Avmacol for the Prevention of Lung Cancer in Former Smokers
This phase II trial studies how well Avmacol works for the prevention of lung cancer in former smokers. Former smokers remain at high risk of lung cancer even after they quit smoking for many years. Avmacol is a dietary supplement which contains broccoli seed extracts and broccoli sprout extracts. Avmacol may reverse some of the lung cell changes associated with future development of lung cancer.
Inclusion Criteria
- 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
- A former smoker who has a history of smoking with >= 30 pack-years, quits smoking within the past 10 years, and has more than 1 year sustained abstinence from smoking
- Female subjects must be of non-child bearing potential or must have a negative urine pregnancy test at screening (within 72 hours of first dose of study medication) if of childbearing potential
- 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
- Abstinence is acceptable if this is the established and preferred contraception for the subject
- White blood cells >= 3,000/mL (at the baseline screening visit)
- Total bilirubin =< 1.5 x ULN (upper limits of normal) (at the baseline screening visit)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (at the baseline screening visit)
- Blood urea nitrogen (BUN) =< 1.5 x ULN (at the baseline screening visit)
- Serum creatinine =< 1.5 x ULN (at the baseline screening visit)
- The presence of airflow obstruction on spirometry (Global Initiative for Chronic Obstructive Lung Disease (GOLD)[GOLD] I or greater, forced expiratory volume in 1 second [FEV1] < 80%) chronic obstructive pulmonary disease (COPD); and/or any emphysema on computed tomography (CT) scan
- Participants must have a Southwest Oncology Group (SWOG) performance status of 0-2
- Participants must be able and willing to undergo a bronchoscopy before and after treatment for 12 months
- 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
- Carcinoma in situ or invasive cancer on baseline endobronchial biopsy
- A malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
- Severe lung disease or inability to undergo two bronchoscopies
- Had pneumonia or acute bronchitis within the past 2 weeks prior to the date of enrollment (i.e., signing the consent form)
- Had myocardial infarction (MI) or other severe heart diseases such as ventricular tachycardia, multifocal premature ventricular contractions or supraventricular tachycardias with a rapid ventricular response within the past 6 weeks prior to enrollment
- Hypoxemia (less than 90% saturation with supplemental oxygen)
- Prior chemotherapy or thoracic radiation within the past 5 years
- 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
- Life expectancy of < 12 months
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03232138.
PRIMARY OBJECTIVES:
I. To recruit 72 former smokers at high risk of developing lung cancer who will be randomly assigned to either receiving broccoli sprout/broccoli seed extract supplement (Avmacol) or placebo tablets for 12 months.
II. To determine if daily oral dose of 120 micromole sulforaphane (SF) for 12 months can modulate the changes of bronchial dysplasia index, cell proliferation marker Ki-67, and apoptosis markers caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in bronchial biopsies in former smokers at high risk for lung cancer.
SECONDARY OBJECTIVES:
I. To explore if daily oral dose of 120 micromole SF for 12 months can modulate the changes of the lung cancer-related gene expression markers in bronchial epithelia in former smokers at high risk for lung cancer.
II. To explore if daily oral dose of 120 micromole SF for 12 months can modulate the changes of bronchial premalignant lesions-related gene expression markers in former smokers at high risk for lung cancer.
III. To explore if daily oral dose of 120 micromole SF for 12 months can modulate the similar changes of the gene expression markers in nasal epithelia as in the bronchial epithelia identified in Secondary Objectives I and II.
IV. To determine the safety and toxicity of daily oral dose of 120 micromole SF for 12 months in former smokers at high risk for lung cancer.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive Avmacol orally (PO) twice daily (BID) for up to 12 months in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive placebo PO BID for up to 12 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1 month and 1 year.
Trial PhasePhase II
Trial Typeprevention
Lead OrganizationUniversity of Pittsburgh Cancer Institute (UPCI)
Principal InvestigatorJian-Min Yuan
- Primary IDSF-001
- Secondary IDsNCI-2019-07132
- ClinicalTrials.gov IDNCT03232138