Phase I Chemoprevention Trial With Green Tea Polyphenon E & Erlotinib in Patients With Premalignant Lesions of the Head & Neck
Phase I Chemoprevention Trial With Green Tea Polyphenon E & Erlotinib in Patients With Premalignant Lesions of the Head & Neck
The purpose of this study is to test the preventive effects of a combination of drugs:
 polyphenon E (PPE) derived from green tea extracts, and erlotinib. Because this combination
 of drugs has not been tested in humans before for the prevention of cancer, it is not clear
 which dose of each agent will be optimal in combination.

 We will test the safety of the combination of PPE and erlotinib and see what effects (good
 and/or bad) it has on the patient's premalignant lesion, and find the highest dose of each
 agent that can be given in combination without causing severe side effects.
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.