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