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

Condition(s) targeted: Lung Cancer

Intervention: budesonide (Drug); laboratory biomarker analysis (Procedure)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Giulia Veronesi, MD, Study Chair, Affiliation: European Institute of Oncology
Scott M. Lippman, MD, FACP, Affiliation: M.D. Anderson Cancer Center

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.

Official title: 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

Study design: Prevention, Randomized, Double-Blind, Placebo Control

Primary outcome: Shrinkage of lung nodules in a person-specific analysis by RECIST criteria

Secondary outcome:

Lesion-specific analysis by measuring average change in size of the target lesions or in the number of lesions

Bi-dimensional measurement of lesions compared by RECIST and WHO criteria

Three-dimensional measurement of lung nodules compared by RECIST and WHO criteria

Tumoral markers in sputum and plasma compared among the treated group and control group before and after treatment

Modulation of ultrasensitive C-reactive protein (CRP)

Treatment-related toxicity as measured by NCI CTCAE v3.0

Safety as measured by NCI CTCAE v3.0

Effect of the treatment on chronic obstructive pulmonary disease (COPD) as measured by FEV1, FEF 25/75, forced vital capacity, DLCO, and the Medical Research Council questionnaire before and after treatment

Comparison between low dose CT scan and pulmonary function test (PFT) evaluation of emphysema

Detailed description: OBJECTIVES:

Primary

- Evaluate the effect, in terms of size and number reduction of 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.

Minimum age: 50 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Current smokers or former smokers that have stopped within the last 15 years

- Smoking history ≥ 20 pack/years

- Persistence of lung nodules detected at low-dose CT scan for a second year (within the

COSMOS screening program) with one of the following characteristics:

- Longest diameter between 4 and 5 mm

- Nodules may be both stable or grown from the previous year

- Longest diameter between 5. 1 mm and 8 mm

- Nodules may be both stable or grown from the previous year (if grown,

doubling time should be more than 1 year)

- Longest diameter > 8 mm

- Nodule should have grown with a doubling time between 1 and 5 years

- No more than 6 lung nodules and no suspicion of chronic granulomatous disease

- No lung nodules with clearly benign morphological features on CT scan (i. e.,

homogenous calcification or solid nodules with regular and round or polygonal margins and distance from the pleura ≤ 1cm)

PATIENT CHARACTERISTICS:

- ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%

- WBC > 3,000/mm³

- Absolute neutrophil count > 1,500/mm³

- Platelet count > 100,000/mm³

- Bilirubin < 1. 5 times upper limit of normal (ULN)

- AST/ALT < 1. 5 times ULN

- Creatinine < 1. 5 times ULN

- Not pregnant or nursing

- Fertile participants must use effective contraception

- Negative pregnancy test

- No HIV or other immunodeficiencies

- No other malignant disease within the last 5 years, except cervical carcinoma in situ

or nonmelanoma skin cancer

- No contraindication to the use of inhaled corticosteroids

- No history of allergy to compounds of similar chemical or biological composition to

corticosteroids

- No uncontrolled intercurrent illness including, but not limited to:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Serious cardiac arrhythmia

- Lung tuberculosis or other infection of the airways

- Psychiatric illness or social situations that would limit study compliance

PRIOR CONCURRENT THERAPY:

- At least 3 months since other prior investigational agents

- No prior or concurrent regular use, defined as a total of 3 months cumulative use

within the last 12 months, of oral or inhaled corticosteroids

European Institute of Oncology, Milan 20141, Italy

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: April 2006
Last updated: May 23, 2008