Clinical trial NCT03232138: Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers
Official title: Randomized Clinical Trial of Lung Cancer Chemoprevention With Sulforaphane in Former Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: Sulforaphane
Chemoprevention
Former Smokers
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-07-27
Enrollment: 43
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Bronchial Dysplasia Index at 12 Months
timeFrame: 12 months
measure: Cell Proliferation Marker Ki-67
timeFrame: 12 months
measure: Apoptosis Marker TUNEL
timeFrame: 12 months
measure: Apoptosis Marker Caspase-3
timeFrame: 12 months
Secondary outcomes:
measure: Upregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples
timeFrame: 12 Months
measure: Downregulated Genes Associated With Lung Cancer Risk in Bronchial Brushing Samples
timeFrame: 12 months
measure: Upregulated Genes Associated With Lung Pre-Malignant Lesions (PML) in Bronchial Brushing Samples
timeFrame: 12 months
measure: Downregulated Genes Associated With Lung Pre-malignant Lesions (PML) in Bronchial Brushing Samples
timeFrame: 12 months
measure: Upregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples
timeFrame: 12 months
measure: Downregulated Genes Associated With Risk of Lung Cancer in Nasal Brushing Samples
timeFrame: 12 months
measure: Upregulated Genes Associated With Risk of Lung Pre-malignant Lesions Cancer (PML) in Nasal Brushing Samples
timeFrame: 12 months
measure: Downregulated Genes Associated With Risk of Lung Pre-malignant Lesions (PML) in Nasal Brushing Samples
timeFrame: 12 months
measure: Overall Number of Adverse Events That Occurred in the Study Population as Assessed by CTCAE v4.0
timeFrame: 12 Months
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
Study officials:
affiliation: Univesity of Pittsburgh
name: Jian-Min Yuan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: