Budesonide in Treating Patients With Lung Nodules at High Risk of Developing Lung Cancer

OBJECTIVES:

Primary

• Evaluate the effect, in terms of size and number reduction of computed tomography (CT) scan-detected undetermined lung nodules, in asymptomatic subjects with lung nodules at high-risk for developing lung cancer treated with inhaled budesonide vs placebo.

Secondary

• Compare average modification of nodule size and nodule number due to inhaled budesonide versus placebo.
• Correlate the modulation of biological markers of lung cancer in serum and sputum after treatment with the modification of lung nodules sizes.
• Determine treatment toxicity, side effects, and safety of inhaled budesonide.
• Evaluate the role of CT scans in estimating the grade of respiratory impairment and emphysema.
• Determine the effect of inhaled budesonide on respiratory function before and after treatment.

OUTLINE: This is a randomized, double-blind, placebo controlled study.

Participants are stratified according to gender, smoking habit (current vs former smoker), and nodule characteristics (solid vs semisolid or non-solid). Participants are randomized into 1 of 2 treatment arms.

• Arm I: Subjects receive inhaled budesonide twice daily for 1 year in the absence of unacceptable toxicity.
• Arm II: Subjects receive inhaled placebo twice daily for 1 year in the absence of unacceptable toxicity.

Participants undergo blood and sputum collection periodically during study for biomarker and correlative studies.

After completion of study therapy, subjects are followed at 1 month and continue CT scan screening.

PROJECTED ACCRUAL: A total of 202 patients will be accrued for this study.

Inclusion criteria

• Current smokers or former smokers that have stopped within the last 15 years
• Smoking history > 20 pack/years
• Age > 50 years
• Persistent lung nodules detected at Low dose computed tomography (LDCT) scan from previous year with 1 of the following:- longest diameter between 4&5 mm. Nodules may be stable or grown from the previous year (< 5 mm does not require additional diagnostic follow-up); longest diameter between 5.1 & 8 mm. Nodules may be stable or grown from the previous year. If grown, doubling time should be >1 year; longest diameter > 8 mm with negative PET scan, negative CT enhancement. Nodule should have grown with a doubling time between 1& 5 years; -longest diameter >8mm, non solid or partially solid nodules, stable or grown with doubling time between 1&5 years
• Eastern Cooperative Oncology Group (ECOG) performance status < 1 (Karnofsky >60%)
• Participants must have normal organ and marrow function as defined below: Leukocytes >3,000/mL, absolute neutrophil count greater than 1,500/mL, platelets greater than 100,000/mL, total bilirubin lower than 1.5 * upper normal institutional limits, aspartate aminotransferase (AST or SGOT)/alanine aminotransferase (ALT or SGPT) lower than 1.5 * upper normal institutional limits, creatinine lower than 1.5 * upper normal institutional limits
• Females must be postmenopausal (ie, at least 1 year passed after the last menstruation), surgically sterile, or using acceptable contraceptive measures as judged by the Investigator. (A fertile woman is defined as being of child-bearing potential, from first menstruation to 1 year after last menstruation.). Negative serum beta-HCG for women of childbearing potential will be required at baseline. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

• More than 6 lung nodules (suspect of chronic granulomatous disease)
• Lung nodules with clearly benign morphological features at CT scan (i.e, homogenous calcification, solid nodules with regular and round or polygonal margins and distance from the pleura <1cm)
• Subjects currently suffering from malignant disease or having had malignant disease within the last 5 years except for cervical carcinoma in situ and non melanoma skin cancer
• Regular/chronic use of oral or inhaled corticosteroids; regular use being defined as a total of 3 months cumulative use in the last 12 months
• Use of any other investigational agents at time of enrollment in the study during the three months preceding study enrollment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to corticosteroid
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Any other factor that at the investigator's discretion contraindicates the use of inhaled corticosteroids
• Pregnant or lactating females, or females planning to become pregnant during the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. If needed, a pregnancy test will be performed on serum during baseline lab test
• HIV-positive or other patients with immunodeficiencies should be excluded because of the risk of infections