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

NCT00321893 | Completed Phase 2 Results DMC

• 7 other identifiers: NCI-2014-02166MDA-05-5-01MDA-S262/505MDA-2005-0953EUDRACT-2005-004614-32CDR0000470861NCI-2012-02113
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lung Cancer

Keywords

Small cell lung cancer; Non-small cell lung cancer; Budesonide; Entocort EC; Pulmicort Respules; Rhinocort aqua; Aerosol budesonide treatment; Smoking

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (2)

Arm I: Budesonide

EXPERIMENTAL

Inhaled Budesonide 800 ug twice daily for 1 year

Drug: Budesonide

Arm II: Placebo

PLACEBO COMPARATOR

Inhaled placebo twice daily for 1 year

Other: Placebo

Interventions

Budesonide DRUG

Inhaled Budesonide 800 micrograms (ug) twice daily for one year.

Also known as: Entocort EC, Pulmincort Respules, Rhinocort aqua

Arm I: Budesonide

Placebo OTHER

Inhaled placebo twice daily for one year.

Arm II: Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

European Institute of Oncology

Milan, 20141, Italy

Location

Related Publications (3)

• Fumagalli C, Bianchi F, Raviele PR, Vacirca D, Bertalot G, Rampinelli C, Lazzeroni M, Bonanni B, Veronesi G, Fusco N, Barberis M, Guerini-Rocco E. Circulating and tissue biomarkers in early-stage non-small cell lung cancer. Ecancermedicalscience. 2017 Jan 31;11:717. doi: 10.3332/ecancer.2017.717. eCollection 2017.

  PMID: 28194229 DERIVED

• Veronesi G, Szabo E, Decensi A, Guerrieri-Gonzaga A, Bellomi M, Radice D, Ferretti S, Pelosi G, Lazzeroni M, Serrano D, Lippman SM, Spaggiari L, Nardi-Pantoli A, Harari S, Varricchio C, Bonanni B. Randomized phase II trial of inhaled budesonide versus placebo in high-risk individuals with CT screen-detected lung nodules. Cancer Prev Res (Phila). 2011 Jan;4(1):34-42. doi: 10.1158/1940-6207.CAPR-10-0182. Epub 2010 Dec 16.

  PMID: 21163939 DERIVED

• Lazzeroni M, Guerrieri-Gonzaga A, Serrano D, Varricchio MC, Veronesi G, Radice D, Feroce I, Nardi-Pantoli A, Lippman SM, Szabo E, Bonanni B. Budesonide versus placebo in high-risk population with screen-detected lung nodules: rationale, design and methodology. Contemp Clin Trials. 2010 Nov;31(6):612-9. doi: 10.1016/j.cct.2010.08.006. Epub 2010 Aug 16.

  PMID: 20719253 DERIVED

Related Links

• University of Texas (UT) MD Anderson Cancer Center Official Website

MeSH Terms

Conditions

Lung Neoplasms; Small Cell Lung Carcinoma; Carcinoma, Non-Small-Cell Lung; Smoking

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Behavior

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Powel H. Brown, MD, PhD/Professor of Medicine and Cancer Prevention
• Organization: University of Texas MD Anderson

CR_Study_Registration@mdanderson.org

Study Officials

• Giulia Veronesi, MD

  European Institute of Oncology

  STUDY CHAIR

• Scott M. Lippman, MD, FACP

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2006
• First Posted: May 4, 2006
• Study Start: January 1, 2006
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: January 25, 2016
• Results First Posted: April 27, 2015

Record last verified: 2014-10

Locations

IT (1)