Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Phenethyl Isothiocyanate in Preventing Lung Cancer in Smokers

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs No phase specified Biomarker/Laboratory analysis, Prevention Approved-not yet active 21 to 70 NCI UMN-2007NT127 PEITC, NCT00691132

Objectives

Primary

1. To determine whether oral phenethyl isothiocyanate (PEITC) affects urinary levels of biomarkers of NNK metabolism in current smokers.

Secondary

1. To determine the effect of GSTM1 and GSTT1 genotypes on PEITC’s impact on urinary biomarkers of NNK metabolism.
2. To determine the effect of GSTM1 and GSTT1 genotypes on the metabolism and excretion of PEITC as measured by urinary levels of its major metabolite.
3. To determine whether oral PEITC affects molecular markers of cell proliferation (Ki-67) and apoptosis (caspase-3 and TUNEL) in bronchial tissue.

Entry Criteria

Disease Characteristics:

• Currently smokes 10-45 “light or ultralight” cigarettes (with nicotine content ≤ 0.8 mg per cigarette) per day for the past year*
  • Not currently using any other tobacco or nicotine-containing products

   [Note: *Participants enrolled in the long-term trial must currently smoke ≥ 20 cigarettes/day AND have a cumulative smoking history of ≥ 20 pack years]




• In apparently good physical health



• Meets 1 of the following criteria:
  • GSTM1 null-null and GSTT1 null-null genotypes*
  • GSTM1-positive and GSTT1-positive genotypes

   [Note: *Participants enrolled in the long-term trial must possess both the GSTM1 null-null and the GSTT1 null-null genotypes]

Prior/Concurrent Therapy:

• No concurrent drugs known to be P4501A2 substrates, including any of the following:
  • Acetaminophen
  • Phenacetin
  • Tamoxifen
  • Bupropion
  • Theophylline

Patient Characteristics:

• Liver enzymes normal
• No unstable medical conditions
• No concurrent seizures
• No concurrent cancer
• In stable and good mental health (i.e., no unstable or untreated psychiatric diagnosis, including substance abuse, within the past 6 months)
• Not pregnant or nursing
• Good candidate for bronchoscopy, as determined by a primary care physician*
• No uncontrolled hypertension*
• No uncontrolled diabetes mellitus*
• No unstable coronary artery disease*
• No history of cancer other than nonmelanoma skin cancer*
• No consumption of cruciferous vegetables during the short-term trial

 [Note: *For participants enrolled in the long-term trial]

Expected Enrollment

Outcomes

Urinary levels of biomarkers of NNK metabolism as measured by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS)

Effects of GSTM1 and GSTT1 genotypes on phenethyl isothiocyanate (PEITC)-NNK association and on the metabolism and excretion of PEITC as measured by high-performance liquid chromatography (HPLC)
Histopathological evaluation of lung lesions
Molecular markers of cell proliferation (Ki-67) and apoptosis (caspase-3 and TUNEL) in bronchial tissue as measured by immunohistochemistry

Outline

Patients are stratified according to GST genotypes (GSTM1 null-null and GSTT1 null-null genotypes vs GSTM1-positive and GSTT1-positive genotypes). 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 each day in weeks 0-3. Participants receive oral phenethyl isothiocyanate (PEITC) four times daily for 5 days in week 1 and oral placebo four times daily for 5 days in week 3. 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 1 and oral PEITC four times daily for 5 days in week 3. Participants are also asked to smoke only deuterated NNK cigarettes, record the number of cigarettes smoked 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.

Trial Contact Information

Trial Lead Organizations

Masonic Cancer Center at University of Minnesota

Jian-Min Yuan, PhD, Principal investigator		Ph: 612-625-8056; 888-226-2376

Registry Information
Official Title		Randomized Trial of PEITC as a Modifier of NNK Metabolism in Smokers
Trial Start Date		2008-06-01 (estimated)
Trial Completion Date		2013-06-01 (estimated)
Registered in ClinicalTrials.gov		NCT00691132
Date Submitted to PDQ		2008-05-16
Information Last Verified		2008-12-28
NCI Grant/Contract Number		CA122244, CA77598