Sunitinib in Treating Patients With Recurrent and/or Metastatic Head and Neck Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well sunitinib works in treating patients with recurrent and/or metastatic head and neck cancer. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Detailed Description
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OBJECTIVES: I. Determine the overall response rate of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with sunitinib malate. II. Determine the toxicity of this drug in these patients. III. Determine the feasibility of administering this drug to patients with ECOG performance status 2 (cohort B). OUTLINE: This is a multicenter, cohort study. Patients are assigned to one of two cohorts according to ECOG performance status (ECOG 0-1 [cohort A] vs ECOG 2 [cohort B]). Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for at least 1 year.

Official Title
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Phase II Study of Sunitinib Malate in Head and Neck Squamous Cell Carcinoma

Conditions
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Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Oropharynx, Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

Intervention / Treatment
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* Drug: sunitinib malate


Participation Criteria
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Eligibility Criteria
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Criteria: Hemoglobin >= 9 g/dL Histologically or cytologically confirmed squamous cell carcinoma of the head and neck: Recurrent and/or metastatic disease Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques OR as >= 10 mm with spiral CT scan No known brain metastases Life expectancy >= 2 months ECOG performance status (PS) 0-1 or Karnofsky PS 70-100% (for patients in cohort A) ECOG PS 2 or Karnofsky PS 60-70% (for patients in cohort B) WBC >= 3,000/mm^3 Absolute neutrophil count >= 1,500/mm^3 Platelet count >= 100,000/mm^3 Calcium =< 12.0 mg/dL Bilirubin normal AST and ALT =< 2.5 times upper limit of normal Creatinine normal OR creatinine clearance >= 60 mL/min QTc < 500 msec No New York Heart Association class III or IV heart failure: Patients with the following are eligible provided they have New York Heart Association class II cardiac function on baseline ECHO/MUGA: History of class II heart failure and asymptomatic on treatment Prior anthracycline exposure Prior central thoracic radiation that included the heart in the radiotherapy port Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of allergic reactions to compounds of similar chemical or biological composition to sunitinib malate No history of serious ventricular arrhythmia (i.e., ventricular fibrillation or ventricular tachycardia >= 3 beats in a row) No history of other significant ECG abnormalities No uncontrolled hypertension (defined as systolic blood pressure [BP] >= 140 mm Hg or diastolic BP >= 90 mm Hg) No condition resulting in an inability to take oral medication, including any of the following: Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation Active peptic ulcer disease No gastrostomy, jejunostomy, or other forms of enteral tube-feeding modalities No serious or nonhealing wound, ulcer, or bone fracture No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days No cerebrovascular accident or transient ischemic attack within the past 12 months No myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within the past 12 months No pulmonary embolism within the past 12 months No pre-existing uncontrolled thyroid abnormality (i.e., inability to maintain thyroid function within the normal range with medication) No uncontrolled intercurrent illness, including either of the following: Ongoing or active infection Psychiatric illness or social situation that would limit compliance with study requirement No more than two prior regimens for recurrent or metastatic disease: Prior chemotherapy as part of initial curative intent therapy (e.g., neoadjuvant, adjuvant, or concurrent chemoradiotherapy) is allowed and will not count as prior therapy for recurrent or metastatic disease At least 4 weeks since prior major surgery At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered At least 4 weeks since prior radiotherapy No prior treatment with any other antiangiogenic agent (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, vatalanib, or VEGF Trap) No prior surgical procedure affecting absorption At least 7 days since prior and no concurrent use of CYP3A4 inhibitors, including any of the following: Azole antifungals (e.g., ketoconazole, itraconazole) Verapamil Clarithromycin HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, nelfinavir) Erythromycin Delavirdine Diltiazem At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the following: Rifampin Phenytoin Rifabutin Hypericum perforatum (St. John's wort) Carbamazepine Efavirenz Phenobarbital Tipranavir No concurrent therapeutic doses of coumarin-derivative anticoagulants (e.g., warfarin): Concurrent dosing of =< 2 mg of warfarin daily for prophylaxis of thrombosis is allowed; Concurrent low molecular weight heparin allowed provided prothrombin time INR is =< 1.5 No other concurrent investigational agents No concurrent agents with proarrhythmic potential, including any of the following: Terfenadine Quinidine Procainamide Disopyramide Sotalol Probucol Bepridil Haloperidol Risperidone Indapamide Flecainide No other concurrent anticancer agents or therapies No concurrent combination antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. | Drug: sunitinib malate<br>* Given orally<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response Rate (Complete Response [CR] and Partial Response [PR]) Using RECIST Criteria | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR | While patient remains on treatment, up to 30 weeks | 
| Feasibility of Treatment | Ability to remain on treatment without dose reduction | While patient remains on treatment, up to 30 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Time to disease progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Up to 2 years | 
| Overall Survival | Time from start of treatment until death from any cause. | Up to two years |