Nab-Paclitaxel, Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: 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. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cetuximab and cisplatin together with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cetuximab and cisplatin together with radiation therapy works in treating patients with recurrent head and neck cancer.

Detailed Description
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OBJECTIVES: Primary To evaluate whether treatment with cetuximab, cisplatin, and intensity-modulated radiotherapy improves the overall survival of patients with recurrent squamous cell carcinoma of the head and neck. Secondary To determine the progression-free survival and local-regional progression in these patients. To identify and estimate the incidence rate of acute and late toxicities associated with this treatment regimen. To determine the pattern of disease progression in these patients. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 60-120 minutes once weekly in weeks 1-7. Patients also receive cisplatin IV over 60 minutes once weekly and undergo intensity-modulated radiotherapy once daily 5 days a week in weeks 2-7. 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 II Multi-Center Study of Concomitant Cetuximab and Cisplatin With Re-Irradiation Using Intensity-Modulated Radiotherapy in Patients With Recurrent Squamous Cell Carcinoma of the Head-and-Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: cetuximab
* Drug: cisplatin
* Radiation: intensity-modulated radiation therapy
* Drug: Nab-Paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Pathologically confirmed squamous cell carcinoma (SCC) of the upper aerodigestive tract Recurrent disease or second primary SCC Recurrence or second primary must be confined to the head and neck above the clavicles (loco-regional recurrence) Majority (≥ 75%) of the recurrent tumor must be in areas previously irradiated to ≥ 45 Gy More than one recurrence allowed provided the first recurrence occurred > 6 months after the completion of prior radiotherapy Unresectable disease OR has high-risk features after resection (e.g., positive margins and/or extracapsular extension) No signs of carotid exposure No primary nasopharyngeal or salivary gland tumor Equivocal pulmonary nodes on chest CT scan allowed provided they are < 1 cm, cannot be safely biopsied, or are negative on PET scan No distant metastasis PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% ANC ≥ 2,000/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed) Bilirubin < 1.5 mg/dL AST or ALT < 2 times upper limit of normal Creatinine clearance ≥ 50 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to submit prior radiotherapy records to assure that the spinal cord tolerance is not exceeded No active cardiac disease, including 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 At least 3 heart-related hospitalizations within the past year No severe chronic obstructive pulmonary disease requiring ≥ 3 hospitalizations within the past year No concurrent medical illness that would impair patient tolerance to therapy or limit survival No other invasive malignancy within the past 2 years No pre-existing peripheral sensory neuropathy ≥ grade 2 No prior severe infusion reaction to a monoclonal antibody No prisoners or individuals who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from prior surgery Prior cisplatin and cetuximab allowed At least 6 months since prior radiotherapy or chemotherapy No prior radiotherapy > 75 Gy No prior chemotherapy for recurrent head and neck cancer Prior chemotherapy as a component of the primary treatment allowed No prior combination cisplatin, cetuximab, and radiotherapy for recurrent head and neck cancer Patients with a new primary head and neck cancer whose prior primary head and neck cancer was treated with concurrent cisplatin, cetuximab, and radiotherapy are eligible provided it has been > 6 months since treatment

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: Single Arm: Chemotherapy with Concurrent Radiation therapy<br>Nab-Paclitaxel, Cetuximab, Cisplatin, and Radiation Therapy intensity-modulated radiation therapy | Drug: cetuximab<br>* cetuximab<br>* Other names: chemo;Drug: cisplatin<br>* cisplatin<br>* Other names: chemo;Radiation: intensity-modulated radiation therapy<br>* IMRT<br>* Other names: IMRT;Drug: Nab-Paclitaxel<br>* Nab-Paclitaxel<br>* Other names: chemo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | The 2-year PFS was measured from the date of enrollment to the first occurrence of new metastatic lesions, objective tumor progression, or death. The combination of cisplatin and cetuximab concurrent with radiation therapy for head and neck cancer has shown to have a favorable PFS. Patients were followed until death or from 7.5 months to 63.6 months (median 25.6 months) in those alive at last evaluation. | 2 year from the date of enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Acute and Late Toxicities | Incidence rate of acute and late toxicities of grade 3 or higher was measured after each treatment cycle was over. The most common late toxicities defined as toxicity occurring more than 90 days after treatment included laryngeal edema and xerostomia. | 6 months within the end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent hypopharynx Cancer, recurrent larynx Cancer, recurrent verrucous carcinoma, squamous cell carcinoma, recurrent oral cavity cancer, recurrent metastatic occult primary cancer, recurrent oropharynx cacner, recurrent paranasal sinus and nasal cavity cancer, tongue cancer