Phase II Study of Single-Agent Cetuximab for Treatment of High-Risk Pre-malignant Upper Aerodigestive Lesions

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed high-risk, premalignant lesions of the upper aerodigestive
tract, meeting one of the following criteria:

- Unresectable, diffuse high-grade dysplasia, defined as moderate or severe
dysplasia that is not assessable by physical examination and/or that cannot be
excised by standard surgical techniques

- previously treated HNSCC with persistent or recurrent high grade dysplasia with
no evidence of head and neck malignancy for three months prior to enrollment or
who have successfully completed therapy for head and neck malignancy more than 3
months prior to enrollment.

- Dysplastic lesions with 3p or 9p loss of heterozygosity

- Disease location amenable to endoscopic biopsy in an outpatient clinical setting or
operative biopsy within the routine scheduling and practice of clinical care

- No medical contraindication to biopsy of the target lesion

- Pathology must be reviewed by the Johns Hopkins Hospital Department of Pathology

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- ANC > 1,000/mm³

- Platelet count > 75,000/mm³

- Creatinine clearance > 60 mL/min

- Total serum bilirubin < 1.5 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study therapy

- No concurrent illness likely to preclude study therapy or surgical resection

- Patients with a history of a curatively treated malignancy are eligible provided they
are disease-free and have a survival prognosis that exceeds 5 years

- No evidence of clinically active interstitial lung disease

- Patients with chronic, stable radiographic changes who are asymptomatic are
eligible

- No history or radiological evidence of pulmonary fibrosis

- No acute myocardial infarction within the past 3 months

- No uncontrolled angina, arrhythmia, or congestive heart failure

- No evidence of other severe or uncontrolled systemic disease (e.g., unstable or
uncompensated respiratory, cardiac, hepatic, or renal disease)

- No evidence of any other significant clinical disorder or laboratory finding that
would preclude study participation

- No known severe hypersensitivity to cetuximab or any of its excipients

- No prior hypersensitivity reaction to chimerized or murine monoclonal antibody
therapy

- No severe abnormality of the cornea

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from prior oncologic or other major surgery or biopsy

- More than 30 days since prior non-approved or investigational drugs

- No prior chemotherapy, radiotherapy, or surgery for the premalignant lesions

- No prior EGFR-targeted agents (e.g., cetuximab, gefitinib, or erlotinib)