Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers

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: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Dietary supplement: Sulforaphane; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Bronchial dysplasia index	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.	12 months
Cell proliferation marker Ki-67	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.	12 months
Apoptosis markers including caspase-3 and TUNEL	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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gene Expression	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.	12 Months
Bronchial Pre-malignant lesions	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.	12 months
Gene Expression Nasal Epithelia	To explore if daily oral dose of 120 micromole SF can modulate the similar changes of the gene expression markers in nasal epithelia.	12 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	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).	12 Months

Collaborators and Investigators

• Sponsor: Jian-Min Yuan, MD
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jian-Min Yuan, MD, PhD, Univesity of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2018
• Primary Completion (Actual): February 17, 2023
• Study Completion (Actual): February 17, 2023

Study Registration Dates

• First Submitted: July 21, 2017
• First Submitted That Met QC Criteria: July 26, 2017
• First Posted (Actual): July 27, 2017

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Sulforaphane; Chemoprevention; Former Smokers
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Anticarcinogenic Agents; Sulforaphane
• Other Study ID Numbers: HCC 16-135; 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