) daily

Dietary Supplement: Gelatin capsule containing microcrystalline cellulose

Placebo Capsules

Race (NIH/OMB)

United States

Dr.Jackilen Shannon

Not all subjects had urine samples for analysis, therefore, the total number of subjects in this urine analysis is different from total number of enrolled subjects.

Change of Total Urine SFN (Sulforaphane) Metabolites

We missed blood samples from some subjects, therefore, total number of subjects analyzed for the plasma-based analysis is different from the number of total enrolled subjects.

Change of Total Plasma SFN (Sulforaphane) Metabolites Level

Some subjects did not have post-intervention prostate tissue that can be used for IHC analysis, therefore, the overall number of participants analyzed for IHC analysis is different from the total enrolled subjects.

Percentage of Ki67 Positive Cells up to 8 Weeks Post-randomization

Expression of Histone Deacetylase 6 (HDAC6)

Recurrence

Disease Attributes

Sulforaphane given 200μmol (total daily) orally in four 50μmol capsules taken once daily from Week 1 Day 1 to Week 20 Day 7. On days when clinic visits are required patient must wait to take that day's dose until instructed to do so in clinic.

Laboratory biomarker analysis

Pharmacological study

Joshi J Alumkal, MD

This phase II trial studies how well sulforaphane works in treating patients with recurrent prostate cancer. Sulforaphane may prevent or slow the growth of certain cancers.

PRIMARY OBJECTIVES:

I. To determine the proportion of patients who achieve a 50% decline in prostate-specific antigen (PSA) levels within 20 weeks of sulforaphane treatment.

SECONDARY OBJECTIVES:

I. To determine the percentage change in PSA from baseline to the final measured value at the end of study as well as the maximal PSA decline that occurs while on study for each subject.

II. To determine the proportion of patients whose PSA has not doubled after full 20 weeks of sulforaphane treatment.

III. To determine the safety profile of sulforaphane. IV. To determine the pharmacokinetics (PK) of sulforaphane and its metabolites in blood.

V. To determine the effect of sulforaphane supplementation on target pharmacodynamic (PD) modulation in peripheral blood cells.

VI. To assess the effect of Glutathione-S-Transferase Mu 1 (GSTM1) genotype on sulforaphane PK, PD.

VII. To collect frozen serum for future analysis of correlative biomarkers.

OUTLINE:

Patients receive sulforaphane orally (PO) once daily for 20 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 14-30 days and every 6 months for 12 months.

Sulforaphane in Treating Patients With Recurrent Prostate Cancer

The Effects of Sulforaphane in Patients With Biochemical Recurrence of Prostate Cancer

To determine the proportion of patients who achieve a decline in PSA levels while receiving sulforaphane treatment. as a measure of anti-tumor activity in men with recurrent prostate cancer.

To determine the percentage change in PSA from baseline to the final measured value at the end of study.

Toxicities will be graded based on the NIH Cancer Therapy Evaluation Program (CTEP) Common Toxicity Criteria of Adverse Events Version 4.0 (http://ctep.cancer.gov). All adverse events of any grade (for example, abnormal laboratory values, etc.) deemed clinically significant by the investigator will be recorded as a measure of the safety profile of sulforaphane

The Wayne D. Kuni and Joan E. Kuni Foundation

Sulforaphane given 200μmol (total daily) orally in four 50μmol capsules taken once daily from Week 1 Day 1 to Week 20 Day 7. On days when clinic visits are required patient must wait to take that day's dose until instructed to do so in clinic

Sulpforaphane

Joshi Alumkal, MD

Proportion of Patients Who Achieve a 50% Decline in Prostate-Specific Antigen (PSA) Levels

Percent Change in PSA From Baseline to Final Measured Value at End of Study

Minimum Percent Change in PSA (i.e., the Smallest Increase for Those With Increased PSA and the Greatest Decline for Those With Decreased PSA)

Proportion of Patients Whose PSA Levels Have Not Doubled

Incidence of Grade 3 or Higher Treatment Related Toxicity

Half-life of Sulforaphane (SFN) in Blood

Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Null Genotype

Half-life of SFN in Blood Among Patients With Glutathione-S-Transferase Mu 1 (GSTM1) Intact Genotype

Allin capsules (x2) and Sulforaphane capsules (x2) once daily for 4 weeks

Allin capsules (x2) and placebo capsules (x2) once daily for 4 weeks

Sulforaphane capsules (x2) and placebo capsules (x2) once daily for 4 weeks

Placebo capsules (x4) once daily for 4 weeks

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers	NCT03232138	Lung Cancer	Sulforaphane Placebo	55 Years - 75 Years	University of Pittsburgh
Broccoli Sprout Intervention in Qidong, P.R. China	NCT01437501	Environmental C...	Broccoli Sprout... placebo beverag...	21 Years - 65 Years	Johns Hopkins Bloomberg School of Public Health
Protective Effects of the Nutritional Supplement Sulforaphane on Doxorubicin-Associated Cardiac Dysfunction	NCT03934905	Anthracycline R...	sulforaphane Placebo Oral Ta...	18 Years - 89 Years	Texas Tech University Health Sciences Center
Protective Effects of the Nutritional Supplement Sulforaphane on Doxorubicin-Associated Cardiac Dysfunction	NCT03934905	Anthracycline R...	sulforaphane Placebo Oral Ta...	18 Years - 89 Years	Texas Tech University Health Sciences Center
Pilot Study Evaluating Broccoli Sprouts in Advanced Pancreatic Cancer [POUDER Trial]	NCT01879878	Pancreatic Duct...	Verum, broccoli... placebo	18 Years -	Heidelberg University
Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation	NCT01265953	Prostate Cancer...	SFN-rich brocco... Gelatin capsule...	21 Years -	Portland VA Medical Center
Sulforaphane in Treating Patients With Recurrent Prostate Cancer	NCT01228084	Adenocarcinoma ... Recurrent Prost...	Sulforaphane Laboratory biom... Pharmacological...	18 Years -	OHSU Knight Cancer Institute
Broccoli Sprout Intervention in Qidong, P.R. China	NCT01437501	Environmental C...	Broccoli Sprout... placebo beverag...	21 Years - 65 Years	Johns Hopkins Bloomberg School of Public Health
Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers	NCT03232138	Lung Cancer	Sulforaphane Placebo	55 Years - 75 Years	University of Pittsburgh
Accumulation of Dietary Bioactives and Prostate Cancer	NCT04046653	Prostate Cancer	Allin Sulforaphane Placebo	18 Years - 80 Years	Quadram Institute Bioscience
Broccoli Sprout Intervention in Qidong, P.R. China	NCT01437501	Environmental C...	Broccoli Sprout... placebo beverag...	21 Years - 65 Years	Johns Hopkins Bloomberg School of Public Health
Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers	NCT03232138	Lung Cancer	Sulforaphane Placebo	55 Years - 75 Years	University of Pittsburgh

Spots Global Cancer Trial Database for sulforaphane

Every month we try and update this database with for sulforaphane cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.