Cisplatin and Docetaxel With or Without Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Newly Diagnosed Stage III Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Cisplatin and docetaxel may make tumor cells more sensitive to radiation therapy. Giving more than one drug (combination chemotherapy) together with radiation therapy before surgery may shrink the tumor so it can be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving cisplatin and docetaxel together with radiation therapy is more effective than giving cisplatin together with docetaxel in treating non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying cisplatin, docetaxel, and radiation therapy to see how well they work compared to cisplatin and docetaxel in treating patients who are undergoing surgery for newly diagnosed stage III non-small cell lung cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Compare overall survival of patients with newly diagnosed favorable prognosis stage IIIA non-small cell lung cancer treated with neoadjuvant cisplatin and docetaxel with vs without thoracic conformal radiotherapy followed by surgical resection and docetaxel. Secondary Compare median and progression-free survival of patients treated with these regimens. Compare clinical and pathologic response rates in patients treated with these regimens. Compare the toxicity of these regimens in these patients. Correlate pathological complete response with disease-free and overall survival of patients treated with these regimens. Correlate DNA damage repair genes (ERCC1 and XRCC1), microtubule-related proteins (TUBB-III and MAP4), and shed tumor DNA with response and outcome in patients treated with these regimens. Correlate protein profiles, using MALDI-TOF proteomic analysis of tumor and serum, with response and prognosis in patients treated with these regimens. Compare quality of life of patients treated with these regimens. Determine the efficacy of fludeoxyglucose F 18 positron emission tomography scanning in assessing pathological response of the tumor and the mediastinal lymph nodes and in predicting long-term outcome in patients treated with these regimens. Correlate comorbid conditions with survival of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to T stage (T1 vs T2-3), number of involved mediastinal lymph nodes (1 vs 2 or more vs not evaluable), and nodal micrometastases vs clinically involved nodes (mN2 vs cN2). Induction therapy: Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive cisplatin IV over 1 hour and docetaxel IV over 1 hour on days 1 and 22. Arm II: Patients undergo thoracic conformal radiotherapy once daily 5 days a week for approximately 5½ weeks (total of 28 doses). Patients also receive cisplatin IV over 1 hour on days 1, 8, 22, and 29 and docetaxel IV over 1 hour on days 1, 8, 15, 22, and 29. Surgery: Within 4-8 weeks after completion of induction therapy, patients with stable disease or better undergo a lobectomy or pneumonectomy with a formal systematic mediastinal lymph node dissection. Consolidation therapy: Beginning 4-6 weeks after surgery, patients receive docetaxel IV over 1 hour on days 1, 22, and 43 and pegfilgrastim or filgrastim (G-CSF) subcutaneously on days 2, 23, and 44. Quality of life is assessed at baseline, within 2 weeks after completion of induction therapy, and then at 6 and 12 months after surgery. After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 574 patients will be accrued for this study within 4 years.

Official Title
-----------------
Phase III Randomized Trial of Preoperative Chemotherapy Versus Preoperative Concurrent Chemotherapy and Thoracic Radiotherapy Followed by Surgical Resection and Consolidation Chemotherapy in Favorable Prognosis Patients With Stage IIIA (N2) Non-Small Cell Lung Cancer

