Bevacizumab, Docetaxel, and Radiation Therapy in Treating Patients With Stage III or Stage IV Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as bevacizumab, 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, 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 bevacizumab together with docetaxel and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with docetaxel and radiation therapy works in treating patients with stage III or stage IV head and neck cancer.

Detailed Description
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OBJECTIVES: Primary Determine the time to progression in patients with stage III or IV squamous cell carcinoma of the head and neck treated with bevacizumab in combination with docetaxel and radiotherapy. Secondary Compare the objective response rate, locoregional control rate, duration of response, patterns of failure, and overall survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. OUTLINE: Patients undergo radiotherapy once daily, 5 days a week, for 8 weeks and receive docetaxel IV over 1 hour once a week for 8 weeks. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks for up to 1 year. Approximately 8-10 weeks after the completion of chemoradiotherapy, patients may undergo neck dissection. Bevacizumab, which stops 8 weeks before surgery, may restart 4 weeks after surgery and continue for 9 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Official Title
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A Phase II Study of Bevacizumab in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: docetaxel
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed squamous cell carcinoma of the head and neck Stage III or IV disease No evidence of distant metastases No salivary gland or paranasal sinus squamous cell carcinoma No disease with close proximity to a major vessel Measurable disease No known CNS or brain metastases Patients with intracranial extension without cerebral involvement may be eligible PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy > 12 weeks Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL Bilirubin normal AST and ALT ≤ 2 times upper limit of normal PT normal Creatinine normal OR Creatinine clearance ≥ 60 mL/min Urine protein: creatinine ratio < 1.0 No bleeding diathesis or coagulopathy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drugs No pre-existing peripheral neuropathy ≥ grade 2 No ongoing or active infection No serious non-healing wound, ulcer, or bone fracture No New York Heart Association class II-IV congestive heart failure No significant arrhythmias requiring medication No myocardial infarction within the past 6 months No stroke within the past 6 months No symptomatic coronary artery disease No second- or third-degree heart block or bundle branch block No unstable angina pectoris No hypertension (i.e., blood pressure ≥ 150/100 mm Hg) No other clinically significant heart disease No significant traumatic injury within the past 4 weeks No psychiatric illness or social situation that would preclude study compliance No HIV positivity No other malignancy within the past 5 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix No other uncontrolled illness No poorly compliant patients PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy No prior investigational anticancer agents More than 4 weeks since prior major surgery More than 1 week since prior minor surgery, fine-needle aspiration, or core needle biopsy No concurrent major surgery except planned neck dissection No concurrent routine colony-stimulating factor therapy No other concurrent investigational agents No other concurrent anticancer therapy

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: bevacizumab with docetaxel and radiation therapy<br> | Biological: bevacizumab<br>* Bevacizumab IV over 30-90 minutes once every 2 weeks for up to 1 year. Bevacizumab, which stops 8 weeks before surgery, may restart 4 weeks after surgery and continue for 9 months in the absence of disease progression or unacceptable toxicity.<br>Drug: docetaxel<br>* docetaxel IV over 1 hour once a week for 8 weeks<br>Procedure: conventional surgery<br>* 8-10 weeks after the completion of chemoradiotherapy, patients may undergo neck dissection<br>Radiation: radiation therapy<br>* radiotherapy once daily, 5 days a week, for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | The time to disease progression is calculated from the date of treatment. Data for patients who remain disease progression free are censored as of date when the last follow-up information is obtained. | 5 yrs after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST). A response will be determined by at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD | 5 years | 

 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 hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx