Phase I Chemoprevention Study With Green Tea and Erlotinib in Patients With Premalignant Lesions of the Head and Neck

Inclusion Criteria

Inclusion Criteria

1. Have premalignant lesions (mild dysplasia, moderate dysplasia, severe dysplasia, or
carcinoma in situ) of the head and neck, confirmed by biopsy within the 3 months
prior to study entry

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

3. ECOG/Zubrod performance status of 0-1

4. Age ≥ 18 years old

5. 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.

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

7. Total neutrophil count >1,500/mm3; platelet count >100,000/mm3

8. Adequate liver function: total bilirubin level <2.0 mg/dl; albumin >2.5 g/dl;
transaminase (AST and ALT) ≤ upper normal limit (ULN)

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

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

11. Patients not taking warfarin must have PT/PTT levels ≤ 1.5 times the ULN provided by
RL performing test

12. Adequate pulmonary function: FEV1 and FVC at least 60% predicted value by spirometry

13. Participants must have a signed written informed consent

14. Polyphenon E may be teratogenic, so 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.

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

16. Ability to swallow oral doses of erlotinib and PPE

17. 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

Exclusion Criteria

1. Participants <18 years of age children are excluded

2. Participants with hyperplasia will be excluded because there is possibly no benefit.

3. Acute intercurrent illness or those who had surgery within the preceding 4 weeks
unless fully recovered

4. Previous malignancies unless the cancer was stage I or II and rendered free of
disease more than 1 year

5. Participants who are pregnant or breast feeding. Polyphenon E is an Investigational
agent with teratogenic or abortifacient potential. There is an unknown but potential
risk for adverse events in nursing infants secondary to treatment of the mother with
Polyphenon E, so breastfeeding should be discontinued if the mother is treated with
Polyphenon E

6. Patients who are not practicing adequate contraception if the participants are of
child bearing potential

7. History of cardiovascular events including angina, unstable angina, arrhythmia, in
addition to recent myocardial infarction (<6 months), or history of cerebrovascular
disease

8. Uncontrolled intercurrent illness not limited to ongoing or active infection,
symptomatic congestive heart failure, unstable angina pectoris, serious cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

9. Documented history of coagulopathy and/or those taking warfarin or
warfarin-derivative anticoagulants

10. Hypertension not adequately controlled by medication

11. Documented history of congestive heart failure (CHF) greater than New York Heart
Association (NYHA) Grade II

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

13. Use of EGFR tyrosine kinase inhibitors within 3 months of study entry

14. Documented history of interstitial lung disease

15. Known connective tissue disease

16. Participation in clinical trial of an investigational drug within 12 months prior to
enrollment

17. History of liver disease or elevated AST/ALT on screening

18. Consumption of green tea/supplements containing green tea/tea extract within 30 days
prior to enrollment

19. Allergy to compounds of similar chemical or biologic composition to polyphenon E,
tea, or any of the inactive ingredients present in the drug products including
gelatin capsules

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