<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03232138</url>
  </required_header>
  <id_info>
    <org_study_id>HCC 16-135</org_study_id>
    <secondary_id>R01CA213123</secondary_id>
    <nct_id>NCT03232138</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers</brief_title>
  <official_title>Randomized Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jian-Min Yuan, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study involves taking an experimental anti-cancer dietary supplement called&#xD;
      Sulforaphane (SF) or a placebo (product without any supplement content) over a period of&#xD;
      twelve months in order to determine if it is a useful dietary supplement for prevention of&#xD;
      lung cancer in humans.&#xD;
&#xD;
      The main goals of this research study are:&#xD;
&#xD;
        1. To learn about the effects of giving Sulforaphane (SF) to former smokers who are still&#xD;
           at high risk of developing cancer due to their smoking history and whether or not their&#xD;
           condition improves, stays the same or becomes worse after Sulforaphane (SF) is given.&#xD;
&#xD;
        2. To learn whether Sulforaphane (SF) might reverse some of the lung cell changes&#xD;
           associated with future development of lung cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 25, 2018</start_date>
  <completion_date type="Anticipated">October 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Bronchial dysplasia index</measure>
    <time_frame>12 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cell proliferation marker Ki-67</measure>
    <time_frame>12 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apoptosis markers including caspase-3 and TUNEL</measure>
    <time_frame>12 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gene Expression</measure>
    <time_frame>12 Months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bronchial Pre-malignant lesions</measure>
    <time_frame>12 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene Expression Nasal Epithelia</measure>
    <time_frame>12 months</time_frame>
    <description>To explore if daily oral dose of 120 micromole SF can modulate the similar changes of the gene expression markers in nasal epithelia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>12 Months</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">67</enrollment>
  <condition>Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Sulforaphane (Study Drug)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sulforaphane four tablets 2 times per day with breakfast and dinner each dose contains approximately 120 micromole of Sulforaphane</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Sulforaphane</intervention_name>
    <description>Sulforaphane (SF) is a naturally occurring substance (phytochemical) found in cruciferous vegetables.</description>
    <arm_group_label>Sulforaphane (Study Drug)</arm_group_label>
    <other_name>Avmacol®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Inactive ingredients</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Man or woman 55-75 years of age.&#xD;
&#xD;
          2. Patients with normal endobronchial biopsy findings or pre-cancerous lesions at&#xD;
             baseline will be eligible for the study. Pre-cancerous lesions include (a) reserve&#xD;
             cell hyperplasia, (b) squamous metaplasia, (c) mild dysplasia, (d) moderate dysplasia,&#xD;
             and (e) severe dysplasia.&#xD;
&#xD;
          3. A former smoker who has a history of smoking with ≥30 pack-years, quits smoking within&#xD;
             the past 10 years, and has ≥1 year sustained abstinence from smoking.&#xD;
&#xD;
          4. Female subjects must be of non-child bearing potential or must have a negative serum&#xD;
             pregnancy test at screening (within 72 hours of first dose of study medication) if of&#xD;
             childbearing potential.&#xD;
&#xD;
          5. Male and female subjects of childbearing potential must be willing to use adequate&#xD;
             barrier methods of contraception from the time starting with the screening visit&#xD;
             through 30 days after the last dose of study therapy.&#xD;
&#xD;
          6. Abstinence is acceptable if this is the established and preferred contraception for&#xD;
             the subject.&#xD;
&#xD;
          7. Generally healthy with liver enzyme and blood count values within the ranges shown&#xD;
             below on the blood sample drawn at the baseline screening visit. Specifically:&#xD;
&#xD;
             White blood cells ≥ 3,000/mL Total bilirubin ≤ 1.5 x ULN (upper limits of normal) AST&#xD;
             (SGOT)/ALT (SGPT) ≤ 2.5 x ULN BUN and serum creatinine ≤ 1.5 x ULN Serum pregnancy&#xD;
             test Negative&#xD;
&#xD;
          8. The presence of airflow obstruction on spirometry (GOLD II or greater, Forced&#xD;
             Expiratory Volume in the first second (FEV1) &lt;80%) Chronic Obstructive Pulmonary&#xD;
             Disease (COPD); and/or any emphysema on CT scan.&#xD;
&#xD;
