A Phase 2 Trial of GW572016 in Patients With Metastatic and Recurrent Squamous Cell Carcinomas of the Head and Neck

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed metastatic or recurrent
squamous cell carcinoma of the head/neck; these include tumors arising in the oral
cavity, oropharynx, nasopharynx, hypopharynx, glottis, or ethmoid/maxillary sinus;
patients with localized disease must have failed primary therapy radiotherapy,
surgery, and/or chemotherapy); patients with single site or regional recurrence that,
in view of the Principal Investigator (PI) or treating physician is potentially
curable by resection or by re-irradiation program, must have declined such therapies

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
20 mm with conventional techniques or as >= 10 mm with spiral computed tomography
(CT) scan; one or more sites of metastatic or recurrent disease must be accessible
for needle biopsy

- No more than 2 prior chemotherapy regimens; no prior treatment with tyrosine kinase
inhibitors or antibodies to the epidermal growth factor receptor (EGOR) or human
epidermal growth factor receptor 2 (HER2)/neu; prior chemotherapy or radiation
therapy completed at least 4 weeks prior to treatment with GW572016

- Life expectancy of greater than three months

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

- Leukocytes > 3,000/uL

- Absolute neutrophil count > 1,500/uL

- Platelets > 100,000/uL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2.5 X institutional upper limit of normal

- Creatinine within normal institutional limits OR creatinine clearance > 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

- Cardiac ejection fraction within the institutional range of normal as measured by
echocardiogram or multigated acquisition (MUGA) scan; note that baseline and on
treatment scans should be performed using the same modality and preferably at the
same institution

- Eligibility of patients receiving medications or substances known to affect, or with
the potential to affect the activity or pharmacokinetics of GW572016 will be
determined following review of their use by the Principal Investigator; patients
requiring oral anticoagulants (coumadin, warfarin) are eligible provided there is
increased vigilance with respect to monitoring international normalized ratio (INR);
if medically appropriate and treatment available, the investigator may also consider
switching these patients to low molecular weight (LMW) heparin, where an interaction
with GW572016 is not expected

- The effects of GW572016 on the developing human fetus at the recommended therapeutic
dose are unknown; for this reason, women of child-bearing potential and men must
agree to use adequate contraception (hormonal or barrier method of birth control or
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 treating physician immediately

- Ability to understand and the willingness to sign a written informed consent document

- Able to retain and absorb medication given by mouth or feeding tube

Exclusion Criteria:

- Prior treatment:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or

- Patients who have not recovered from adverse events due to agents administered
more than 4 weeks earlier

- Patients who have had prior treatment with EGFR targeting therapies

- Patients may not be receiving any other investigational agents or receiving
concurrent anticancer therapy

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to GW572016

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

- Pregnant women are excluded from this study because GW572016 is member of the
4-anilinoquinazoline class of kinase inhibitors 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 GW572016,
breastfeeding should be discontinued if the mother is treated with GW572016; human
immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral
therapy are excluded from the study because of possible pharmacokinetic interactions
with GW572016; appropriate studies will be undertaken in patients receiving
combination anti-retroviral therapy when indicated

- Patients with gastrointestinal (GI) tract disease resulting in an inability to take
oral medication, malabsorption syndrome, a requirement for intravenous (IV)
alimentation, prior surgical procedures affecting absorption, uncontrolled
inflammatory GI disease (e.g., Crohn's, ulcerative colitis)

- Concomitant requirement for medication classified as cytochrome P450 3A4 (CYP3A4)
inducer or inhibitor