Gemcitabine, Cisplatin, and Gefitinib in Treating Patients Who Are Undergoing Surgery for Stage III Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: 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. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine and cisplatin together with gefitinib before surgery may shrink the tumor so it can be removed. PURPOSE: This phase II trial is studying how well giving gemcitabine and cisplatin together with gefitinib works in treating patients who are undergoing surgery for stage III non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the therapeutic activity of neoadjuvant induction therapy comprising gemcitabine, cisplatin, and gefitinib in patients with stage IIIA non-small cell lung cancer undergoing surgery. Secondary Determine the safety profile of this regimen in these patients. Determine the stage downsizing and complete resectability rate in patients with no progressive disease who undergo surgery after treatment with this regimen. OUTLINE: This is an open-label, nonrandomized, multicenter study. Patients receive induction therapy comprising gemcitabine IV over 30 minutes on days 1, 8, 22, 29, 43, and 50; cisplatin IV over 3-6 hours on days 2, 23, and 44; and oral gefitinib once daily on days 51-79. Treatment continues in the absence of disease progression or unacceptable toxicity. Within 2-7 days after completion of induction therapy, patients with no progressive disease undergo tumor resection. After completion of study treatment, patients are followed at least every 3 months for 2 years and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

Official Title
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Phase II Study With Gefitinib (Sequentially) Following Gemcitabine/Cisplatin as Induction Regimen for Patients With Stage IIIA N2 NSCLC

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: gefitinib
* Drug: gemcitabine hydrochloride
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed primary non-small cell lung cancer (NSCLC) Clinical stage IIIA by chest CT scan Unresectable N2 disease by mediastinoscopy, mediastinotomy, thoracotomy, or video-assisted thoracic surgery Measurable disease At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan Planning to undergo lobectomy or pneumonectomy after induction therapy No N3 or metastatic disease by physical exam, thoracic CT scan, bone scan, and CT scan or ultrasound of the liver and adrenal glands No pleural or pericardial effusion No superior vena cava syndrome No diffuse interstitial pulmonary fibrosis No signs or symptoms of CNS involvement PATIENT CHARACTERISTICS: Age Over 18 Performance status WHO 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count > 1,500/mm^3 Platelet count > 100,000/mm^3 Hepatic AST and ALT ≤ 1.5 times upper limit of normal (ULN) Bilirubin normal Alkaline phosphatase ≤ 2.5 times ULN Renal Creatinine ≤ 1.25 times ULN Creatinine clearance ≥ 60 mL/min Cardiovascular No medically uncontrolled congestive heart failure or angina pectoris No uncontrolled hypertension or arrhythmia No myocardial infarction within the past year Other Not pregnant or nursing Fertile patients must use effective contraception Physically and mentally fit to receive gemcitabine- and cisplatin-containing chemotherapy Physiologically fit to undergo surgery No uncontrolled, active infection requiring IV antibiotics No history of hypersensitivity to gefitinib or any of its excipients No motor or sensory neurotoxicity ≥ grade 2 No other primary malignancy within the past 5 years except carcinoma in situ of the cervix or adequately treated basal cell skin cancer No prior melanoma, breast cancer, or renal cell cancer No psychological, familial, sociological, or geographical condition that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy Chemotherapy No prior chemotherapy for NSCLC No other concurrent chemotherapy Endocrine therapy No concurrent antiestrogen therapy Concurrent replacement steroids and antiemetic steroids allowed Radiotherapy No prior radiotherapy for NSCLC Surgery See Disease Characteristics No prior surgery for NSCLC Other More than 1 month since prior and no concurrent investigational agents No other prior therapy for NSCLC No concurrent CYP3A4 inducers, including any of the following: Phenytoin Carbamazepine Rifampin Barbiturates (e.g., phenobarbital) Hypericum perforatum (St. John's wort) No concurrent systemic retinoids No other concurrent antitumor therapy

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: gefitinib|nan|
|Drug: gemcitabine hydrochloride|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate as measured by RECIST criteria prior to surgery |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate as measured by RECIST criteria prior to surgery |  |  | 
| Toxicity as assessed by CTC |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIA non-small cell lung cancer