Randomized Trial of Fluticasone in Bronchial Premalignancy

Condition(s) targeted: Bronchogenic Carcinoma

Intervention: Fluticasone propionate (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: VU University Medical Center

Official(s) and/or principal investigator(s):
Egbert F Smit, MD PHD, Principal Investigator, Affiliation: VU University Medical Center

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

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 design: Prevention, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study

Primary outcome: Reversal of histological abnormality bronchial biopsies at 6 months

Secondary outcome:

Reversal of suprabasal p53 staining at 6 months

Reversal of elevated hTERT mRNA levels at 6 months

Reversal of increased KI-67 at 6 months

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

VU medical center, Amsterdam 1081HV, Netherlands

the Netherlands Cancer Institute / Antoni van Leeuwenhoek Hospital, Amsterdam 1066CX, Netherlands

Related publications:

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.

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.

Starting date: February 2002
Ending date: December 2005
Last updated: November 29, 2006