Fluorouracil, Hydroxyurea, Cetuximab and Twice-daily Intensity Radiation Therapy for Advanced Head and Neck Cancer

Study Overview
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Brief Summary
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For advanced head and neck cancer, combined radiation and chemotherapy prevents recurrences and for many patients, improves survival. While combined cisplatin and radiation or cetuximab and radiation is more effective than radiation alone, approximately 50% of these patients will still recur. A more aggressive approach may be needed for these patients to prevent recurrence and death. The strategy of using multiple chemotherapy drugs with radiation given twice a day has been tested at Mount Sinai and University of Chicago. Approximately 80% of patients are cured with this strategy. While cure rates are higher than standard chemotherapy and radiation and the treatment is tolerable, side effects during treatment are common. We propose replacing a chemotherapy drug with a less toxic, targeted therapy called cetuximab. Our goal is to reduce toxicity while maintaining or improving cure rates for these patients.

Official Title
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Phase II Study of Concomitant Fluorouracil, Hydroxyurea, Cetuximab and Hyperfractionated Intensity Modulated Radiation Therapy for Locally Advanced Head and Neck Cancer

Conditions
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Head and Neck Cancer, Cancer of the Pharynx, Cancer of the Larynx, Nose Neoplasms, Paranasal Sinus Neoplasms, Cancer of the Oral Cavity

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Hydroxyurea
* Drug: Fluorouracil
* Procedure: radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Histologically or cytologically confirmed diagnosis of squamous cell or poorly differentiated carcinomas of the head and neck or lymphoepithelioma No prior chemotherapy or radiotherapy Prior surgical therapy will consist only of incisional or excisional biopsy, and organ sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an existing primary tumor Karnofsky performance status of >= 70% Intact organ and bone marrow function Obtained informed consent Exclusion Criteria: Demonstration of metastatic disease (i.e. M1 disease). Patients with a history of severe allergic reaction to docetaxel or other drugs formulated with polysorbate 80. History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, 5-fluorouracil, or hydroxyurea. Other coexisting malignancies or malignancies diagnosed within the previous 3 years with the exception of basal cell carcinoma, cervical cancer in situ, and other treated malignancies with no evidence of disease for at least 3 years. Prior surgical therapy other than incisional or excisional biopsy and organ-sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an unknown primary tumor. Any non-biopsy procedure must have taken place less than 3 months from initiating protocol treatment. Incomplete healing from previous surgery Pregnancy or breast feeding (men and women of child-bearing potential are eligible but must consent to using effective contraception during therapy and for at least 3 months after completing therapy) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF are excluded. The exclusion of patients with active coronary artery disease will be at the discretion of the attending physician. Uncontrolled active infection unless curable with treatment of their cancer.

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: Advanced Head and Neck Cancer<br>Patients with stage IVA and IVB or high-risk stage III squamous cell carcinomas of the head and neck | Drug: Cetuximab<br>* 250 mg/m2 on Day 1 after the first dose of radiation was administered to all patients<br>Drug: Hydroxyurea<br>* 500 mg orally every 12 hours with the morning dose administered 2 hours before radiation<br>Drug: Fluorouracil<br>* continuous-infusion 5-FU at a dose of 600 mg/m2 daily for 120 hours<br>Procedure: radiotherapy<br>* Radiotherapy was administered at 1.5 Gy per fraction twice daily with treatments separated by at least 6 hours on Days 1 through 5 on an alternating week schedule. Radiation was delivered with intensity-modulated radiation therapy (IMRT) planning for all patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Llocoregional Recurrence | Percentage of Participants with Loco-regional recurrence. | 2 years | 
| Survival | Overall Survival - Percentage of Participants who survived Disease-Free Survival - measured from the initiation of nonsurgical treatment to either the last follow-up, disease progression, or death using intent-to-treat methodology | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long- Term Toxicity | Grade 3 toxicities events | 2 years | 
| UW-QOLR: Quality of Life Score | University of Washington Quality of Life (UW-QOLR) questionnaire - covers 12 domains - pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder function, taste, saliva, mood and anxiety. Each domain have between 3 and 6 response options that are scaled evenly from 0 (worst) to 100 (best) according to the hierarchy of response and reported as one composite score from 0 (worst) to 100 (best). | 2 years | 
| Distant Metastases | Percentage of participants who did not have distant control | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer of the Nasal Cavity