Phenethyl Isothiocyanate in Preventing Lung Cancer in Smokers
Condition: Lung Cancer; Tobacco Use Disorder
MeSH terms: Lung Neoplasms; Tobacco Use Disorder
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): phenethyl isothiocyanate; placebo
Intervention type(s): Drug; Other
Intervention description(s): Given orally; Given orally
Other intervention name(s): PEITC
Intervention MeSH terms: Phenethyl isothiocyanate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: non-small cell lung cancer; small cell lung cancer; tobacco use disorder