IRESSA™ (Gefitinib) With Cisplatin Plus Radiotherapy for the Treatment of Previously Untreated Unresected Late Stage III/IV Non-Metastatic Head and Neck Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The primary purpose of this study is to assess the effectiveness of ZD1839 250 mg and 500 mg when given either concomitantly or as maintenance to a standard therapy of radiotherapy (X-rays) plus chemotherapy (cisplatin) in terms of local disease control (progression-free) rate at 2 years.

Official Title
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A Phase 2 Randomised, Double-Blind, Placebo-Controlled, Multicentre Comparative Study of Gefitinib 250 mg or 500 mg (IRESSA™) Given Either Continuously or Concomitantly With Cisplatin Plus Radiotherapy for the Treatment of Patients With Previously Untreated Unresected Late Stage III/IV Non-Metastatic Head and Neck Squamous Cell Carcinoma

Conditions
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Neoplasms, Squamous Cell

Intervention / Treatment
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* Drug: gefitinib (Iressa)
* Drug: cisplatin
* Radiation: radiotherapy
* Drug: Gefitinib (Iressa)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed stage III or IVA squamous cell carcinoma of the head and neck No prior surgery or chemotherapy/biological therapy/radiation therapy Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Life expectancy of more than 12 weeks Exclusion Criteria: Cancers of the nasal space, oral cavity and larynx; or certain lung diseases. Abnormal blood chemistry; uncontrolled respiratory, cardiac, hepatic, or renal disease; or coexisting malignancies.

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: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Radiation + cisplatin; followed by placebo as maintenance therapy | Drug: cisplatin<br>* intravenous infusion<br>Radiation: radiotherapy<br>* radiation therapy<br>|
| Experimental: 2<br>250 mg gefitinib + radiation + cisplatin; followed by placebo as maintenance therapy | Drug: gefitinib (Iressa)<br>* 250 mg oral tablet<br>* Other names: IRESSA;Drug: cisplatin<br>* intravenous infusion<br>Radiation: radiotherapy<br>* radiation therapy<br>|
| Experimental: 3<br>500 mg gefitinib + radiation + cisplatin; followed by placebo as maintenance therapy | Drug: cisplatin<br>* intravenous infusion<br>Radiation: radiotherapy<br>* radiation therapy<br>Drug: Gefitinib (Iressa)<br>* 500 mg oral tablet<br>* Other names: Iressa;|
| Experimental: 4<br>gefitinib 250 mg + cisplatin + radiotherapy; followed by gefitinib 250 mg as maintenance therapy | Drug: gefitinib (Iressa)<br>* 250 mg oral tablet<br>* Other names: IRESSA;Drug: cisplatin<br>* intravenous infusion<br>Radiation: radiotherapy<br>* radiation therapy<br>|
| Experimental: 5<br>gefitinib 500 mg + cisplatin + radiotherapy; followed by gefitinib 500 mg as maintenance therapy | Drug: cisplatin<br>* intravenous infusion<br>Radiation: radiotherapy<br>* radiation therapy<br>Drug: Gefitinib (Iressa)<br>* 500 mg oral tablet<br>* Other names: Iressa;|
| Placebo Comparator: 6<br>placebo + cisplatin + radiotherapy; followed by gefitinib 250 mg as maintenance therapy | Drug: gefitinib (Iressa)<br>* 250 mg oral tablet<br>* Other names: IRESSA;Drug: cisplatin<br>* intravenous infusion<br>Radiation: radiotherapy<br>* radiation therapy<br>|
| Placebo Comparator: 7<br>placebo + cisplatin + radiotherapy; followed by gefitinib 500 mg as maintenance therapy | Drug: cisplatin<br>* intravenous infusion<br>Radiation: radiotherapy<br>* radiation therapy<br>Drug: Gefitinib (Iressa)<br>* 500 mg oral tablet<br>* Other names: Iressa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Disease Control Rate at 2 Years | A patient demonstrated local disease control at 2 years if there was no evidence of failure of treatment. Failure was defined as the patient having objective disease progression (as per RECIST) inside the original irradiated area, at an isodose level (between 20% and 95%), or death. | Assessed at 2 yrs. Tumour assessments (clinical & by CT/MRI) were carried out during screening & regularly throughout the study until disease progression (as defined by Response evaluation criteria in solid tumours (RECIST)). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Disease Control Rate at 1 Year | A patient demonstrated local disease control at 1 year if there was no evidence of failure of treatment. Failure was defined as the patient having objective disease progression (as per RECIST) inside the original irradiated area, at an isodose level (between 20% and 95%), or death. | Assessed after 1 year. Tumour assessments (clinical and by CT/MRI) were carried out during screening & regularly throughout the study until disease progression (as defined by RECIST). | 
| Complete Response | A patient was deemed to be a complete responder if the RECIST criteria for complete response were satisfied at any time during the study. | Assessed at 2 years. Clinical tumour assessments and tumour assessment by CT/MRI were carried out during screening and regularly throughout the study until disease progression. | 
| Tumour Response (Complete Response + Partial Response) | A patient was deemed to be have a tumour response if the RECIST criteria for complete response or partial response were satisfied at any time during the study. | Assessed at 2 years. Clinical tumour assessments and tumour assessment by CT/MRI were carried out during screening and regularly throughout the study until disease progression | 
| Progression Free Survival | Percentage of participants who are progression free at 2 years (calculated using the Kaplan-Meier method, which allows for censored observations for example those lost to follow-up). A patient is said to have progressed if they have progression of target or non-target lesions or evidence of any new lesions (as defined by RECIST). | Clinical tumour assessments and tumour assessment by CT/MRI were carried out during screening and regularly throughout the study until disease progression (as defined by RECIST) | 
| Overall Survival | Percentage of participants who are alive at 2 years (calculated using the Kaplan-Meier method, which allows for patients who do not have complete follow-up (censored observations)). | Overall survival assessed at 2 years | 
| Safety and Tolerability |  | Assessed over two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Squamous Cell Carcinoma, Head and Neck Squamous Cell Cancer, Squamous Cell Carcinoma, Squamous Cell Cancer