Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

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