Carboplatin, Paclitaxel, Cetuximab, and Erlotinib Hydrochloride in Treating Patients With Metastatic or Recurrent Head and Neck Squamous Cell Cancer

PRIMARY OBJECTIVES:

I. To determine the objective response rate when erlotinib is added to combination
carboplatin/paclitaxel/cetuximab systemic therapy in metastatic/recurrent head and neck
cancer.

SECONDARY OBJECTIVES:

I. Secondary endpoints will be toxicity, overall survival, and laboratory correlates to
determine if epidermal growth factor receptor (EGFR) signaling is more effectively inhibited
after the addition of erlotinib than it is after chemotherapy/cetuximab without erlotinib.

OUTLINE:

Patients receive cetuximab intravenously (IV) over 60 minutes, paclitaxel IV over 1 hour,
and carboplatin IV over 30 minutes on day 1. Beginning in course 2, patients also receive
erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Courses repeat every 21
days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Criteria:

- Histologically confirmed squamous cell carcinoma of the head and neck that is
metastatic or recurrent

- No prior systemic therapy for metastatic/recurrent disease

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Prior chemotherapy in the induction, organ preservation or adjuvant setting is
permitted if it was completed more than 4 months prior to enrollment on the current
study

- Prior cetuximab is permitted if it was given for no more than 9 doses in combination
with radiation therapy or chemoradiation therapy for initial treatment of locally
advanced disease

- No prior erlotinib, gefitinib or lapatinib therapy is permitted; nor is prior
exposure to any investigational EGFR or panErbB reversible or irreversible inhibitor
or any prior panitumumab or investigational EGFR-directed monoclonal antibody
permitted

- Hemoglobin > 9.0 G/dl

- Absolute neutrophil count (ANC) > 1500 cells/mcl

- Creatinine (Cr) < 1.8

- Total bilirubin =< the institution's upper limit of normal (ULN), aspartate
aminotransferase (AST) and alanine transaminase (ALT) < 2 X ULN

- No chronic active viral infection

- No other malignancy within 3 years

- No chronic diarrheal condition

- Females should not be pregnant or breast feeding because chemotherapy may be harmful
to the fetus or the nursing infant; also, the effects of erlotinib and cetuximab on
the developing human fetus are unknown

- All females of childbearing potential must have a blood test or urine study within 2
weeks prior to randomization to rule out pregnancy

- Women of childbearing potential and sexually active males must use an accepted and
effective method of contraception while on treatment and for three months after the
completion of treatment

- Patients must have measurable disease based on Response Evaluation Criteria In Solid
Tumors (RECIST); baseline measurements and evaluations must be obtained within < 4
weeks of randomization; all areas of disease should be recorded and mapped out in
order to assess response and uniformity of response to therapy; disease in previously
irradiated sites is considered measurable if there has been unequivocal disease
progression or biopsy-proven residual carcinoma following radiation therapy;
persistent disease without clear-cut progression after radiotherapy can be considered
measurable if biopsy-proven at least 8 weeks after completion of radiation therapy

- Patients with a prior history of squamous cell or basal carcinoma of the skin or in
situ cervical cancer must have been curatively treated; patients with a history of
other prior malignancy must have been treated with curative intent and must have
remained disease-free for 3 years post diagnosis

- No current peripheral neuropathy > grade 2 at time of randomization

- Patients must not have any co-existing condition that would preclude full compliance
with the study

- Human immunodeficiency virus (HIV) positive patients receiving combination
anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with erlotinib

- Patients must have no history of allergic reaction to murine proteins

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

- Patients must not be receiving other investigational anti-cancer therapy

- Patients with brain metastases are not eligible

- Both men and women and members of all races and ethnic groups are eligible for this
trial