Carboplatin With Either Paclitaxel Poliglumex or Paclitaxel in Treating Women With Stage IIIB, Stage IV, or Recurrent 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, paclitaxel, and paclitaxel poliglumex, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving carboplatin together with paclitaxel poliglumex is more effective than giving carboplatin together with paclitaxel in treating non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying carboplatin and paclitaxel poliglumex to see how well they work compared with carboplatin and paclitaxel in treating women with stage III, stage IV, or recurrent non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Compare the overall survival of patients with chemotherapy-naïve stage IIIB or IV or recurrent non-small cell lung cancer treated with paclitaxel poliglumex and carboplatin vs paclitaxel and carboplatin. Secondary Compare the progression-free survival of women treated with these regimens. Compare the disease control in women treated with these regimens. Compare the clinical benefit in women treated with these regimens. Compare the response rate in women treated with these regimens. Compare the quality of life of women treated with these regimens. Compare the safety and tolerability in women treated with these regimens. OUTLINE: This is a multicenter study. Patients are stratified according to age (≥ 60 vs < 60 years old), geographical location (United States of America, Canada, or Australia vs the rest of the world), extent of disease (independent of brain metastases, i.e., brain metastases are not considered in determining extent of disease) (intrathoracic disease only vs extrathoracic disease), and ECOG performance status (0 or 1 vs 2). Patients will be randomized to 1 of 2 treatment arms. Arm I: Patients receive paclitaxel poliglumex IV over 10 minutes followed by carboplatin IV over 30 minutes on day 1. Arm II: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, before each course, and at the completion of study treatment by the Pain Assessment Patient Questionnaire, the Pulmonary Symptom Index, and the Functional Assessment of Cancer Therapy- Lung Cancer Subscale (FACT-LCS) (only in countries in which a validated translation is currently available). After completion of study therapy, patients are followed at least monthly.

Official Title
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Paclitaxel Poliglumex (CT-2103)/Carboplatin vs Paclitaxel/Carboplatin for the Treatment of Chemotherapy-Naïve Advanced Non-Small Cell Lung Cancer (NSCLC) in Women With Estradiol >30 pg/mL

Conditions
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Lung Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) Cytologic specimens obtained by brushings, washings, or needle aspiration of a defined lesion or from a pleural effusion are acceptable; sputum cytology alone is not acceptable for determining cell type Must meet one of the following criteria: Recurrent disease following completion of radiation or surgery Stage IIIB disease and not a candidate for combined modality therapy (primary radiation therapy or surgery) Stage IV disease Patients may have either measurable or nonmeasurable disease according to RECIST criteria Baseline estradiol > 30 pg/mL Patients on hormone replacement therapy are eligible provided baseline estradiol > 30 pg/mL Patients with known brain metastases must have received standard antitumor treatment (e.g. whole brain radiation, stereotactic radioablation, or surgery) for their CNS metastases as defined by the site's institutional standards Neurologic function must have been stable for 2 weeks before randomization and patients must either be off steroid therapy for their brain metastases or on a tapering regimen Patients must have recovered from therapy for their brain metastases with no evidence of significant unstable neurological symptoms within the 4 weeks before study randomization No evidence of small cell carcinoma, carcinoid, or mixed small cell/non-small cell histology PATIENT CHARACTERISTICS: Female ECOG performance score 0-2 Life expectancy ≥ 12 weeks Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 10 g/dL (may be achieved with transfusion) Creatinine ≤ 1.5 times upper limit of normal (ULN) Total bilirubin ≤ 1.5 times ULN (CTC grade 1) (patients with Gilbert syndrome or other hereditary bilirubin defects may be included regardless of bilirubin levels) SGOT and SGPT ≤ 2.5 times ULN (CTC grade 0 or 1) (5 times ULN [CTC grade 0 to 2] if due to liver metastases) Alkaline phosphatase ≤ 2.5 times ULN except for elevated alkaline phosphatase with laboratory documentation that demonstrates bone origin No pregnant women or nursing mothers Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after study participation No known hypersensitivity to study drugs or excipients Meets all of the following criteria: No weight loss > 10% in previous 6 months Lactate dehydrogenase (LDH) ≤ 600 IU/L (central laboratory) regardless of weight loss LDH ≤ 400 IU/L (central laboratory) and no weight loss ≥ 5% in previous 6 months BMI ≤ 35 No concurrent primary malignancies except for carcinoma in situ or non-melanoma skin cancer No neuropathy grade 2 or greater No clinically significant active infection for which active therapy is underway No unstable medical conditions including unstable angina or myocardial infarction within the past 6 months Patients with evidence of cardiac conduction abnormalities are eligible if their cardiac status is stable No circumstance that would preclude completion of the study or the required follow-up PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from major surgery At least 7 days since prior local palliative radiotherapy At least 30 days since prior radiation therapy with curative intent At least 4 weeks since prior investigational therapy, unless local requirements are more stringent No prior systemic chemotherapy for the treatment of lung cancer, including systemic radiosensitizers used to treat brain metastases or any biologic agents No concurrent non-protocol-specified systemic antitumor therapy No concurrent amifostine, investigational agents, other cytotoxic agents for this disease No concurrent radiotherapy (with the exception of radiotherapy for brain or bone metastases for palliative purposes or radiotherapy for a condition other than NSCLC that was ongoing at the time of randomization) Patients receiving palliative radiotherapy (treatment for symptomatic metastatic disease) may be treated while on study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive paclitaxel poliglumex IV over 10 minutes followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | Drug: carboplatin<br>* Given IV<br>Drug: paclitaxel poliglumex<br>* Given IV<br>|
| Active Comparator: Arm II<br>Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | Drug: carboplatin<br>* Given IV<br>Drug: paclitaxel<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  |  | 
| Disease control |  |  | 
| Clinical benefit as defined by use of opiates, growth factors, and transfusions, |  |  | 
| Response rate as assessed by complete response or partial response per RECIST criteria |  |  | 
| Quality of life as assessed by Fact-LCS Scores and Pulmonary Symptom Index (PSI) Scores and Pain Scores |  |  | 
| Safety as assessed by NCI CTCAE Version 3 |  |  | 

 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