Phase I Chemoprevention Trial With Green Tea Polyphenon E & Erlotinib in Patients With Premalignant Lesions of the Head & Neck

Inclusion Criteria

- Participants with premalignant lesions (mild dysplasia, moderate dysplasia, severe
dysplasia, or carcinoma in situ) of the head and neck, as confirmed by biopsy within
the 4 months prior to study entry or a treated primary T1N0 or T2N0 squamous cell
carcinoma will be eligible.

- For patients with T1N0 or T2N0 treated squamous cell carcinoma, they must have been
free of disease for a minimum period of 8 weeks, up to a maximum of 3 years following
completion of surgery and/or radiotherapy.

- Eligible tumor and premalignant lesion sites include oral cavity (buccal mucosal,
gingival, floor of mouth, dorsal/ventral tongue, pharyngeal wall), oropharynx, larynx
(glottis, supraglottis, subglottis, epiglottis), hypopharynx paranasal sinus and nasal
cavity.

- Patients with a treated tumor 1-node 0 (T1N0) or tumor 2-node 0 (T2N0) squamous cell
carcinoma may have oral premalignant lesions (i.e., hyperplasia, dysplasia, carcinoma
in situ) at the time of study entry (provided their Stage I or II disease has been
definitively treated).

- Lesion sites include oral cavity (buccal mucosa, gingival, floor of mouth,
dorsal/ventral tongue, pharyngeal wall), oropharynx, hypopharynx,larynx (glottis,
supraglottis, subglottis, epiglottis), nasopharynx and paranasal sinuses.

- Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-1.

- No medical contraindications for flexible laryngoscopy using topical anesthesia, and
in the setting of a contraindication to topical anesthesia, general anesthesia may not
be used as a substitute.

- General anesthesia, if indicated, is acceptable in patients whose lesions would
require general anesthesia for laryngoscopy and biopsy according to routine standard
of care.

- Blood counts: total neutrophil count > 1,500/mm³; platelet count > 100,000/mm³.

- Adequate liver function:

- Total bilirubin level ≤ 1.5 times upper limit normal (ULN)

- Albumin > 2.5 g/dl

- Alkaline phosphatase, aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) ≤ 2.5 times ULN

- Adequate renal function: serum creatinine < 1.5 mg/dl.

- Hemoglobin level ≥ 11gm/dl (age adjusted if appropriate) provided by the reference
laboratory performing the test.

- Patients not taking warfarin must have prothrombin time (PT)/partial thromboplastin
time (PTT) levels ≤ 1.5 times the upper limit of normal provided by the reference
laboratory performing the test.

- Adequate pulmonary function: forced expiratory volume at one second (FEV1) and forced
vital capacity (FVC) at least 60% predicted value by spirometry.

- Signed written informed consent.

- The effects of polyphenon E on the developing human fetus at the recommended dose are
unknown. For this reason and because polyphenon E may be teratogenic, women of
child-bearing potential and men must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for the duration
of study participation. Should a woman become pregnant or suspect she is pregnant
while participating in this study, she should inform her study physician immediately.

- Women of child-bearing potential must also have a negative urine pregnancy test
(β-HCG) within 72 hours of receiving treatment.

- Must be able to swallow the oral doses of erlotinib and PPE.

- Must be willing to abstain from drinking green tea or taking supplements containing
green tea or green tea compounds, for the duration of the investigation and for 30
days prior to study entry.

- Please note that patients with a treated T1N0 or T2N0 squamous carcinoma and who do
not have a pre-malignant measurable lesion at the time of study entry will not be
subjected to a biopsy but will have cytobrush samples taken as specified in the
protocol.

Exclusion Criteria

- Because no dosing or adverse event data are currently available on the use of
Polyphenon E in participants < 18 years of age, children are excluded from this study.

- Participants with hyperplasia, in absence of dysplasia or carcinoma in situ, will be
excluded because there is possibly no benefit.

- Participants with acute intercurrent illness or those who had surgery within the
preceding 4 weeks unless they have fully recovered.

- History of previous malignancies unless the cancer was stage I or II and rendered free
of disease more than 1 year.

- Participants who are pregnant or breast feeding. Pregnant women are excluded from this
study because Polyphenon E is an investigational agent with the potential for
teratogenic or abortifacient effects. Because there is an unknown but potential risk
for adverse events in nursing infants secondary to treatment of the mother with
Polyphenon E, breastfeeding should be discontinued if the mother is treated with
Polyphenon E.

- Not practicing adequate contraception if the participants are of child bearing
potential.

- Uncontrolled intercurrent illness including, but not limited to, severe active
infection, symptomatic congestive heart failure, myocardial infarction within the past
six months, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements are
excluded.

- Documented history of coagulopathy such as hemophilia or Von Willebrand's disease or
inherited thrombophilia.

- Hypertension not adequately controlled by medication (i.e. systolic blood pressure ≥
150 and/or diastolic blood pressure ≥ 90 on at least two separate readings).

- History of congestive heart failure (CHF) greater than New York Heart Association
(NYHA) Grade II.

- Participants who exhibit confusion, disorientation, or have a history of major
psychiatric illness which may impair their understanding of the informed consent.

- Taking epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors within 3
months of study entry.

- Documented history of interstitial lung disease or pulmonary fibrosis.

- Known connective tissue disease.

- Patients who have participated in a clinical trial of an investigational drug within
12 months prior to enrollment.

- History of liver disease or AST and ALT ≥ 2.5 times ULN on screening.

- Consumption of green tea or supplements containing green tea or tea extract within 30
days prior to enrollment.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to polyphenon E, tea, or any of the inactive ingredients present in the
active or placebo drug products, including gelatin capsules.

- Any condition which would make the subject, in the opinion of the investigator,
unsuitable for the study.