A Phase I Trial of Concurrent Chemoradiation/Chemoreirradiation With Cetuximab (ERBITUX®), Sunitinib, and Accelerated Radiation in Patients With Locally Advanced/High-risk/Recurrent Poor Prognosis Head and Neck Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed squamous cell carcinoma of the head and
neck, meeting any of the following criteria:

- Recurrent disease

- Second primary locoregional recurrence* with no clinically measurable distant
disease

- Poor prognosis non-metastatic head and neck carcinoma (M0)

- Must have undergone radiotherapy as a component of prior treatment

- Not a candidate for surgical resection with curative intent

- Patients with high-risk features at resection or following resection for
recurrence are eligible

- Must have locoregional tumor amenable to radiotherapy or reirradiation with curative
intent

- Entire gross tumor recurrence volume must be able to be treated without
exceeding a cumulative spinal cord dose of 50 Gy

- Unresected tumors must be measurable according to RECIST

- No known brain metastases

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 12 weeks

- WBC ≥ 3,000/mm^³

- ANC > 1,500/mm³

- Platelet count > 100,000/mm³

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

- INR and PTT ratio < 1.5

- AST and ALT ≤ 2.5 times ULN

- Creatinine normal OR creatinine clearance > 60 mL/min

- Urine protein no more than trace

- Hematocrit ≥ 28%

- Hemoglobin ≥ 9 g/dL

- QTc < 500 msec

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- The following patients are eligible provided they have New York Heart Association
class II cardiac function on baseline ECHO and MUGA:

- Asymptomatic on treatment

- Prior anthracycline exposure

- Prior central thoracic radiotherapy included the heart in the radiotherapy port

- No clinical evidence of active infection of any type, including hepatitis B or C
virus

- Infections controlled with therapy are allowed

- Patients with hepatitis B or C on antiviral therapy with no detectable virus are
allowed

- No immune deficiency and/or HIV positivity

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to sunitinib malate

- No gastrointestinal tract disease or condition, including any of the following, that
impairs ability to retain sunitinib tablets:

- Inability to take oral medication or a requirement for IV alimentation

- Prior surgical procedures affecting absorption

- Active peptic ulcer disease

- None of the following conditions allowed:

- Serious or nonhealing wound, ulcer, or bone fracture

- Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within the past 28 days

- No significant concurrent medical or psychiatric illness which, in the opinion of the
investigator, would interfere with the patient's ability to participate in the trial

- No active carotid artery involvement

- No history of documented thrombosis (pulmonary embolism within the past 12 months or
deep vein thrombosis [DVT] within the past 6 months), known coagulopathies or
thrombophilia, or evidence of DVT/thromboembolic event

- No history of the following cardiovascular conditions :

- Myocardial infarction within the past 12 months

- Cardiac arrhythmia or serious ventricular arrhythmia (ventricular fibrillation
or ventricular tachycardia ≥ 3 beats in a row) within the past 12 months

- Stable/unstable angina within the past 12 months

- Symptomatic congestive heart failure within the past 12 months

- Coronary/peripheral artery bypass graft or stenting within the past 12 months

- No cerebral vascular disease, cerebrovascular accident (stroke), or transient
ischemic attack within the past 6 months

- QTc prolongation (QTc interval ≥ 500 msec)

- New York Heart Association class III-IV congestive heart failure

- Poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 140 mm Hg
or diastolic BP ≥ 90 mm Hg)

- Other significant ECG abnormalities

- See Disease Characteristics

- Recovered from all prior radiotherapy and chemotherapy

- More than 4 months since prior radiotherapy to the head and neck

- More than 2 weeks since prior hormone replacement therapy or hormonal contraceptives

- More than 4 weeks since prior and no other concurrent investigational agents

- At least 1 month since prior surgery (unless ambulatory within 48 hours)

- At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the
following:

- Azole antifungals (ketoconazole, itraconazole)

- Clarithromycin

- Erythromycin

- Diltiazem

- Verapamil

- HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir,
nelfinavir)

- Delavirdine

- At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the
following:

- Rifampin

- Rifabutin

- Carbamazepine

- Phenobarbital

- Phenytoin

- St. John wort

- Efavirenz

- Tipranavir

- Concurrent coumarin-derivative anticoagulants (e.g., warfarin up to 2 mg daily)
allowed for prophylaxis of thrombosis

- Concurrent use of medications known to affect the conductive system (e.g.,
beta-blockers, calcium channel blockers, or digoxin) allowed under investigator
supervision

- No concurrent agent with proarrhythmic potential, including any of the following:

- Terfenadine

- Quinidine

- Procainamide

- Disopyramide

- Sotalol

- Probucol

- Bepridil

- Haloperidol

- Risperidone

- Indapamide

- Flecainide

- No concurrent chronic steroid treatment for > 6 months (i.e., prednisolone doses > 10
mg/day or equivalent)

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent amifostine

- No concurrent commercial agent or therapy intended to treat head and neck cancer

- No other concurrent anticancer therapy