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Inositol in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia

Primary Purpose

Non-small Cell Lung Cancer, Squamous Lung Dysplasia

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

placebo

inositol

About this trial

This is an interventional prevention trial for Non-small Cell Lung Cancer

Eligibility Criteria

45 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically confirmed bronchial dysplasia in ≥ 1 site AND meets one of the following criteria:
- Current or former smoker with ≥ a 30 pack-year smoking history and no history of lung cancer
- Stage 0 or I non-small cell lung cancer (NSCLC) curatively treated by surgery (local ablation or resection), adjuvant chemotherapy, or radiotherapy with a ≥ 30 pack-year smoking history
  - At least 6 months since prior surgery, adjuvant chemotherapy, or radiotherapy
No current evidence of lung cancer by CT scan
- No non-calcified lung nodules ≥ 10 mm diameter on spiral CT scan unless cancer is ruled out by PET/CT scan or by biopsy
ECOG performance status 0-1
Hemoglobin normal
Leukocyte count ≥ 3,000/mm³
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 1.5 times ULN
ALT and AST ≤ 1.5 times ULN
BUN ≤ 1.5 times ULN
Chloride ≤ 1.5 times ULN
Total CO_2 ≤ 1.5 times ULN
Sodium ≤ 1.5 times ULN
Calcium ≤ 1.5 times ULN
Potassium ≤ 1.5 times ULN
Phosphorus ≤ 1.5 times ULN
Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 30mL/min
Fasting blood glucose normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No cancer within the past 3 years except stage 0 or I NSCLC, nonmelanomatous skin cancer, localized prostate cancer, carcinoma in situ of the cervix, or superficial bladder cancer that was treated > 6 months ago
No concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Severe chronic obstructive pulmonary disease requiring supplemental oxygen
- Uncontrolled hypertension
- Psychiatric illness or social situation that would limit compliance with study requirements
No schizophrenia or bipolar disorder
No diabetes
No requirement for supplemental oxygen (continuous or intermittent)
SaO_2 ≥ 90% on room air
No history of allergic reactions attributed to inositol
No history of allergies to any ingredient in the study agent or placebo
No other concurrent investigational agents
At least 7 days since prior anticoagulant use (e.g., coumadin or heparin)
More than 6 months since prior participation in another chemoprevention clinical trial
No prior pneumonectomy
No prior solid organ transplantation
No concurrent lithium, carbamazepine, or valproate
No concurrent use of other natural health products containing inositol

Sites / Locations

Mayo Clinic in Arizona
Mayo Clinic
Albuquerque Veterans Administration Medical Center
BCCA-Vancouver Cancer Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm I (inositol)

Arm II (placebo)

Arm Description

Patients receive oral inositol once daily for 2 weeks and then twice daily for up to 6 months in the absence of unacceptable toxicity.

Patients receive oral placebo once daily for 2 weeks and then twice daily for up to 6 months in the absence of unacceptable toxicity.

Outcomes

Primary Outcome Measures

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.

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

Secondary Outcome Measures

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.

Mean Percent Change in Ki-67 Expression Level in the Bronchial Biopsies With Dysplasia

Change in Gene Expression Profiles of RNA in Bronchial Brush Cell Samples as Assessed by Microarray

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).

Change in Inflammatory Biomarkers Levels (IL-6) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Change in Inflammatory Biomarkers Levels (CCL-2) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Change in Inflammatory Biomarkers Levels (MPO) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Change in Inflammatory Biomarkers Levels (CC18) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Change in Inflammatory Biomarkers Levels (SFTPD) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Change in Inflammatory Biomarkers Levels (Total Glutathione) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Change in Inflammatory Biomarkers Levels (CC-16) in Plasma Samples as Assessed by ELISA

Change in Inflammatory Biomarkers Levels (CRP) in Plasma Samples as Assessed by ELISA

Change in Inflammatory Biomarkers Levels (IL-6) in Plasma Samples as Assessed by ELISA

Change in Inflammatory Biomarkers Levels (CCL-2) in Plasma Samples as Assessed by ELISA

Change in Inflammatory Biomarkers Levels (MPO) in Plasma Samples as Assessed by ELISA

Change in Inflammatory Biomarkers Levels (Nitrotyrosine) in Plasma Samples as Assessed by ELISA

Change in Inflammatory Biomarkers Levels (CC18) in Plasma Samples as Assessed by ELISA

Change in Inflammatory Biomarkers Levels (SFTPD) in Plasma Samples as Assessed by ELISA

Full Information

NCT ID

NCT00783705

First Posted

October 31, 2008

Last Updated

October 30, 2017

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00783705

Brief Title

Inositol in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia

Official Title

Phase IIb Randomized Comparative Study of the Efficacy and Safety of Myo-inositol Versus Placebo in Smokers With Bronchial Dysplasia

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Completed

Study Start Date

November 2008 (undefined)

Primary Completion Date

May 2014 (Actual)

Study Completion Date

May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-small Cell Lung Cancer, Squamous Lung Dysplasia

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

85 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I (inositol)

Arm Type

Experimental

Arm Description

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 Title

Arm II (placebo)

Arm Type

Experimental

Arm Description

Patients receive oral placebo once daily for 2 weeks and then twice daily for up to 6 months in the absence of unacceptable toxicity.

