S9900: Surgery With or Without Combination Chemotherapy in Treating Patients With 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 if surgery plus combination chemotherapy is more effective than surgery alone for non-small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without combination chemotherapy in treating patients who have non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Compare survival of patients with previously untreated stage IB, II, or selected IIIA non-small cell lung cancer after preoperative chemotherapy comprising paclitaxel and carboplatin plus surgery vs surgery alone. Compare these regimens in terms of operative mortality and other toxic effects in these patients. Evaluate the response rates (confirmed and unconfirmed) and toxic effects associated with combined paclitaxel and carboplatin in these patients. Obtain samples for correlation of radiologic, pathologic, molecular, and biologic factors with the outcome in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to clinical stage (IB or IIA vs IIB or IIIA). Patients are randomized to one of two treatment arms: Arm I: Patients undergo thoracotomy. All accessible hilar (level 10) lymph nodes are dissected, and complete mediastinal lymph node sampling is performed. Arm II: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for a maximum of 3 courses in the absence of disease progression or unacceptable toxicity. Within 2-6 weeks of course 3, patients undergo thoracotomy and lymph node dissection as in arm I. Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually until year 10. PROJECTED ACCRUAL: A total of 600 patients (300 per treatment arm) will be accrued for this study within 4 years.

Official Title
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A Randomized Phase III Trial of Surgery Alone or Surgery Plus Preoperative Paclitaxel/Carboplatin in Clinical Stage IB (T2N0), II (T1-2N1, T3N0) and Selected IIIA (T3N1) Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: paclitaxel
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically proven non-small cell lung cancer (NSCLC), meeting 1 of the following staging criteria: Stage IB (T2, N0) Stage II T1-2, N1 with negative mediastinoscopy OR T3, N0 Selected stage IIIA with negative mediastinoscopies T3, N1, excluding superior sulcus Positive level 10 hilar nodes allowed if mediastinoscopy negative Apical tumors with no clinical symptoms allowed No symptomatic tumors (T3, N0 or T3, N1) involving the superior sulcus No Pancoast's tumors Negative mediastinoscopy required in all patients with clinically positive mediastinal or hilar lymph nodes to ensure no N2 disease Bidimensionally measurable or evaluable disease by chest x-ray or contrast-enhanced CT scan T3, N0 disease assessable only by bronchoscopy must be affirmed by 2 observers and documented by photograph that includes main carina PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0 or 1 Life expectancy: Not specified Hematopoietic: Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 WBC at least 4,000/mm^3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT or SGPT no greater than 2 times ULN Alkaline phosphatase no greater than 2 times ULN Renal: Creatinine no greater than 1.5 times ULN Creatinine clearance at least 50 mL/min Pulmonary: See Disease Characteristics Preresection FEV_1 greater than 2.0 L OR Predicted postresection FEV_1 greater than 1.0 L No postobstructive pneumonia Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No serious infection No other serious medical condition that would preclude study compliance No prior allergic reactions to drugs containing Cremophor No prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior systemic chemotherapy for NSCLC No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior systemic radiotherapy for NSCLC No concurrent radiotherapy Surgery: At least 5 years since prior resection of lung disease Other: No other concurrent investigational therapy No other concurrent anticancer 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: preooperative chemo followed by surgery<br>carboplatin paclitaxel conventional surgery | Drug: carboplatin<br> <br> Drug: paclitaxel<br> <br> Procedure: conventional surgery<br> <br> |
| Active Comparator: Surgery alone<br>conventional surgery | Procedure: conventional surgery<br> <br> |

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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stage I non-small cell lung cancer, stage II non-small cell lung cancer, stage IIIA non-small cell lung cancer