Exploring the Impact of Two-week Kava on the Metabolism of Nicotine and NNK

Tobacco smoking is the leading cause of head and neck cancer in the United States and a
significant portion of head/neck cancer survivors continue to smoke even though smoking
negatively impacts their clinical outcomes and increases chance of recurrence. Two tobacco
chemicals, NNK and nicotine, are respectively responsible for the increased recurrence risk
and tobacco addiction. Kava s properties as a proven anxiolytic and a potential carcinogen
detoxifier warrant an investigation of its effects on the metabolism of these two tobacco
chemicals among head/neck cancer survivors who continue to smoke. The results will
identifying surrogate biomarkers and provide information regarding kava s potential as a
future intervention to both promote smoking cessation and reduce carcinogenesis risk.

Primary Objective:

To explore the feasibility of recruitment of participants, adherence rate, acceptability of
treatment and completion rate with 14 day dietary supplement kava treatment in head and neck
cancer patients who continue to smoke.

To evaluate distribution of change in nicotine and NNK metabolism after 14 day kava
treatment.

Exploratory Objective:

To evaluate distribution of change in mood after 14 day kava treatment. To evaluate
prevalence of pain and pain medication use and distribution of change in pain and pain
medication consumption after 14 day kava treatment.

Inclusion Criteria:

Individuals eligible for study participation must meet the following criteria:

- Must be a current smoker with history of head and neck cancer.

- Must be at least 3 months out from completing definitive cancer treatment.

- Must not be undergoing active treatment for cancer or have known recurrence.

- Subjects must have adequate organ function, as defined by: the clinical chemistry
analysis of ALT, ALP, AST and total bilirubin within the normal range.

- Subjects must have access to a functional telephone.

- Written informed consent obtained from the subject or the subject's legal
representative and the ability for the subject to comply with all the study-related
procedures.

- Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study. Prior to study enrollment,
women of childbearing potential must be advised of the importance of avoiding
pregnancy during trial participation and the potential risk factors for an
unintentional pregnancy.

WOCBP include any woman who has experienced menarche and who has not undergone successful
surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy)
or who is not post-menopausal. Post-menopause is defined as:

- Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or

- For women with irregular menstrual periods who are taking hormone replacement therapy
(HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35
mIU/mL.

- Males with female partners of child-bearing potential must agree to use
physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy)
throughout the study.

Exclusion Criteria:

Subjects with any of the following will not be eligible for study participation:

- Known liver disease as defined by the following elevated serum levels of AST, ALK
Phos, ALT or total bilirubin:

- Consumption of more than three alcoholic drinks per day

- D. Subjects must not have been diagnosed with any liver dysfunction

- Subjects who regularly take more than the recommended dose of acetaminophen for pain
management.

- Females or males of childbearing potential who are unwilling or unable to use an
acceptable method to avoid pregnancy for the entire study period.

- Females who are pregnant or breastfeeding.

- History of any other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of protocol therapy or that might affect the interpretation of
the results of the study or that puts the subject at high risk for treatment
complications, in the opinion of the treating physician.

- Prisoners or subjects who are involuntarily incarcerated.

- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical illness.

- Subjects demonstrating an inability to comply with the study and/or follow-up
procedures.