This randomized phase II trial is studying inositol to see how well it works compared with a placebo in preventing lung cancer in current or former smokers with bronchial dysplasia. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of inositol may prevent lung cancer. It is not yet known whether inositol is more effective than a placebo in preventing lung cancer in smokers with bronchial dysplasia.
PRIMARY OBJECTIVES: I. To evaluate the efficacy of myo-inositol (inositol) 9 grams by mouth twice a day for 6 months versus placebo to revert bronchial dysplasia in current/former smokers with or without curatively treated Stage 0/I non-small cell lung cancer. SECONDARY OBJECTIVES: I. To further define the mechanism(s) of action of pharmacological doses of myo-inositol as a lung cancer chemopreventive agent by evaluating changes in: the number of dysplastic lesions, Ki-67, caspase-3, peroxisome proliferator-activated receptor (PPAR) gamma, cyclin D1, cyclin E and vascular endothelial growth factor (VEGF) immunostaining in bronchial biopsies; gene expression analysis of ribonucleic acid (RNA) from bronchial brush cells; and changes in inflammatory biomarkers (C-reactive protein \[CRP\], monocyte chemotactic protein-1 \[MCP-1\], myeloid progenitor inhibitory factor-1 \[MPIF-1\] and L-Selectin) levels in bronchoalveolar lavage (BAL) and plasma before and after treatment. II. To collect additional safety and adverse event profiles of participants enrolled in both intervention arms. III. To establish a biospecimen repository archive for future correlative studies. OUTLINE: Patients are stratified according to smoking status (current vs former), prior lung cancer (yes vs no), and number of dysplastic lesions at baseline (1 vs \> 1). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oral inositol once daily for 2 weeks and then twice daily for up to 6 months in the absence of unacceptable toxicity. ARM II: Patients receive oral placebo once daily for 2 weeks and then twice daily for up to 6 months in the absence of unacceptable toxicity. Patients undergo white light and autofluorescence bronchoscopy with bronchoalveolar lavage, bronchial brushings, and biopsies as well as optical coherence tomography imaging and blood sample collection at baseline and after completion of study treatment. Samples are analyzed for tissue biomarkers (e.g., PPAR gamma, Ki-67, caspase-3, cyclin D1, cyclin E, and VEGF) by immunohistochemistry (IHC); cytokine levels (e.g., CRP, MCP-1, MPIF-1, and L-selectin) by ELISA; and gene expression profiles of RNA by microarray. After completion of study treatment, patients are followed within 30 days.
Study Type
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Mayo Clinic
Rochester, Minnesota, United States
Albuquerque Veterans Administration Medical Center
Albuquerque, New Mexico, United States
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada
Percentage of Participants With Response Determined by Change in the Histologic Grade of Bronchial Dysplasia as Measured by Mucosal Biopsy Samples on Participant-specific Analysis.
The definitions of responses are: Complete response: regression of all dysplastic lesion (DL) found at baseline to lesions that were no worse than hyperplasia and no new DL that were mild dysplasia or worse; Partial response: regression of some but not all of the DL with no new lesions that are mild dysplasia or worse; Progressive disease: progression of one or more sites by two or more grades or new DL that were mild dysplasia or worse; Stable disease: no complete response, partial response or progression.
Time frame: From baseline up to 6 months
Percentage of Participants With Response Determined by Change in the Histologic Grade of Bronchial Dysplasia as Measured by Mucosal Biopsy Samples on Lesion-specific Analysis.
The definitions of responses are: Complete response: the regression of a dysplastic lesion (DL) of any grade to one classified as being hyperplastic/normal; Progressive disease: appearance of lesions that were classified as mild dysplasia or worse; Stable disease: lesions that are not classified as complete response or progressive disease
Time frame: From baseline up to 6 months
Percent Change in the Number of Bronchial Dysplastic Lesions Before and After Treatment
The change in the number of bronchial dysplastic lesions is defined as disappearance or appearance of lesions.
Time frame: From baseline up to 6 months
Mean Percent Change in Ki-67 Expression Level in the Bronchial Biopsies With Dysplasia
Time frame: From baseline up to 6 months
Change in Gene Expression Profiles of RNA in Bronchial Brush Cell Samples as Assessed by Microarray
Time frame: From baseline up to 6 months
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INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
85
Change in Inflammatory Biomarkers Levels (CC-16) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (IL-6) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (CCL-2) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (MPO) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (CC18) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (SFTPD) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (Total Glutathione) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (CC-16) in Plasma Samples as Assessed by ELISA
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (CRP) in Plasma Samples as Assessed by ELISA
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (IL-6) in Plasma Samples as Assessed by ELISA
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (CCL-2) in Plasma Samples as Assessed by ELISA
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (MPO) in Plasma Samples as Assessed by ELISA
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (Nitrotyrosine) in Plasma Samples as Assessed by ELISA
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (CC18) in Plasma Samples as Assessed by ELISA
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months
Change in Inflammatory Biomarkers Levels (SFTPD) in Plasma Samples as Assessed by ELISA
The biomarkers that were examined were: 1) pro-inflammatory proteins: C-reactive protein (CRP, R\&D Systems), interleukin-6 (IL-6, R\&D Systems), and CCL-2 (R\&D Systems); 2) oxidant/antioxidants: myeloperoxidase (MPO, R\&D Systems), nitrotyrosine (Hycult Biotech) and glutathione (Millipore-Calbiochem); and 3) pneumoproteins: Clara cell protein-16 (CC-16, Biovendor), surfactant protein-D (SFTPD, R\&D Systems) and CC18 (R\&D Systems).
Time frame: From baseline up to 6 months