Nab-Paclitaxel, Cisplatin, and Cetuximab With Concurrent Radiation Therapy for Locally Advanced Head and Neck Cancer

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of paclitaxel albumin-stabilized nanoparticle formulation when combined with cisplatin, cetuximab, and radiotherapy in patients with local-regionally advanced squamous cell carcinoma of the head and neck. (Phase I)
• To evaluate the disease-free survival of patients treated with this regimen. (Phase II)

Secondary

• To identify dose-limiting toxicities in these patients treated with this regimen. (Phase I)
• To assess the safety and tolerability of this regimen. (Phases I and II)
• To assess progression-free survival and survival of patients treated with this regimen. (Phase I)
• To assess overall survival in patients treated with this regimen. (Phase II)
• To assess response rates in patients treated with this regimen. (Phases I and II)

OUTLINE: This is a multicenter, phase I dose-escalation study of paclitaxel albumin-stabilized nanoparticle formulation followed by a phase II study.

Patients receive cetuximab IV over 120 minutes in week 1. Patients then receive cetuximab IV over 60 minutes, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes, and cisplatin IV over 60 minutes once weekly in weeks 2-8. Patients also undergo 3D conformal or intensity-modulated radiotherapy over 30 minutes on days 1-5 in weeks 2-8.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 4 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the oropharynx, hypopharynx, or larynx

• Diagnosis based on the primary lesion and/or lymph nodes
• Stage III or IV disease (T2, N2-3, M0 or T3-4, any N, M0)
• No primary tumor of the oral cavity, nasopharynx, sinuses, or salivary glands
• No distant metastasis by chest x-ray, CT scan, or PET/CT scan within the past 6 weeks

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• ANC > 1,500/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin > 9.0 g/dL (transfusion or other intervention to achieve hemoglobin > 8.0 g/dL allowed)
• Bilirubin ≤ 1.5 mg/dL
• AST, ALT, and AP ≤ 2.5 times upper limit of normal
• Serum creatinine ≤ 1.5 mg/dL
• Creatinine clearance ≥ 50 mL/min
• None of the following electrolyte abnormalities grade 3-4 by CTCAE v 3.0:

• Calcium < 7 mg/dL or > 12.5 mg/dL
• Glucose < 40 mg/dL or > 250 mg/dL
• Magnesium < 0.9 mg/dL or > 3 mg/dL
• Potassium < 3 mmol/L or > 6 mmol/L
• Sodium < 130 mmol/L or > 155 mmol/L
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other prior invasive malignancy, except for nonmelanomatous skin cancer, unless disease-free for ≥ 3 years
• No prior allergic reaction to study drugs
• No active cardiac disease, defined as any of the following:

• Unstable angina
• Uncontrolled hypertension
• Myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass graft or percutaneous transluminal coronary angioplasty)
• Uncontrolled arrhythmia
• Congestive heart failure
• Three or more heart-related hospitalizations within the past year
• No severe chronic obstructive pulmonary disease requiring ≥ 3 hospitalizations within the past year
• No AIDS
• No pre-existing peripheral sensory neuropathy ≥ grade 2
• No concurrent medical illnesses that would impair patient tolerance to therapy or limit survival

PRIOR CONCURRENT THERAPY:

• No prior systemic chemotherapy for this cancer

• Prior systemic chemotherapy for a different cancer allowed
• No prior radiotherapy to the region of this cancer that would result in overlap of radiotherapy fields
• No prior initial surgical treatment (excluding diagnostic biopsy of the primary site or nodal sampling of neck disease)
• At least 48 hours since prior and no concurrent granulocytic growth factors (e.g., filgrastim [G-CSF]) during radiotherapy
• No concurrent erythropoietic growth factors (e.g., darbepoetin, erythropoietin)