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

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. Paclitaxel albumin-stabilized nanoparticle formulation may make tumor cells more sensitive to radiation therapy. Giving radiation therapy and paclitaxel albumin-stabilized nanoparticle formulation together with cisplatin and cetuximab may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of paclitaxel albumin-stabilized nanoparticle formulation when given together with cisplatin, cetuximab, and radiation therapy to see how well they work in treating patients with locally advanced stage III or stage IV head and neck cancer.

Detailed Description
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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.

Official Title
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A Phase I/II Study of Nab-paclitaxel, Cisplatin and Cetuximab With Concurrent Radiation Therapy for Local-regionally Advanced Head-and-neck Squamous Cell Carcinoma

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: Cetuximab
* Drug: Cisplatin
* Drug: Nab-Paclitaxel
* Radiation: intensity-modulated radiation therapy


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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 one<br>Nab-Paclitaxel, Cisplatin, Cetuximab, intensity-modulated radiation therapy | Biological: Cetuximab<br>* Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor<br>Drug: Cisplatin<br>* Cisplatin is an anti-cancer chemotherapy drug<br>* Other names: Platinol;Drug: Nab-Paclitaxel<br>* paclitaxel albumin-stabilized nanoparticle formulation<br>* Other names: Abraxane;Radiation: intensity-modulated radiation therapy<br>* intensity-modulated radiation therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I Maximum Tolerated Dose of Nab-Paclitaxel | Seven participants were assigned nab-paclitaxel in dose of 25mg/m^2. Five participants were assigned nab-paclitaxel in dose of 20mg/m^2. | 90 days | 
| Phase II 2-year Progression-free Survival | 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. The primary endpoint of 2-year progression-free survival was measured from the date of enrollment to the first occurrence of new metastatic lesion, objective tumor progression, or death. | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II 2-year Local Control | Local control is defined as the arrest cancer growth at the site of origin. 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 | 2 year | 
| Phase II 2-year Overall Survival | median follow-up 24 months for 34 patients | 2 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage II squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, tongue cancer