          9. Participants must have a Southwest Oncology Group (SWOG) performance status of 0-2&#xD;
&#xD;
         10. Participants must be able and willing to undergo a bronchoscopy before and after&#xD;
             treatment for 12 months.&#xD;
&#xD;
         11. Patients must be fully informed of the investigational nature of this study and must&#xD;
             sign an informed consent in accordance within institutional and regulatory guidelines.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Carcinoma in situ or invasive cancer on baseline endobronchial biopsy.&#xD;
&#xD;
          2. A malignancy except for adequately treated basal cell or squamous cell skin cancer or&#xD;
             in situ cervical cancer.&#xD;
&#xD;
          3. Severe lung disease or inability to undergo two bronchoscopies.&#xD;
&#xD;
          4. Had pneumonia or acute bronchitis for at least 2 weeks prior to enrollment.&#xD;
&#xD;
          5. Cardiac dysrhythmia that is potentially life-threatening, such as ventricular&#xD;
             tachycardia, multifocal premature ventricular contractions or supraventricular&#xD;
             tachycardias with a rapid ventricular response. Well-controlled atrial fibrillation or&#xD;
             rare (&lt; 2 minutes) premature ventricular contractions are not exclusionary.&#xD;
&#xD;
          6. Evidence of clinically active coronary artery disease, including myocardial infarction&#xD;
             within 6 weeks, chest pain, or congestive heart failure, or any serious medical&#xD;
             condition which would preclude a patient from undergoing a bronchoscopy or would&#xD;
             jeopardize the goals of the study.&#xD;
&#xD;
          7. Hypoxemia (less than 90% saturation with supplemental oxygen).&#xD;
&#xD;
          8. Prior chemotherapy or thoracic radiation within the past 5 years.&#xD;
&#xD;
          9. Woman who is pregnant or plan to be pregnant in next 12 months, or is breast feeding&#xD;
             or plan to begin breast feeding in next 12 months.&#xD;
&#xD;
         10. Life expectancy of &lt; 12 months.&#xD;
&#xD;
         11. Have a history of irritable bowel disease such as Crohn's disease and ulcerative&#xD;
             colitis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jian-Min Yuan, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Univesity of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 21, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2017</study_first_posted>
  <last_update_submitted>September 28, 2022</last_update_submitted>
  <last_update_submitted_qc>September 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Jian-Min Yuan, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Sulforaphane</keyword>
  <keyword>Chemoprevention</keyword>
  <keyword>Former Smokers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sulforaphane</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03232138
org study id: HCC 16-135
secondary id: R01CA213123
nct id: NCT03232138
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double Blind
measure: Bronchial dysplasia index
time frame: 12 months
description: 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.
measure: Cell proliferation marker Ki-67
time frame: 12 months
description: 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.
measure: Apoptosis markers including caspase-3 and TUNEL
time frame: 12 months
description: 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.
measure: Gene Expression
time frame: 12 Months
description: 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.
measure: Bronchial Pre-malignant lesions
time frame: 12 months
description: 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.
measure: Gene Expression Nasal Epithelia
time frame: 12 months
description: To explore if daily oral dose of 120 micromole SF can modulate the similar changes of the gene expression markers in nasal epithelia.
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: 12 Months
description: 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).
arm group label: Sulforaphane (Study Drug)
arm group type: Experimental
description: Sulforaphane four tablets 2 times per day with breakfast and dinner each dose contains approximately 120 micromole of Sulforaphane
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo (containing no active drug) four tablets 2 times per day with breakfast and dinner
intervention type: Dietary Supplement
intervention name: Sulforaphane
description: Sulforaphane (SF) is a naturally occurring substance (phytochemical) found in cruciferous vegetables.
arm group label: Sulforaphane (Study Drug)
other name: Avmacol®
intervention type: Drug
intervention name: Placebo
description: Inactive ingredients
arm group label: Placebo
criteria: 
gender: All
minimum age: 55 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jian-Min Yuan, MD, PhD
role: Principal Investigator
affiliation: Univesity of Pittsburgh
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Jian-Min Yuan, MD
investigator title: Principal Investigator
mesh term: Lung Neoplasms
mesh term: Sulforaphane
sharing ipd: No