Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers

November 21, 2024 updated by: Jian-Min Yuan, MD

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
43

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

55 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Man or woman 55-75 years of age.
  2. Patients with normal endobronchial biopsy findings or pre-cancerous lesions at baseline will be eligible for the study. Pre-cancerous lesions include (a) reserve cell hyperplasia, (b) squamous metaplasia, (c) mild dysplasia, (d) moderate dysplasia, and (e) severe dysplasia.
  3. A former smoker who has a history of smoking with ≥30 pack-years, quits smoking within the past 10 years, and has ≥1 year sustained abstinence from smoking.
  4. Female subjects must be of non-child bearing potential or must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication) if of childbearing potential.
  5. Male and female subjects of childbearing potential must be willing to use adequate barrier methods of contraception from the time starting with the screening visit through 30 days after the last dose of study therapy.
  6. Abstinence is acceptable if this is the established and preferred contraception for the subject.

  7. Generally healthy with liver enzyme and blood count values within the ranges shown below on the blood sample drawn at the baseline screening visit. Specifically:

    White blood cells ≥ 3,000/mL Total bilirubin ≤ 1.5 x ULN (upper limits of normal) AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN BUN and serum creatinine ≤ 1.5 x ULN Serum pregnancy test Negative

  8. The presence of airflow obstruction on spirometry (GOLD II or greater, Forced Expiratory Volume in the first second (FEV1) <80%) Chronic Obstructive Pulmonary Disease (COPD); and/or any emphysema on CT scan.
  9. Participants must have a Southwest Oncology Group (SWOG) performance status of 0-2
  10. Participants must be able and willing to undergo a bronchoscopy before and after treatment for 12 months.
  11. Patients must be fully informed of the investigational nature of this study and must sign an informed consent in accordance within institutional and regulatory guidelines.

Exclusion Criteria:

  1. Carcinoma in situ or invasive cancer on baseline endobronchial biopsy.
  2. A malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
  3. Severe lung disease or inability to undergo two bronchoscopies.
  4. Had pneumonia or acute bronchitis for at least 2 weeks prior to enrollment.
  5. Cardiac dysrhythmia that is potentially life-threatening, such as ventricular tachycardia, multifocal premature ventricular contractions or supraventricular tachycardias with a rapid ventricular response. Well-controlled atrial fibrillation or rare (< 2 minutes) premature ventricular contractions are not exclusionary.
  6. Evidence of clinically active coronary artery disease, including myocardial infarction within 6 weeks, chest pain, or congestive heart failure, or any serious medical condition which would preclude a patient from undergoing a bronchoscopy or would jeopardize the goals of the study.
  7. Hypoxemia (less than 90% saturation with supplemental oxygen).
  8. Prior chemotherapy or thoracic radiation within the past 5 years.
  9. Woman who is pregnant or plan to be pregnant in next 12 months, or is breast feeding or plan to begin breast feeding in next 12 months.
  10. Life expectancy of < 12 months.
  11. Have a history of irritable bowel disease such as Crohn's disease and ulcerative colitis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sulforaphane (Study Drug)
Sulforaphane four tablets 2 times per day with breakfast and dinner each dose contains approximately 120 micromole of Sulforaphane
Dietary supplement: Sulforaphane
Sulforaphane (SF) is a naturally occurring substance (phytochemical) found in cruciferous vegetables.
Other Names:
  • Avmacol®
Placebo Comparator: Placebo
Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner
Drug: Placebo
Inactive ingredients

