Gefitinib as First-Line Therapy Followed by Gemcitabine and Cisplatin in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving gefitinib as first-line therapy followed by gemcitabine and cisplatin after disease progression may be an effective treatment for non-small cell lung cancer. PURPOSE: This phase II trial is studying how well gefitinib works as first-line therapy followed by gemcitabine and cisplatin in treating patients with stage III or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the efficacy of gefitinib as first-line therapy, in terms of response rate (complete and partial response) or stability of disease, in patients with de novo or recurrent stage IIIB or IV non-small cell lung cancer. Secondary Determine the safety of this drug in these patients. Determine the efficacy of gemcitabine combined with cisplatin when administered after first-line gefitinib in these patients. Determine quality of life of patients treated with this regimen. OUTLINE: This is an open-label, multicenter study. Patients receive oral gefitinib once daily until disease progression or unacceptable toxicity. Within 3 weeks after documented disease progression, patients receive gemcitabine IV over 30 minutes on days 1 and 8 followed by cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, weeks 3, 6, 12, 18, and then every 12 weeks thereafter during gefitinib treatment. During chemotherapy, quality of life is assessed 1 week prior to starting chemotherapy treatment, day 1 of courses 3 and 5, and then every 12 weeks until disease progression. After completion of study therapy, patients are followed every 3 months. PROJECTED ACCRUAL: 'A total of 24-63 patients will be accrued for this study.

Official Title
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Multicenter Phase II Trial of Gefitinib (Iressa™) First Line Therapy Followed by Chemotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: gefitinib
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically* or cytologically* confirmed non-small cell lung cancer (NSCLC), including any of the following cellular subtypes: Squamous cell carcinoma Adenocarcinoma Large cell carcinoma Poorly differentiated NSCLC NOTE: *New biopsies or cytologic specimens required for primary resection specimens older than 2 years De novo or recurrent disease, meeting 1 of the following stage criteria: Stage IIIB disease Malignant pleural effusion OR supraclavicular node involvement (N3) Not suitable for curative multimodal treatment or surgery Stage IV disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan or MRI Measurable lesion must be outside previously irradiated areas Immediate chemotherapy is not clinically mandatory No small cell lung cancer (SCLC) or SCLC combined with NSCLC No symptomatic and/or untreated brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status WHO 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10.0 g/dL Hepatic Bilirubin normal AST or ALT ≤ 2.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN in the presence of bone metastases) No unstable or uncompensated hepatic disease Renal Creatinine clearance > 60 mL/min No unstable or uncompensated renal disease Cardiovascular No unstable or uncompensated cardiac disease No myocardial infarction within the past 3 months Pulmonary No clinically active interstitial lung disease Asymptomatic patients with chronic stable radiographic changes allowed No unstable or uncompensated respiratory disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 12 months after completion of study treatment Able to swallow and retain oral medication No active infection No uncontrolled diabetes mellitus No history of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biological composition to study drugs No other severe or uncontrolled systemic disease No other serious underlying medical condition that would preclude study participation No psychiatric disability that would preclude study compliance or giving informed consent No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Prior intrapleural or intrapericardial local chemotherapy allowed No prior chemotherapy for advanced disease More than 6 months since prior neoadjuvant or adjuvant systemic chemotherapy for NSCLC Endocrine therapy Not specified Radiotherapy See Disease Characteristics Concurrent palliative radiotherapy allowed (except to brain metastases) Surgery Not specified Other No prior epidermal growth factor receptor-targeted therapy for NSCLC No concurrent use of any of the following CYP3A4 inducers: Phenytoin Carbamazepine Rifampin Barbiturates Hypericum perforatum (St. John's wort) More than 30 days since prior participation in another clinical trial No other concurrent investigational agent

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

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: gefitinib|nan|
|Drug: gemcitabine hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease stabilization (complete response [CR], partial response [PR], or stable disease [SD]) after 12 weeks of study treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease stabilization (CR, PR, or SD) after 6 and 18 weeks of study treatment |  |  | 
| Objective response (CR and PR) to gefitinib treatment after weeks 6, 12, and 18 |  |  | 
| Adverse reactions to gefitinib treatment measured after completion of study treatment |  |  | 
| Time to progression (TTP) with gefitinib treatment after completion of study treatment |  |  | 
| Event-free survival (EFS) with gefitinib treatment after completion of study treatment |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, adenocarcinoma of the lung, large cell lung cancer, squamous cell lung cancer