Carboplatin and Gemcitabine Combined With Celecoxib and/or Zileuton in Treating Patients With Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as carboplatin and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib and zileuton may stop the growth of tumor cells by stopping blood flow to the tumor and may block the enzymes necessary for tumor cell growth. Combining chemotherapy with celecoxib and/or zileuton may kill more tumor cells. PURPOSE: Randomized phase II trial to study the effectiveness of combining celecoxib and/or zileuton with carboplatin and gemcitabine in treating patients who have advanced non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Compare the efficacy of carboplatin and gemcitabine with celecoxib and/or zileuton, in terms of 7-month progression-free survival, in patients with advanced non-small cell lung cancer. Secondary Compare the response rate, distribution of survival, and failure-free survival time of patients treated with these regimens. Correlate CYFRA and serum vascular endothelial growth factor levels with response and survival of patients treated with these regimens. Correlate cyclo-oxygenase-2 and 5-lipoxygenase expression with survival of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive gemcitabine IV over 30 minutes on days 1 and 8, carboplatin IV over 30 minutes on day 1, and oral zileuton 4 times daily on days 1-21. Arm II: Patients receive gemcitabine and carboplatin as in arm I and oral celecoxib twice daily on days 1-21. Arm III: Patients receive gemcitabine and carboplatin as in arm I, oral celecoxib as in arm II, and oral zileuton as in arm I. In all arms, treatment repeats every 21 days for 6 courses. Patients with responding or stable disease continue courses of zileuton and/or celecoxib in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for 1 year, every 2 months for 2 years, and then every 4 months for 3 years or until disease progression. PROJECTED ACCRUAL: A total of 117 patients (39 per treatment arm) will be accrued for this study within 11-12 months.

Official Title
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Randomized Phase II Study of Eicosanoid Pathway Modulators and Cytotoxic Chemotherapy in Advanced Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: celecoxib
* Drug: gemcitabine hydrochloride
* Drug: zileuton


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) of 1 of the following cellular types: Adenocarcinoma Large cell Squamous cell Mixed Meets 1 of the following staging criteria: Stage IIIB disease with malignant pleural effusion, supraclavicular node involvement, or contralateral hilar nodes Stage IIIB patients eligible for Cancer and Leukemia Group B protocols of combined chemotherapy and chest irradiation are not allowed Stage IV disease Measurable or nonmeasurable disease Unidimensionally measurable lesions at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan The following are considered nonmeasurable disease: Bone lesions Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Small lesions No leptomeningeal disease Symptomatic CNS metastases must be treated (e.g., surgery, radiotherapy, or gamma knife), neurologically stable, and off steroids PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 1.5 mg/dL AST no greater than 2.0 times upper limit of normal Renal Creatinine no greater than 1.5 mg/dL Cardiovascular None of the following within the past 6 months: Myocardial infarction Unstable angina Symptomatic congestive heart failure Serious uncontrolled cardiac arrhythmia Cerebrovascular accident Transient ischemic attack Symptomatic carotid artery or peripheral vascular disease Deep vein thrombosis Significant thromboembolic event Pulmonary No pulmonary embolism within the past 6 months Gastrointestinal No history of gastrointestinal (GI) bleeding No history of peptic ulcer disease No active GI bleeding Other Not pregnant or nursing No known hypersensitivity to aspirin, NSAIDs, or sulfonamides No currently active second malignancy other than nonmelanoma skin cancer Patients are not considered to have a currently active malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse PRIOR CONCURRENT THERAPY: Biologic therapy No prior immunotherapy for NSCLC Chemotherapy No prior chemotherapy for NSCLC No other concurrent chemotherapy Endocrine therapy See Disease Characteristics No concurrent chronic oral steroids Concurrent episodic steroids for antiemetic purposes allowed No concurrent hormonal therapy Concurrent inhaled steroids allowed when medically indicated Concurrent megestrol for appetite stimulation is allowed Radiotherapy See Disease Characteristics At least 2 weeks since prior radiotherapy and recovered Surgery See Disease Characteristics At least 2 weeks since prior surgery and recovered Other No prior systemic treatments for NSCLC No other concurrent investigational therapy At least 1 week since prior nonsteroidal anti-inflammatory drugs (NSAIDs), including any of the following: Rofecoxib Choline magnesium trisalicylate Ibuprofen Naproxen Etodolac Oxaprozin Diflunisal Nabumetone Tolmetin Valdecoxib No concurrent NSAIDs No concurrent chronic aspirin Concurrent aspirin no greater than 325 mg/day is allowed No concurrent fluconazole No concurrent leukotriene antagonists (e.g., zafirlukast, montelukast, or pranlukast)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gem + Carboplatin + Zileuton<br> | Drug: carboplatin<br>* given IV<br>Drug: gemcitabine hydrochloride<br>* given IV<br>Drug: zileuton<br>* given PO<br>|
| Experimental: Gem + Carboplatin + celecoxib<br> | Drug: carboplatin<br>* given IV<br>Drug: celecoxib<br>* given PO<br>Drug: gemcitabine hydrochloride<br>* given IV<br>|
| Experimental: Gem + carboplatin + zilueton + celecoxib<br> | Drug: carboplatin<br>* given IV<br>Drug: celecoxib<br>* given PO<br>Drug: gemcitabine hydrochloride<br>* given IV<br>Drug: zileuton<br>* given PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival |  | 9 months | 

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