Polyglutamate Paclitaxel Compared With Gemcitabine or Vinorelbine in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known whether polyglutamate paclitaxel is more effective than gemcitabine or vinorelbine in treating non-small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of polyglutamate paclitaxel with that of gemcitabine or vinorelbine in treating patients who have stage IIIB, stage IV, or recurrent non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Compare the efficacy of polyglutamate paclitaxel (CT-2103) vs gemcitabine or vinorelbine, in terms of duration of overall survival, in patients with stage IIIB or IV or recurrent non-small cell lung cancer who have a performance status of 2. Compare the safety of these regimens in these patients. Compare the disease control (percentage of patients with no disease progression for at least 12 weeks) and time to progression in patients treated with these regimens. Compare the response rate in patients with measurable disease treated with these regimens. Compare the improvement in lung cancer symptoms in patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to gender, disease stage (IV vs other), geographic location (US vs Western Europe and Canada vs the rest of the world), and prior brain metastases (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive polyglutamate paclitaxel (CT-2103) IV over 10 minutes on day 1 every 21 days. Arm II: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 every 28 days OR vinorelbine IV over 6-10 minutes on days 1, 8, and 15 every 21 days. Treatment repeats in both arms for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed at 3 weeks and then every 8 weeks thereafter. PROJECTED ACCRUAL: A total of 370 patients (185 per treatment arm) will be accrued for this study within 13 months.

Official Title
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CT-2103 vs Gemcitabine or Vinorelbine for the Treatment of PS = 2 Patients With Chemotherapy Naive Advanced Non-Small Cell Lung Cancer (NSCLC): A Phase III Study

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: paclitaxel poliglumex
* Drug: vinorelbine tartrate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) meeting 1 of the following criteria: Locally advanced or recurrent disease previously treated with radiotherapy and/or surgery Stage IIIB and not a candidate for combined modality therapy Stage IV No evidence of small cell carcinoma, carcinoid, or mixed small cell/non-small cell histology Cytological diagnosis must be based on the following: No cellular diagnosis by sputum cytology alone Cytologic specimens obtained from brushings, washings, or needle aspiration of a defined lesion or pleural effusion are acceptable Measurable or nonmeasurable disease Brain metastases allowed provided patient received prior standard antitumor therapy for CNS metastases (e.g., whole brain radiotherapy, stereotactic radioablation, or surgery) and the following conditions are met: Neurologic function stable for at least 2 weeks before study entry Off steroid therapy or on a tapering regimen Recovered from prior therapy PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 2 Life expectancy Not specified Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than upper limit of normal (ULN) SGOT/SGPT no greater than 2.5 times ULN (5 times ULN if liver metastases present) Alkaline phosphatase no greater than 2.5 times ULN (except for laboratory documentation that demonstrates bone origin) Renal Creatinine no greater than 1.5 times ULN Cardiovascular No unstable angina No myocardial infarction within the past 6 months Cardiac conduction abnormalities (e.g., bundle branch block or heart block) allowed provided cardiac status has been stable for at least 6 months prior to study entry Neurologic See Disease Characteristics No neuropathy greater than grade 1 No evidence of unstable neurologic symptoms within the past 4 weeks (2 weeks for neurologic symptoms due to brain metastases) Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No intolerance to excipients of polyglutamate paclitaxel (e.g., poly-L-glutamic acid, poloxamer 188, dibasic sodium phosphate, or monobasic sodium hydroxide) No clinically significant active infection No other concurrent primary malignancy except carcinoma in situ or nonmelanoma skin cancer No other unstable medical conditions No circumstance that would preclude study completion or follow-up PRIOR CONCURRENT THERAPY: Biologic therapy No prior systemic biologic agent for lung cancer Chemotherapy See Disease Characteristics No prior systemic chemotherapy for lung cancer including radiosensitizing agents Endocrine therapy See Disease Characteristics Radiotherapy See Disease Characteristics No concurrent radiotherapy Surgery See Disease Characteristics Recovered from prior major surgery Other More than 12 weeks since prior participation in any research study or treatment with investigational drugs Recovered from prior investigational therapy or stable for 4 weeks before study treatment No other concurrent investigational drugs No other concurrent systemic antitumor therapy No concurrent amifostine Concurrent bisphosphonates allowed

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: gemcitabine hydrochloride|nan|
|Drug: paclitaxel poliglumex|nan|
|Drug: vinorelbine tartrate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 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