Sorafenib and Cetuximab in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN):a Phase IB/II Trial

Inclusion Criteria:

- Histologically confirmed squamous cell carcinoma of the head and neck

- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
criteria

- Age > 18 years old

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

- Adequate bone marrow, liver and renal function as assessed by the following:

- Hemoglobin > 9.0 g/dl

- Absolute neutrophil count (ANC) > 1,500/mm3

- Platelet count > 100,000/mm3

- Total bilirubin < 1.5 times upper limit of normal (ULN)

- Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) < 2.5 times the
ULN ( < 5 x ULN for patients with liver involvement)

- Creatinine < 1.5 times ULN

- Women of childbearing potential must have a negative serum pregnancy test performed
within 7 days prior to the start of treatment

- Women of childbearing potential and men must agree to use adequate contraception
(barrier method of birth control) prior to study entry and for the duration of study
participation. Men should use adequate birth control for at least three months after
the last administration of sorafenib.

- International normalized ratio (INR) < 1.5 or a Prothrombin Time / Partial
thromboplastin time (PT/PTT) within normal limits. Patients receiving
anti-coagulation treatment with an agent such as warfarin or heparin may be allowed
to participate. - For patients on warfarin, the INR should be measured prior to
initiation of sorafenib and monitored at least weekly, or as defined by the local
standard of care, until INR is stable.

Exclusion Criteria:

- Patients must not be candidates for potentially curative complete surgical resection
or definitive radiation. (Patients may have received prior chemotherapy as part of
definitive chemoradiotherapy and/or for recurrent/metastatic disease)

- Cardiac disease: Congestive heart failure > class II New York Heart Association
(NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new
onset angina (began within the last 3 months) or myocardial infarction within the
past 6 months.

- Known brain metastasis. Patients with neurological symptoms must undergo a CT
scan/MRI of the brain to exclude brain metastasis.

- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
pressure > 90 mmHg, despite optimal medical management.

- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.

- Active clinically serious infection > Common Terminology Criteria for Adverse events
(CTCAE) Grade 2.

- Thrombolic or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months.

- Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 (symptomatic and requiring
medical intervention) within 4 weeks of first dose of study drug.

- Any other hemorrhage/bleeding event > CTCAE Grade 3 (bleeding requiring blood
transfusion or intervention with endoscopy or surgery) within 4 weeks of first dose
of study drug.

- Serious non-healing wound, ulcer, or bone fracture.

- Evidence or history of bleeding diathesis or coagulopathy Major surgery, open biopsy
or significant traumatic injury within 4 weeks of first study drug.

- Use of St. John's Wort or rifampin (rifampicin).

- Known or suspected allergy to sorafenib or any agent given in the this trial.

- Any malabsorption problem.

- Previous therapy with cetuximab for the treatment of recurrent and/or metastatic
SCCHN. Previous therapy with cetuximab during definitive radiation therapy for
locally advanced SCCHN is permitted so long as relapse of SCCHN occurred at least > 6
months (180 days) from the end of cetuximab therapy.

- Previous therapy with sorafenib, sunitinib or another small molecule known to inhibit
the vascular endothelial growth factor receptors.