Paclitaxel and Carboplatin With or Without Nitroglycerin in Treating Patients With Previously Untreated Stage III or Stage IV Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Nitroglycerin may help carboplatin and paclitaxel work better by making tumor cells more sensitive to the drugs. PURPOSE: This phase II randomized trial is studying how well giving nitroglycerin together with paclitaxel and carboplatin works and compares it to giving paclitaxel and carboplatin alone in treating patients with previously untreated stage III or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: To evaluate tumor response rate and safety of nitroglycerin as a potentiator of anticancer combination therapy comprising paclitaxel and carboplatin in patients with previously untreated stage IIIB or IV non-small cell lung cancer. OUTLINE: This is a multicenter, randomized, controlled study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive nitroglycerin, paclitaxel, and carboplatin. Arm II: Patients receive paclitaxel and carboplatin. In both arms, treatment continues for 6 courses in the absence of disease progression or unacceptable toxicity.

Official Title
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A Phase II, Multinational and Multicenter, Randomized, Controlled Study of Paclitaxel and Carboplatin With vs Without Nitroglycerin in Patients With Untreated Advanced Non-small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: nitroglycerin
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer Stage IIIB or IV disease that cannot be treated by radical irradiation Tumor lesions must be objectively evaluated according to WHO criteria (maximum diameter is no shorter than twice the slice width and no shorter than 10 mm) by CT scan No brain metastasis PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy ≥ 3 months Neutrophil count > 2,000/μL Hemoglobin > 10.0 g/dL Platelet count > 100,000/μL Serum bilirubin < 2.0 mg/dL ALT and AST < 100 IU/L Serum creatinine < 2.0 mg/dL PaO_2 ≥ 70 mm Hg No cardiac problems, including any of the following: Poorly controlled hypertension Unstable angina Congestive heart failure Myocardial infarction within the past year Ventricular arrhythmia that requires treatment except single, well-controlled isolated ventricular extrasystole No chronic active hepatitis or cirrhosis requiring treatment except hepatitis virus carriers who do not need treatment No comorbidity of interstitial pneumonia and pulmonary fibrosis requiring treatment No other cancer requiring treatment except a malignant tumor curatively resected with no recurrence No severe psychiatric disorders including schizophrenia or dementia Cardiothoracic ratio < 60% by chest x-ray No history of severe drug allergy or allergy to polyoxyethylene castor oil (in some anesthetic drugs or muscle relaxants) or polysorbate 80 Patients in whom nitroglycerin preparations are contraindicated are not eligible, including any of the following: Severe hypotension (e.g., systolic blood pressure ≤ 80 mm Hg) Angle-closure glaucoma History of hypersensitivity to nitrate/nitrite ester drugs Not pregnant or nursing PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy Pleurodesis is not considered chemotherapy At least 1 week since prior and no other concurrent nitric oxide donors (e.g., nitroglycerin) At least 1 week since prior and no concurrent calcium antagonists At least 1 week since prior and no concurrent drugs for erectile dysfunction that inhibit phosphodiesterase 5 (e.g., sildenafil citrate or vardenafil hydrochloride hydrate) More than 24 hours since prior and no concurrent administration of the following: Antifungal azoles, including ketoconazole, miconazole, or itraconazole Macrolides, including erythromycin or clarithromycin Cyclosporines Benzodiazepines, including diazepam, triazolam, or midazolam Vitamin A Steroid hormones, including ethinylestradiol No concurrent participation in another clinical trial

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carboplatin|nan|
|Drug: nitroglycerin|nan|
|Drug: paclitaxel|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response rate |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  |  | 
| Adverse event and its severity |  |  | 
| Overall survival |  |  | 
| Change in the plasma concentration of VEGF between before and after the three-day administration of nitroglycerin prior to the start of the administration of anticancer drugs in the first course of the treatment |  |  | 
| Change in the number of endothelial progenitor cells in blood between before and after the three-day administration of nitroglycerin prior to the start of the administration of anticancer drugs in the first course of the treatment |  |  | 
| Blood concentration of paclitaxel and carboplatin immediately and two hours after the administration of the anticancer drug (paclitaxel) in the first course of treatment |  |  | 

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