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Bronchial Dysplasia Index at 12 Months
Time Frame: 12 months
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. All bronchial biopsies were formalin fixed, paraffin embedded, and H&E stained for subsequent morphologic evaluation and classification defined by the World Health Organization The scale to score the biopsy: 1= normal; 2= reserve cell hyperplasia; 3 = squamous metaplasia; 4 = mild dysplasia; 5 = moderate dysplasia; 6 = severe dysplasia; 7 = carcinoma in situ; and 8 = invasive carcinoma. The higher the score the worse the possible outcome.
12 months
Cell Proliferation Marker Ki-67
Time Frame: 12 months
The primary outcome focuses on the changes of bronchial dysplasia index with cell proliferation marker Ki-67. The determination if a daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial dysplasia index, cell proliferation marker Ki-67. Besides the inhibition of tumor incidence and multiplicity, the use of sulforaphane can inhibit cellular proliferation markers such as Ki-67 and induction of apoptosis hallmarks of tumorigenesis. Ki-67 will be quantified as % positive cells in two slides of each tissue block. First, we calculate the average values of each of the 3 IHC markers over 6 tissue blocks within each bronchoscopy per patient separately for pre- and post-treatment. The primary analysis for these continuous measures will be a linear regression predicting post-treatment score by treatment group, controlling for pre-treatment score.
12 months
Apoptosis Marker TUNEL
Time Frame: 12 months
The determination if a daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial dysplasia index, in apoptosis marker TUNEL in bronchial biopsies in former smokers at high risk for lung cancer. TUNEL will be quantified as % positive cells in two slides of each tissue block. First, we calculate the average values of each of the 3 IHC markers over 6 tissue blocks within each bronchoscopy per patient separately for pre- and post-treatment. The primary analysis for these continuous measures will be a linear regression predicting post-treatment score by treatment group, controlling for pre-treatment score.
12 months
Apoptosis Marker Caspase-3
Time Frame: 12 months
The determination if a daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial dysplasia index, in apoptosis marker Caspase-3 in bronchial biopsies in former smokers at high risk for lung cancer. Caspase-3 will be quantified as % positive cells in two slides of each tissue block. First, we calculate the average values of each of the 3 IHC markers over 6 tissue blocks within each bronchoscopy per patient separately for pre- and post-treatment. The primary analysis for these continuous measures will be a linear regression predicting post-treatment score by treatment group, controlling for pre-treatment score.
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Upregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples
Time Frame: 12 Months
Gene set variation analysis (GSVA) algorithm was used to calculate gene set enrichment scores in bronchial brushing samples. If a gene is upregulated in lung cancer (LC) tissue, the inhibitory effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against LC.
12 Months
Downregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples
Time Frame: 12 months
Gene set variation analysis (GSVA) algorithm was used to calculate gene set enrichment scores in bronchial brushing samples. If a gene is downregulated in LC, the enhancing effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against LC.
12 months
Upregulated Genes Associated With Lung Pre-Malignant Lesions (PML) in Bronchial Brushing Samples
Time Frame: 12 months
GSVA algorithm was used to calculate gene set enrichment scores in bronchial brushing samples. If a gene is upregulated in lung pre-malignant lesions (PML), the inhibitory effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against PML.
12 months
Downregulated Genes Associated With Lung Pre-malignant Lesions (PML) in Bronchial Brushing Samples
Time Frame: 12 months
GSVA algorithm was used to calculate gene set enrichment scores in bronchial brushing samples. If a gene is downregulated in PML, the enhancing effect of sulforaphane (SFN) treatment on such genes also suggests a protective effect against PML.
12 months
Upregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples
Time Frame: 12 months
Similarly, GSVA algorithm was used to calculate gene set enrichment scores in nasal brushing samples. If a gene is upregulated in lung cancer (LC), the inhibitory effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against LC.
12 months
Downregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples
Time Frame: 12 months
GSVA algorithm was used to calculate gene set enrichment scores in nasal brushing samples. If a gene is downregulated in lung cancer (LC), the enhancing effect of sulforaphane (SFN) treatment on such genes also suggests a protective effect against LC.
12 months
Upregulated Genes Associated With Risk of Lung Pre-malignant Lesions Cancer (PML) in Nasal Brushing Samples
Time Frame: 12 months
GSVA algorithm was used to calculate gene set enrichment scores in nasal brushing samples. If a gene is upregulated in PML. the inhibitory effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against PML risk.
12 months
Downregulated Genes Associated With Risk of Lung Pre-malignant Lesions (PML) in Nasal Brushing Samples
Time Frame: 12 months
Similarly, GSVA algorithm was used to calculate gene set enrichment scores in nasal brushing samples. If a gene is downregulated in PML, the overexpression effect of sulforaphane (SFN) treatment on such genes suggests a protective effect against PML
12 months
Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0
Time Frame: 12 Months
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). The severity is calculated by five grades: 1=mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death. Events are assigned to categories of unrelated, possibly elated, probably related, and related.
12 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jian-Min Yuan, MD

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jian-Min Yuan, MD, PhD, Univesity of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 25, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 17, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 17, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 21, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 26, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 27, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 21, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY19040278
  • R01CA213123 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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