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Biological: filgrastim
* Biological: pegfilgrastim
* Drug: cisplatin
* Drug: docetaxel
* Procedure: adjuvant therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC)*, including any of the following cellular types: Adenocarcinoma Squamous cell carcinoma Large cell carcinoma Non-lobar and non-diffuse bronchoalveolar cell carcinoma NSCLC not otherwise specified NOTE: *Diagnosed within the past 3 months; diagnosis by mediastinal nodal biopsy or needle aspiration allowed provided a distinct lung primary (separate from the nodes) is clearly evident on CT scan Stage IIIA disease T1-T3 disease If pleural effusion is present, must meet ≥ 1 of the following criteria to exclude T4 disease: Pleural effusion cytologically negative by thoracentesis Documented absence of pleural metastases and pleural effusion cytologically negative by thoracoscopy (for patients with pleural effusion on CT scan [but not on chest x-ray] that is deemed too small to tap safely under either CT scan or ultrasound guidance) Confirmed positive ipsilateral mediastinal lymph node(s) (N2 disease)**, with or without positive ipsilateral hilar nodes, by mediastinoscopy, mediastinotomy, endoscopic ultrasound-guided transesophageal biopsy, thoracotomy, video-assisted thoracoscopy, Wang needles, or fine needle aspiration under bronchoscopic or CT guidance N2 nodes must be separate from primary tumor by CT scan or surgical exploration AND maximum diameter ≤ 3.0 cm Mediastinoscopy OR other means of mediastinal lymph node biopsy required (regardless of the primary tumor site) for patients with subcarinal lymphadenopathy by size criteria or by positron emission tomography (PET) scan If the lymph nodes in the contralateral mediastinum and neck are visible by contrast CT scan of the chest AND are ≥ 1.0 cm OR if contralateral involvement is suggested by PET scan, lymph nodes must be confirmed negative by one of the above diagnostic procedures AND N3 status must be confirmed negative by histology or cytology No palpable lymph nodes in the supraclavicular areas or higher in the neck unless proven benign by excisional biopsy A nodal biopsy or needle aspiration may be omitted provided all of the following criteria are true: Paralyzed left true vocal cord by bronchoscopy or indirect laryngoscopy Nodes visible in the aortopulmonary window (level 5) region on CT scan Distinct primary tumor (separate from the nodes) is visible by CT scan No evidence of subcarinal nodal involvement by CT scan NOTE: **PET scan positivity is not sufficient to establish N2 nodal status Measurable disease by chest x-ray and/or contrast-enhanced CT scan Candidate for surgery Resectable disease No distant metastases, including other ipsilateral or contralateral parenchymal lesions or liver or adrenal metastases, by history or physical examination, fludeoxyglucose F 18 PET scan, MRI or CT scan of the brain, chest x-ray and/or CT scan of the lungs and upper abdomen PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,800/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed) Hepatic ALT and AST ≤ 2.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Bilirubin ≤ 1.5 times ULN No hepatic insufficiency resulting in clinical jaundice or coagulation defects Renal Creatinine clearance ≥ 60 mL/min Cardiovascular No unstable angina or congestive heart failure requiring hospitalization within the past 6 months No transmural myocardial infarction within the past 6 months Pulmonary FEV_1 ≥ 2.0 L OR Predicted post-resection FEV_1 ≥ 0.8 L DLCO ≥ 50% of predicted No chronic obstructive pulmonary disease exacerbation No other respiratory illness requiring hospitalization or that would preclude study therapy Immunologic No AIDS No prior allergic reaction to the study drugs No history of severe hypersensitivity to other drugs formulated with polysorbate 80 No acute bacterial or fungal infection requiring IV antibiotics Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No unintentional weight loss > 5% of body weight within the past 6 months No pre-existing peripheral neuropathy ≥ grade 2 No other invasive malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the breast, oral cavity, or cervix No other severe active comorbidity PRIOR CONCURRENT THERAPY: Biologic therapy No prior biological agent for this cancer No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), or pegfilgrastim during study induction therapy (for patients randomized to the chemoradiotherapy arm) Chemotherapy No prior systemic chemotherapy for this cancer Prior chemotherapy for a different cancer allowed Endocrine therapy Not specified Radiotherapy No prior radiotherapy to the region of this cancer that would result in overlap of radiotherapy fields No routine post-operative radiotherapy No concurrent intensity modulated radiotherapy Surgery See Disease Characteristics Other No prior gefitinib for this cancer No concurrent amifostine

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Induction chemotherapy, surgery, consolidation chemotherapy<br>Induction/surgery/consolidation | Biological: filgrastim<br>* Consolidation chemotherapy<br>Biological: pegfilgrastim<br>* Consolidation chemotherapy<br>Drug: cisplatin<br> <br> Drug: docetaxel<br> <br> Procedure: adjuvant therapy<br> <br> Procedure: conventional surgery<br> <br> Procedure: neoadjuvant therapy<br> <br> |
| Other: Chemotherapy and radiation, surgery, consolidation ch<br>Induction/radiation/surgery/cosolidation | Biological: filgrastim<br>* Consolidation chemotherapy<br>Biological: pegfilgrastim<br>* Consolidation chemotherapy<br>Drug: cisplatin<br> <br> Drug: docetaxel<br> <br> Procedure: adjuvant therapy<br> <br> Procedure: conventional surgery<br> <br> Procedure: neoadjuvant therapy<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Overall Survival |  | Date of death or date of last follow-up | 

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