Phenethyl Isothiocyanate in Preventing Lung Cancer in Smokers

NCT00691132 | Completed Phase 2 Results DMC

• 3 other identifiers: 2007NT127R01CA1222440712M22651
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer; Tobacco Use Disorder

Keywords

non-small cell lung cancer; small cell lung cancer; tobacco use disorder

Outcome Measures

Primary Outcomes (2)

• Urinary Levels of Biomarkers of NNK Metabolism

  Urinary levels of Total ITC and PEITC-NAC by treatment sequence groups and treatment period.

  2 periods, 5 days each on PEITC or Placebo, with washout week between

• Urinary Levels of Biomarkers of NNK Metabolism

  The ratio of urinary \[pyridine-D4\]hydroxy acid : total \[pyridine-D4\]NNAL will be measured. This ratio is not expected to be influenced by the number of cigarettes smoked per day, or smoking topography.

  After 5 days of treatment

Secondary Outcomes (4)

• Effects of GSTM1 Genotype on Phenethyl Isothiocyanate (PEITC)-NNK Association and on the Metabolism and Excretion of PEITC

  After 5 days of PEITC treatment

• Effects of GSTT1 Genotype on Phenethyl Isothiocyanate (PEITC)-NNK Association and on the Metabolism and Excretion of PEITC

  After 5 days of treatment

• Combined Effects of GSTM1 and GSTT1 Genotype on Phenethyl Isothiocyanate (PEITC)-NNK Association and on the Metabolism and Excretion of PEITC

  After 5 days of treatment

• Urinary Levels of [Pyridine-D4]Hydroxy Acid:Total [Pyridine-D4]NNAL Ratio by GSTM1 and GSTT1 Genotype.

  After 5 days of treatment

Study Arms (2)

PEITC - Placebo (short-term trial)

EXPERIMENTAL

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.

Drug: phenethyl isothiocyanate; Other: placebo

Placebo - PEITC (short-term trial)

EXPERIMENTAL

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.

Drug: phenethyl isothiocyanate; Other: placebo

Interventions

phenethyl isothiocyanate DRUG

Given orally

Also known as: PEITC

PEITC - Placebo (short-term trial); Placebo - PEITC (short-term trial)

placebo OTHER

Given orally

PEITC - Placebo (short-term trial); Placebo - PEITC (short-term trial)

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Initial from phone interview:
• Currently smoking 10-45 cigarettes per day for the past year;
• Between the ages of 21 and 70 years;
• In apparently good physical health with no unstable medical conditions including seizures or cancer;
• In stable and good mental health, i.e., currently do not experience unstable or untreated psychiatric diagnosis, including substance abuse, as determined by the DSM-IV criteria, during the past six months;
• Not using any other tobacco or nicotine-containing products;
• Not on methadone maintenance or stimulants such as ephedra; not a regular user of street drugs and if uses occasionally, willing to abstain during the study; not taking any drugs known to be P4501A6 substrates such as phenobarbital, rifampicin, dexamethasone, ketoconazole, methoxsalen, pilocarpine, or tranylcypromine due to their role in NNK metabolism;
• Does not average more than 21 alcoholic drinks per week;
• Willing to perform study activities such as having blood sample drawn, urine collection, multiple clinic visits;
• For female subjects of child bearing potential, not known to be pregnant or nursing, or planning to become pregnant within next 12 months.
• For enrollment in the Short-Term Trial:
• Subjects who are generally healthy with liver enzyme and blood count values within the ranges shown below based on blood samples drawn at the second screening visit. Specifically:
• White blood cells ≥ 3,000/mL
• Total bilirubin ≤ 1.5 x upper limits of normal (ULN)
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN

You may not qualify if:

• Subjects with uncontrolled hypertension, uncontrolled diabetes mellitus, unstable coronary artery disease, history of cancer other than non-melanoma skin cancer, and pregnant or lactating women will not be eligible.

Sponsors & Collaborators

• University of Minnesota: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (2)

• Yuan JM, Stepanov I, Murphy SE, Wang R, Allen S, Jensen J, Strayer L, Adams-Haduch J, Upadhyaya P, Le C, Kurzer MS, Nelson HH, Yu MC, Hatsukami D, Hecht SS. Clinical Trial of 2-Phenethyl Isothiocyanate as an Inhibitor of Metabolic Activation of a Tobacco-Specific Lung Carcinogen in Cigarette Smokers. Cancer Prev Res (Phila). 2016 May;9(5):396-405. doi: 10.1158/1940-6207.CAPR-15-0380. Epub 2016 Mar 7.

  PMID: 26951845 RESULT

• Dinh TN, Parat MO, Ong YS, Khaw KY. Anticancer activities of dietary benzyl isothiocyanate: A comprehensive review. Pharmacol Res. 2021 Jul;169:105666. doi: 10.1016/j.phrs.2021.105666. Epub 2021 May 12.

  PMID: 33989764 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Tobacco Use Disorder; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma

Interventions

phenethyl isothiocyanate

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms

Results Point of Contact

• Title: Dr. Dorothy Hatsukami
• Organization: University of Minnesota

hatsu001@umn.edu

612-626-2121

Study Officials

• Dorothy K. Hatsukami, PhD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2008
• First Posted: June 5, 2008
• Study Start: February 1, 2009
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: May 12, 2017
• Results First Posted: April 4, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)