Clinical trial NCT00691132
Conditions: Lung Cancer Tobacco Use Disorder
Keywords: non-small cell lung cancer small cell lung cancer tobacco use disorder
Sponsor: University of Minnesota
Start date: 2009-02-01; Completion date: 2013-01-01
Enrollment: 107 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of phenethyl isothiocyanate may prevent lung cancer in people who smoke cigarettes.

PURPOSE: This randomized clinical trial is studying phenethyl isothiocyanate to see how well it works in preventing lung cancer in smokers.

Detailed description:
OBJECTIVES:

Primary

* To determine whether oral phenethyl isothiocyanate (PEITC) affects urinary levels of biomarkers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism in current smokers.

Secondary

* To determine the effect of GSTM1 genotype on PEITC's impact on urinary biomarkers of NNK metabolism.
* To determine the effect of GSTM1 genotype on the metabolism and excretion of PEITC as measured by urinary levels of its major metabolite.
* To determine whether oral PEITC affects molecular markers of cell proliferation (Ki-67) and apoptosis (caspase-3 and TUNEL) in bronchial tissue.

OUTLINE: Patients are stratified according to GST genotypes (GSTM1 null-null genotype vs GSTM1-positive genotype). All participants are initially enrolled in the short-term trial. After the completion of the short-term trial, only those participants meeting certain criteria may proceed to the long-term trial.

* Short-term trial: Participants are randomized to 1 of 2 treatment arms.

  * Arm I: Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month. Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in week 2 and oral placebo four times daily for 5 days in week 4. Participants keep a diary of all food and beverages consumed on the days that PEITC or placebo are taken.
  * Arm II: Participants receive oral placebo four times daily for 5 days in week 2 and oral PEITC four times daily for 5 days in week 4. Participants are also asked to smoke only deuterated NNK cigarettes, record the number of cigarettes smoked and alcoholic drinks consumed each day, and keep a food and beverage diary as in arm I.

After completion of the short-term trial, participants undergo a wash-out period for 1 month in which they are asked to resume smoking regular cigarettes. Participants are offered smoking cessation assistance, if desired. Only those participants meeting certain criteria may proceed to the long-term trial after the 1-month wash-out period.

* Long-term trial: Participants are randomized to 1 of 2 treatment arms.

  * Arm I: Participants receive oral PEITC twice daily for 12 months.
  * Arm II: Participants receive oral placebo twice daily for 12 months. Participants in both arms complete a 3-day food diary monthly for 12 months and a food-frequency questionnaire at baseline and at the completion of study treatment.

All participants undergo blood and urine sample collection periodically for laboratory studies. Participants enrolled in the long-term trial also undergo bronchoscopy and tissue biopsy at baseline and at the completion study treatment. Urine samples are examined by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) for various biomarkers. Tissue samples are examined by IHC for Ki-67, TUNEL, and caspase-3 expression.

Arms: arm 1: Participants are asked to smoke only deuterated NNK cigarettes (provided by the study) and record the exact number of cigarettes smoked and alcoholic drinks consumed each day for 1 month. Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in week 2 and oral placebo four times daily for 5 days in week 4. Participants keep a diary of all food and beverages consumed on the days that PEITC or placebo are taken. arm 2: Participants receive oral placebo four times daily for 5 days in week 2 and oral PEITC four times daily for 5 days in week 4. Participants are also asked to smoke only deuterated NNK cigarettes, record the number of cigarettes smoked and alcoholic drinks consumed each day, and keep a food and beverage diary as in arm I.
Interventions: intervention 1: phenethyl isothiocyanate intervention 2: placebo
Intervention descriptions: intervention 1: Given orally intervention 2: Given orally

Protocol documents: