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