Intervention Type

Other

Intervention Name(s)

placebo

Other Intervention Name(s)

PLCB

Intervention Description

Given orally

Intervention Type

Drug

Intervention Name(s)

inositol

Other Intervention Name(s)

myo-inositol

Intervention Description

Given orally

Primary Outcome Measure Information:

Title

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.

Description

Time Frame

From baseline up to 6 months

Title

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.

Description

Time Frame

From baseline up to 6 months

Secondary Outcome Measure Information:

Title

Percent Change in the Number of Bronchial Dysplastic Lesions Before and After Treatment

Description

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

Title

Mean Percent Change in Ki-67 Expression Level in the Bronchial Biopsies With Dysplasia

Time Frame

From baseline up to 6 months

Title

Change in Gene Expression Profiles of RNA in Bronchial Brush Cell Samples as Assessed by Microarray

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (CC-16) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (IL-6) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (CCL-2) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (MPO) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (CC18) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (SFTPD) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (Total Glutathione) in Bronchoalveolar Lavage Samples as Assessed by Enzyme-linked Immunoassay (ELISA)

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (CC-16) in Plasma Samples as Assessed by ELISA

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (CRP) in Plasma Samples as Assessed by ELISA

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (IL-6) in Plasma Samples as Assessed by ELISA

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (CCL-2) in Plasma Samples as Assessed by ELISA

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (MPO) in Plasma Samples as Assessed by ELISA

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (Nitrotyrosine) in Plasma Samples as Assessed by ELISA

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (CC18) in Plasma Samples as Assessed by ELISA

Description

Time Frame

From baseline up to 6 months

Title

Change in Inflammatory Biomarkers Levels (SFTPD) in Plasma Samples as Assessed by ELISA

Description

Time Frame

From baseline up to 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

45 Years

Maximum Age & Unit of Time

79 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically confirmed bronchial dysplasia in ≥ 1 site AND meets one of the following criteria: Current or former smoker with ≥ a 30 pack-year smoking history and no history of lung cancer Stage 0 or I non-small cell lung cancer (NSCLC) curatively treated by surgery (local ablation or resection), adjuvant chemotherapy, or radiotherapy with a ≥ 30 pack-year smoking history At least 6 months since prior surgery, adjuvant chemotherapy, or radiotherapy No current evidence of lung cancer by CT scan No non-calcified lung nodules ≥ 10 mm diameter on spiral CT scan unless cancer is ruled out by PET/CT scan or by biopsy ECOG performance status 0-1 Hemoglobin normal Leukocyte count ≥ 3,000/mm³ Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Total bilirubin ≤ 1.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 1.5 times ULN ALT and AST ≤ 1.5 times ULN BUN ≤ 1.5 times ULN Chloride ≤ 1.5 times ULN Total CO_2 ≤ 1.5 times ULN Sodium ≤ 1.5 times ULN Calcium ≤ 1.5 times ULN Potassium ≤ 1.5 times ULN Phosphorus ≤ 1.5 times ULN Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 30mL/min Fasting blood glucose normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No cancer within the past 3 years except stage 0 or I NSCLC, nonmelanomatous skin cancer, localized prostate cancer, carcinoma in situ of the cervix, or superficial bladder cancer that was treated > 6 months ago No concurrent uncontrolled illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Severe chronic obstructive pulmonary disease requiring supplemental oxygen Uncontrolled hypertension Psychiatric illness or social situation that would limit compliance with study requirements No schizophrenia or bipolar disorder No diabetes No requirement for supplemental oxygen (continuous or intermittent) SaO_2 ≥ 90% on room air No history of allergic reactions attributed to inositol No history of allergies to any ingredient in the study agent or placebo No other concurrent investigational agents At least 7 days since prior anticoagulant use (e.g., coumadin or heparin) More than 6 months since prior participation in another chemoprevention clinical trial No prior pneumonectomy No prior solid organ transplantation No concurrent lithium, carbamazepine, or valproate No concurrent use of other natural health products containing inositol

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Paul Limburg

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Arizona

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85259

Country

United States

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

Albuquerque Veterans Administration Medical Center

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87108-5128

Country

United States

Facility Name

BCCA-Vancouver Cancer Centre

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V5Z 4E6

Country

Canada

12. IPD Sharing Statement

Learn more about this trial

Inositol in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia

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