Sorafenib in Combination With Carboplatin and Paclitaxel in Treating Participants With Metastatic or Recurrent Head and Neck Squamous Cell Cancer

PRIMARY OBJECTIVES:

I. To evaluate the progression free survival of the combination of sorafenib (BAY 43-9006),
carboplatin, and paclitaxel in patients with recurrent or metastatic squamous cell cancer of
the head and neck (SCCHN).

SECONDARY OBJECTIVES:

I. Response rate, toxicity, safety profile, exploratory biomarker data, and overall survival.

OUTLINE:

Participants receive carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over 3
hours on day 1, and sorafenib orally (PO) twice daily (BID) on days 2-19. Treatment repeats
every 21 days for up to 6 courses. Starting with course 7, participants receive sorafenib PO
daily in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up between 21-35 days.

Inclusion Criteria:

- Ability to understand and the willingness to sign a written informed consent. A signed
informed consent must be obtained prior to any study specific procedures.

- Patients must have cytologically or histologically proven recurrent or metastatic
squamous cell cancer of the head and neck (SCCHN) from the primary tumor or lymph
nodes of the oral cavity, larynx, oropharynx, or hypopharynx.

- No prior systemic chemotherapy for patients who present with metastatic disease. For
patients with recurrent head and neck squamous cell carcinoma, prior chemotherapy is
allowed if it was given as part of their definitive therapy. If patients have received
prior combined modality therapy, they must be off therapy for at least 6 months.

- Patients must have at least 1 evaluable lesion. Lesions must be evaluated by computed
Tomography (CT) scan or magnetic resonance imaging (MRI).

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

- Controlled blood pressure (defined as systolic blood pressure [BP] =< 140 mmHg and
diastolic =< 85 mmHg).

- Hemoglobin >= 9.0 g/dL within 7 days prior to start of first dose.

- Absolute neutrophil count (ANC) >= 1,500/mm^3 within 7 days prior to start of first
dose.

- Platelet count >= 100,000/mm^3 within 7 days prior to start of first dose.

- Total bilirubin =< 1.5 times the upper limit of normal (ULN) within 7 days prior to
start of first dose.

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5
x ULN for patients [pts] with [w/] liver involvement) within 7 days prior to start of
first dose.

- International normalized ratio (INR) =< 1.5 and partial thromboplastin time (PTT)
within (w/in) normal limits within 7 days prior to start of first dose.

- Serum creatinine =< 1.5 ULN or creatinine clearance (CrCl) >= 45 mL/min for patients
(pts) w/ creatinine levels above institutional normal within 7 days prior to start of
first dose.

- Amylase & lipase < 1.5 x the ULN within 7 days prior to start of first dose.

- Urinalysis (UA) must show less than 1+ protein in urine, or the pt will require a
repeat UA. If repeat UA shows 1+ protein or more, a 24 hour urine collection will be
required & must show total protein =< 1000 mg/24 hour to be eligible.

- Women of childbearing potential (not surgically sterilized or at least 2 years
postmenopausal) must have a negative serum or urine pregnancy test performed within 7
days prior to the start of treatment.

- Women of childbearing potential and men must agree to use adequate contraception
(abstinence; hormonal or barrier method of birth control) prior to study entry, for
the duration of study participation and 3 months after end of treatment. Should a
woman become pregnant while participating or the partner of a patient participating in
this study becomes pregnant, they should inform their treating physician immediately.

Exclusion Criteria:

- Congestive heart failure (CHF) > class II New York Heart Association (NYHA); active
coronary artery disease (myocardial infarction [MI] more than 6 months prior to study
entry is allowed); or serious cardiac ventricular arrhythmias requiring
anti-arrhythmic therapy (beta blockers or digoxin are permitted).

- Uncontrolled hypertension defined as systolic blood pressure > 140 mmHg or diastolic
pressure > 85 mmHg despite optimal medical management.

- Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B
or C.

- Active clinically serious infections (i.e. patients currently taking antibiotics)
(grade 2 National Cancer Institute [NCI]-Common Terminology Criteria for Adverse
Events (CTCAE) version 3.0).

- Evidence or history of central nervous system (CNS) disease, including primary brain
tumors, seizures disorders, or any brain metastasis.

- Thrombotic or embolic events such as cerebrovascular accident, deep vein thrombosis or
pulmonary embolism. History of transient ischemic attack is allowed.

- Evidence or history of bleeding diathesis or coagulopathy.

- History of/or current evidence of hemoptysis (bright red blood of ½ teaspoon or more).

- Peripheral neuropathy >= grade 2 (NCI-CTC version 3.0).

- Anticancer chemotherapy or immunotherapy: anticancer therapy is defined as any agent
or combination of agents with clinically proven anticancer activity administered by
any route with the purpose of affecting the cancer, either directly or indirectly,
including palliative and therapeutic endpoints.

- Radiotherapy to the target lesions within 3 weeks of start of first dose. Toxicities
from radiotherapy must have resolved prior to start of first dose.

- No major surgery, open biopsy or significant traumatic injury within 4 weeks of start
of first dose.

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

- Granulocyte growth factors (G-CSF), within 3 weeks of study entry.

- Patients taking chronic erythropoietin are permitted provided no dose adjustment is
made within 2 months prior to start of first dose.

- Pregnant or breastfeeding patients.

- Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results.

- Known or suspected allergy to any recombinant human antibodies, or compounds of
similar chemical or biologic composition to sorafenib or any of the drugs in this
study.

- Any condition that is unstable or could jeopardize the safety or compliance of the
patient in the study.

- Previous or concurrent cancer that is distinct in primary site or histology from the
cancer being evaluated in the study EXCEPT cervical cancer in situ, treated basal cell
carcinoma, superficial bladder tumors (Ta, Tis and T1) or any cancer curatively
treated > 3 years prior to study entry.

- Known or suspected allergy to sorafenib (BAY 43-9006) or any agent given in
association with this trial.

- Any malabsorption conditions.

- Therapeutic anticoagulation with warfarin, heparins, or heparinoids.

- Patients taking phenytoin, carbamazepine, and phenobarbital.

- Patients taking rifampin and/or St. John's Wort.

- Patients who are candidates for curative surgery or radiotherapy.

- The patient has progressed within 6 months after completion of curative intent
(definitive) treatment for localized/locoregionally advanced disease.