Trial of Induction Chemotherapy With Carboplatin and Paclitaxel, Followed by Concurrent Chemotherapy/Radiation Therapy With ZD1839 (IRESSA), 5-FU, Hydroxyurea, and Twice-Daily Radiation, Followed by Adjuvant ZD1839 Monotherapy in Patients With Locally Advanced Head & Neck Cancer

Study Overview
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Brief Summary
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The purpose of this study is to explore the activity of ZD1839 added to concurrent chemoradiotherapy and as adjuvant monotherapy in patients with locally advanced head and neck cancer. Activity is described in terms of response rate (complete responses only).

Official Title
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Ph II Trial of Induction Chemotherapy With Carboplatin and Paclitaxel, Followed by Concurrent Chemotherapy/Radiation Therapy With ZD1839 (IRESSA), 5-FU, Hydroxyurea, and Twice-Daily Radiation, Followed by Adjuvant ZD1839 Monotherapy in Patients With Locally Advanced Head & Neck Cancer

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: ZD 1839 500mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of squamous cell or poorly differentiated carcinomas, or lymphoepithelioma of the nasopharynx. Age 18 years or older. Patients with AJCC (6th edition, 2002) stage III or IV head and neck cancer. Patients with AJCC (6th edition, 2002) stage IV head and neck cancer. presenting with cervical lymph node metastasis of an unknown primary (i.e., TxN2 or TxN3) are also eligible. Prior to entry in the study, the resectability and alternative treatment options for each patient will be determined by a team composed of a head and neck surgeon, a radiation oncologist,and a medical oncologist. Stage determination, optimal local treatment, and its timing according to this protocol will be determined at this evaluation. Each patient will be classified as having resectable or unresectable disease. The unequivocal demonstration of distant metastasis (M1) confers ineligibility. Unidimensionally measurable disease (based on RECIST) is desirable but not strictly required. Individuals who are disease free at baseline after excisional biopsy or node dissection will be considered not evaluable for response assessment but are eligible. No prior 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 unknown primary tumor. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%. Patients must have normal organ and marrow function as defined below absolute neutrophil count (ANC) ≥ 1,500/μl platelets ≥ 100,000/μl total bilirubin within normal institutional limits aspartate aminotransferase (AST, SGOT)/ alanine aminotransferase (ALT, SGPT) ≤ 2.5 × institutional upper limit of normal alkaline phosphatase ≤ 2 × upper limit of normal creatinine within normal institutional limits Exclusion Criteria: Unequivocal demonstration of metastatic disease (i.e. M1 disease). Known severe hypersensitivity to ZD1839 or any of the excipients of this product. Any coexisting malignancy that would increase risk of toxicity, interfere with interpretation of toxicity, or is associated with a median survival of less than 24 months. Concomitant use of phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, or St.John's Wort. Treatment with an investigational drug within 30 days before Day 1 of trial treatment. Incomplete healing from previous surgery. Pregnancy or breast feeding (women of child-bearing potential). Patients should be advised to use effective contraception as appropriate. History of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel, Cremophor EL, carboplatin, 5 FU, or hydroxyurea. 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. Patients must have no uncontrolled active infection other than that not curable without treatment of their cancer. No patients with severe baseline neurologic deficits (> grade II neuropathy) will be treated with induction chemotherapy. Any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded.

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: ZD1839 500mg by mouth (po) daily<br>Single arm, two-stage, phase II trial of induction therapy with carboplatin and paclitaxel, followed by ZD1839, 5-FU, hydroxyurea, and hyperfractionated radiotherapy, followed by adjuvant ZD1839 alone. | Drug: ZD 1839 500mg<br>* Optional Induction chemotherapy: Carboplatin and paclitaxel combination will be administered for 2 cycles of 4 weeks duration each. Paclitaxel: 100 mg/m2 in 500 ml of dextrose 5% in water over 3hrs. Carboplatin: Start after completion of paclitaxel on Day 1 AUC 6 (creatinine clearance [CC] + 25). Administered in 100 ml of normal saline over 30min after completion of paclitaxel. Resume chemotherapy C2 on D29. ZD1839: 500mg PO QD from D1 of C1 of chemoradiotherapy, uninterrupted until disease progression. Chemotherapy should be administered during all 5 weeks of radiotherapy. P.M.:Start hydroxyurea at 500 mg PO q 12hrs × 6 days. The first daily dose of hydroxyurea on Days 1 through 5 is given 2 hours prior to the first fraction of daily radiotherapy. P.M.:Start continuous infusion of 5-FU at 600 mg/m2/day × 5D. Days 1 through 5: Radiation therapy is administered twice daily at 150 cGy ZD1839 will be administered from day 1 to 14 of every chemoradiotherapy cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate Achieved 1 Month After Concurrent Chemotherapy and Radiation Treatment | To explore the activity of ZD1839 added to concurrent chemoradiotherapy and as adjuvant monotherapy in patients with locally advanced head and neck cancer. Activity is described in terms of response rate (complete responses only). | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4 Year Overall Survival | Percentage of patients who survived 4 years or more | 0.3 to 4.7 years | 
| 4 Year Progression Free Survival | Percentage of patients who survived without progressive disease 4 years or more | 0.3 to 4.7 years | 
| 4 Year Disease Specific Survival | Percentage of patients who did not die by the disease within 4 years | 0.3 to 4.7 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lip, Larynx, Oral Cavity and Pharynx