Cisplatin, Fluorouracil, Iressa, and Radiation Therapy Patients With 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 cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cisplatin, fluorouracil, and gefitinib together with radiation therapy may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects of giving cisplatin, fluorouracil, and gefitinib together with hyperfractionated radiation therapy and to see how well they work in treating patients with locally advanced head and neck cancer.

Detailed Description
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OBJECTIVES: Primary Explore the activity of cisplatin, fluorouracil, gefitinib, and hyperfractionated radiotherapy, in terms of 1-year survival and 1-year distant metastatic disease control, in patients with locally advanced squamous cell carcinoma of the head and neck. Secondary Explore the activity of this regimen, in terms of disease-specific survival and local control, in these patients. Assess the toxicity of this regimen in these patients. Assess the complete response rate in patients treated with this regimen. Assess the toxicity and tolerability of long-term maintenance with gefitinib in patients rendered disease free after this treatment regimen. OUTLINE: Patients undergo hyperfractionated radiotherapy twice daily, 5 days a week, beginning on day 1 and continuing for 6 weeks. Patients also receive fluorouracil IV continuously over 96 hours and cisplatin IV continuously over 96 hours on days 1-4 and 22-25 and oral gefitinib beginning once daily on day 1 and continuing for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3-6 months. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Official Title
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A Phase I/II Trial of Concurrent Chemotherapy and ZD1839 (IRESSA) With Hyperfractionated Radiation Therapy, Followed by Maintenance ZD1839 (IRESSA) for Patients With Locally Advanced Squamous Cell Head and Neck Cancer

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: fluorouracil
* Drug: Iressa
* Radiation: hyperfractionated radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed primary* squamous cell carcinoma of the head and neck region, excluding any of the following: Nasopharynx Paranasal sinuses Salivary glands NOTE: *Primary site must be identified Locoregionally confined stage III or IV disease No evidence of nodal disease below the clavicles No distant hematogenous metastases (M0) PATIENT CHARACTERISTICS: ECOG performance status 0-1 WBC > 3,500/mm³ Platelet count > 100,000/mm³ Creatinine ≤ 2.0 mg/dL Alkaline phosphatase < 2 times normal AST < 2 times normal Bilirubin ≤ 2.0 mg/dL Calcium normal Not pregnant or nursing Fertile patients must use effective contraception Must not be a poor compliance risk for follow-up No known severe hypersensitivity to gefitinib or any excipients of this drug No evidence of clinically active interstitial lung disease Patients with chronic, stable radiographic changes who are asymptomatic are eligible No unstable or uncontrolled angina, clinically apparent jaundice, or active infection No history of any other malignancy (except squamous cell or basal cell skin cancer or cervical carcinoma in situ) unless disease free for ≥ 5 years No other severe, uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) PRIOR CONCURRENT THERAPY: Recovered from prior oncologic or other major surgery No prior definitive surgery, radiotherapy, chemotherapy, immunotherapy, or epidermal growth factor receptor inhibitors for head and neck cancer No investigational drugs within the past 30 days No concurrent CYP3A4 inducers, including any of the following: Phenytoin Carbamazepine Rifampin Phenobarbital Hypericum perforatum (St. John's wort) Concurrent surgery allowed provided gefitinib is not administered 2 weeks before and 2 weeks after surgery No concurrent aminoglycoside antibiotics

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concurrent Chemotherapy and ZD1839<br> | Drug: cisplatin<br>* 20mg/m2/d IV continuous infusion x4 days<br>* Other names: CDDP;Drug: fluorouracil<br>* 1000mg.m2/d IV continuous x 4 days<br>* Other names: 5FU;Drug: Iressa<br>* 250mg/PO qd x 2 years<br>* Other names: ZD1839;Radiation: hyperfractionated radiation therapy<br>* 120cGy bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Treated With ZD1839 With Chemotherapy and Hyperfractionated Radiation That Had a 1-year Survival | To explore the activity of ZD1839 with chemotherapy and hyperfractionated radiation using 1-year survival | at 1 year after start of treatment | 
| Number of Participants With No Distant Metastatic Disease at 1 Year | 1-year distant metastatic disease control in patients with locally advanced squamous cell head and neck cancer. Distant disease means that cancer came back in sites outside of the head and neck. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With No Local Disease at 1 Year | Number of Participants with No Local Disease at 1 Year. Local disease means that the cancer came back in the same site. | at 1 year after start of treatment | 
| Number of Patients With Greater Than or Equal to Mild (Grade 1) Toxicity | Any toxicity greater than or equal to Grade 1= mild | at 1 year after start of treatment | 
| Number of Patients With a Complete Response Defined as Complete Disappearance of All Clinically Detectable Tumor. | Complete response rate per RECIST Criteria (CTC V3) | 3 years | 
| Number of Participants Who Completed 2 Years of Therapy |  | at 2 years after start of treatment | 

 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 oropharynx, stage IV squamous cell carcinoma of the oropharynx