Clinical trial NCT00407264: Randomized Trial of Fluticasone in Bronchial Premalignancy
Official title: The Influence of Fluticasone Inhalation on Intermediate Markers of Carcinogenesis in the Bronchial Epithelium of a High Risk Population : A Double Blind Placebo-Controlled Randomised Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bronchogenic Carcinoma
Keywords: bronchial squamous metaplasia
bronchial squamous dysplasia
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
name: The Netherlands Cancer Institute
First posted: 2006-12-04
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the efficacy of fluticasone on the development of lung cancer in smokers

Detailed description: Bronchial epithelium exposed to cigarette smoke undergoes a series of histological changes that may ultimately lead to invasive cancer. In rats exposed to cigarette smoke inhaled corticosteroids reduce the number of lung tumors. The purpose of this study is to assess the efficacy of fluticasone on premalignant lesions in volunteers with a smoking history of \>10 pack-years and patients cured of head and neck cancer or lung cancer. Participants are screened for premalignant lesions by bronchoscopy and if these are present randomised to receive a powder inhalation device containing either fluticasone 500 μg or a placebo. After 6 months, biopsies are taken from the same locations. Efficacy of treatment is assessed by reversal of metaplasia/dysplasia; secondary end-points are reversal of increased p53 immunoreactivity and hTERT expression.

Eligibility criteria: Inclusion Criteria:

* signed informed consent
* age over 18
* metaplasia index \> 15%
* over 25 pack years smoking history or history of lung- or head\&neck cancer
* male/female of non-childbearing potential or using approved contraception

Exclusion Criteria:

* use of inhaled/systemic corticosteroid drugs in the preceding 12 months
* contraindications for bronchoscopy/use of fluticasone
* major illness
* Baseline FEV1\<1000ml
* Previous participation in clinical study
* nodules \> 1cm on CT

Primary outcomes:
measure: Reversal of histological abnormality bronchial biopsies at 6 months
Secondary outcomes:
measure: Reversal of suprabasal p53 staining at 6 months
measure: Reversal of elevated hTERT mRNA levels at 6 months
measure: Reversal of increased KI-67 at 6 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: the Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital
city: Amsterdam
country: Netherlands
facility: VU medical center
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: Egbert F Smit, MD PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wattenberg LW, Wiedmann TS, Estensen RD, Zimmerman CL, Galbraith AR, Steele VE, Kelloff GJ. Chemoprevention of pulmonary carcinogenesis by brief exposures to aerosolized budesonide or beclomethasone dipropionate and by the combination of aerosolized budesonide and dietary myo-inositol. Carcinogenesis. 2000 Feb;21(2):179-82. doi: 10.1093/carcin/21.2.179.
citation: Breuer RH, Snijders PJ, Sutedja TG, v d Linden H, Risse EK, Meijer CJ, Postmus PE, Smit EF. Suprabasal p53 immunostaining in premalignant endobronchial lesions in combination with histology is associated with bronchial cancer. Lung Cancer. 2003 May;40(2):165-72. doi: 10.1016/s0169-5002(03)00029-1.