Combination Chemotherapy With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck

PRIMARY OBJECTIVES:

I. Assess the efficacy of adding erlotinib hydrochloride (erlotinib) to chemotherapy to
improve progression free survival in patients with metastatic or recurrent squamous cell
carcinoma of the head and neck.

SECONDARY OBJECTIVES:

I. Evaluate overall survival, response rate, disease control rate, and duration of response
by treatment with or without erlotinib.

II. Evaluate quality of life (patient reported outcomes) by treatment with or without
erlotinib.

III. Evaluate the safety profile of erlotinib in combination with chemotherapy. IV. Correlate
the occurrence of erlotinib-induced rash with outcomes. V. To evaluate the steady-state
pharmacokinetics of erlotinib. VI. To explore the prognostic and predictive value of
epidermal growth factor receptor related biomarkers and other biomarkers, including blood and
tissue proteomic and blood and tissue genomic markers, that may be associated with clinical
outcomes.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive docetaxel intravenously (IV) over 1 hour and cisplatin IV over 2
hours or carboplatin IV over 2 hours on day 1, and erlotinib hydrochloride orally (PO) daily
on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease
progression and unacceptable toxicity. Patients achieving complete response, partial
response, or stable disease may continue erlotinib hydrochloride treatment.

ARM B: Patients receive docetaxel and cisplatin or carboplatin as in Arm I and placebo PO
daily on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of
disease progression and unacceptable toxicity. Patients achieving complete response, partial
response, or stable disease may continue placebo treatment.

After completion of study treatment, patients are followed up at 30 days.

Inclusion Criteria:

- Histologically confirmed metastatic or recurrent squamous cell carcinoma of the head
and neck (SCCHN) of the oral cavity, oropharynx, hypopharynx or larynx; metastatic or
recurrent lesions of the nasopharynx and sinus are excluded

- Radiologically 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; measurable lymph nodes are required to be >= 15 mm in size (short axis diameter)

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2

- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

- Platelet count >= 100 x 10^9/L

- Total bilirubin =< upper limit of normal (ULN) (excluding Gilbert's disease)

- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x
ULN

- Alkaline phosphatase =< 2.5 x ULN

- Serum creatinine =< 1.5 x ULN

- Patients with reproductive potential (e.g., females menopausal for less than 1 year
and not surgically sterilized) must practice effective contraceptive measures for the
duration of study drug therapy and for at least 30 days after completion of study drug
therapy; female patients of childbearing potential must provide a negative pregnancy
test (serum or urine) =< 14 days prior to treatment initiation

- Written informed consent to participate in the study according to the investigational
review board (IRB) or independent ethics committee (IEC)

Exclusion Criteria:

- Histology other than squamous cell carcinoma

- Primary sites other than oral cavity, oropharynx, hypopharynx, and larynx

- Prior palliative chemotherapy for metastatic or recurrent disease

- Prior biological therapy for metastatic or recurrent disease within 3 weeks prior to
randomization

- Patients with known, untreated brain metastases; patients with treated (irradiated or
resected) brain metastases are eligible if treatment was completed more than 28 days
prior to study entry and if clinical neurologic function is stable

- Pre-existing peripheral neuropathy >= grade 2

- History of poorly controlled gastrointestinal disorders that could affect the
absorption of the study drug (e.g., Crohn's disease, ulcerative colitis); patients
requiring feeding tubes are permitted

- Other active malignancies requiring chemotherapy treatment within 2 years prior to
randomization, except for adequately treated basal cell or squamous cell skin cancer
or in situ cervical or breast cancer or superficial, resected melanoma

- Serious underlying medical condition which would impair the ability of the patient to
receive protocol treatment, in the opinion of the treating physician

- History of allergic reactions to compounds of similar chemical composition to the
study drugs (docetaxel, cisplatin, carboplatin, erlotinib or their excipients), or
other drugs formulated with polysorbate 80

- Any concurrent anti-cancer therapy, excluding hormonal therapy for prostate or breast
cancer

- Dementia or significantly altered mental status that would prohibit the understanding
and giving of informed consent

- Women who are pregnant or breast-feeding and women or men not practicing effective
birth control