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

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of budesonide may keep lung cancer from forming in patients with lung nodules. PURPOSE: This randomized phase II trial is studying how well inhalation budesonide works in treating patients with lung nodules who are at high risk of lung cancer.

Detailed Description
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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.

Official Title
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Randomized Phase II Trial of Budesonide Turbuhaler® 800 Micrograms/Twice Daily Versus Placebo in High-Risk Population With Undetermined Lung Nodules Detected at Screening Low Dose CT Scan

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Budesonide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I: Budesonide<br>Inhaled Budesonide 800 ug twice daily for 1 year | Drug: Budesonide<br>* Inhaled Budesonide 800 micrograms (ug) twice daily for one year.<br>* Other names: Rhinocort aqua;|
| Placebo Comparator: Arm II: Placebo<br>Inhaled placebo twice daily for 1 year | Other: Placebo<br>* Inhaled placebo twice daily for one year.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number CT- Detected Lung Nodules by Participant | Lung nodules (nodule characteristics) in a person-specific analysis by Response Evaluation Criteria In Solid Tumors (RECIST) criteria using Computed Tomography (CT) detection: Persistent lung nodules detected at CT scan from previous year with 1 of 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& 8mm. Nodules may be stable or grown from the previous year. If grown, doubling time should be >1 year; longest diameter > 8 mm with negative positron positron emission tomography (PET) scan, negative CT enhancement. Nodule should have grown with 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. Participants followed from baseline to 3 Years, follow up CT assessment planned at 12 months. | Baseline assessment | 
| Size of CT- Detected Lung Nodules by Participant | Lung nodules (nodule characteristics) in a person-specific analysis by Response Evaluation Criteria In Solid Tumors (RECIST) criteria using Computed Tomography (CT) detection. Nodule type categorized as: Nonsolid, Partially Solid, or Solid. Persistent lung nodules detected at CT scan from previous year with 1 of 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& 8mm. Nodules may be stable or grown from the previous year. If grown, doubling time should be >1 year; longest diameter > 8 mm with negative positron positron emission tomography (PET) scan, negative CT enhancement. Nodule should have grown with 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 | Baseline assessment | 
| Number of Participant Overall Responses as Measured by RECIST Criteria at 12 Months | For single nodules >5 mm, clinical meaningful shrinkage of 30% or > longest diameter (LD) considered treatment success after 1 year treatment; for <5 mm, complete disappearance considered treatment success. Multiple lesions success is complete response (CR) or partial response (PR) according to RECIST while failure when progression disease (PD) or stable disease (SD). CR: disappearance all target & non target lesions + no appearance new lesions; PR: CR for target lesions+incomplete/SD for non target lesions+no new lesions or PR (i.e., 30%<sum LD target lesions) for target lesions + no PD for non target lesions + no appearance of new lesions; PD: PD (at least 20% > sum LD of target lesions) for target lesions irrespective of response of non target lesions or PD for non target lesions irrespective of response for target lesions/or appearance new lesions irrespective of response of target/or non target lesions; SD: neither sufficient shrinkage for PR nor increase for PD. | 12 Months | 
| Participant Overall Response (by Tumor Type Subsolid or Solid Tumor) as Measured by RECIST Criteria at 12 Months | Number of participants with response according to RECIST criteria. For single nodules > 5 mm, clinical meaningful shrinkage of 30% or > of longest diameter (LD) considered treatment success after 1 year of treatment. For single nodules with LD <5 mm, complete disappearance considered treatment success. In case of multiple lesions success of treatment is when complete response (CR) or partial response (PR) occurs according to RECIST criteria. | 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Small cell lung cancer, Non-small cell lung cancer, Budesonide, Entocort EC, Pulmicort Respules, Rhinocort aqua, Aerosol budesonide treatment, Smoking