Chemotherapy and Radiation Therapy With or Without Panitumumab in Treating Patients With Stage IIIA Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

• Determine the mediastinal nodal clearance after completion of induction chemoradiotherapy with or without panitumumab in patients with stage IIIA non-small cell lung cancer.

Secondary

• Assess overall survival of these patients.
• Evaluate patterns of first failure in these patients.
• Determine the acute and late adverse events associated with these regimens.
• Assess surgical morbidities in patients with resectable disease at reassessment.
• Determine the correlation between pre- and post-treatment biomarkers (including epidermal growth factor receptor (EGFR) and ras mutation status) and outcomes (mediastinal nodal clearance and overall survival).
• Evaluate the prognostic value of plasma osteopontin and microRNA for overall survival.
• Assess the ability of FDG-PET/CT scan re-staging to predict outcome.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive induction therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo intensity-modulated radiotherapy (IMRT) or 3-dimensional conformal radiotherapy (3D-CRT) once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Beginning approximately 6-12 weeks later, patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21.
• Arm II: Patients receive induction therapy comprising panitumumab IV over 1 hour on days 1, 8, 15, 22, 29, and 36 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 8, 15, 22, 29, and 36. Patients also undergo IMRT or 3D-CRT once daily on days 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47. Beginning approximately 6-12 weeks later, patients receive consolidation therapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1 and 21.
• In both arms, patients with resectable disease and no disease progression may proceed to surgery (thoracotomy, lobectomy, or pneumonectomy) approximately 4-6 weeks after completion of induction therapy. After surgery, patients proceed to consolidation therapy.

After completion of study treatment, patients are followed up at 6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

DISEASE CHARACTERISTICS:

• Histologically confirmed* non-small cell lung cancer (NSCLC), including any of the following histologies:

• Adenocarcinoma
• Adenosquamous
• Large cell carcinoma
• Squamous cell carcinoma
• Non-lobar and non-diffuse bronchoalveolar cell carcinoma
• NSCLC not otherwise specified NOTE: *Documentation of NSCLC may originate from the mediastinal node biopsy or aspiration
• Stage IIIA (T1-T3) disease with a single primary lung parenchymal lesion AND positive ipsilateral mediastinal node or nodes (N2) with or without positive ipsilateral hilar nodes (N1)

• N2 nodes must be separate from primary tumor by either CT scan or surgical exploration
• Maximum nodal diameter of involved N2 nodes cannot exceed 3.0 cm
• N2 status must be pathologically confirmed to be positive by one of the following methods*:

• Mediastinoscopy
• Mediastinotomy (Chamberlain procedure)
• Transesophageal needle biopsy using endoscopic ultrasound (EUS-TBNA)
• Endobronchial ultrasound biopsy using endoscopic ultrasound guidance (EBUS-TBNA)
• Thoracotomy
• Video-assisted thoracoscopy
• Transbronchial needle biopsy by Wang technique (TBNA)
• Fine-needle aspiration under CT guidance NOTE: *PET positivity in the ipsilateral mediastinal lymph nodes is not sufficient to establish N2 nodal status
• Ipsilateral mediastinal nodes associated with right-sided tumor must be biopsied unless all of the following are true:

• Tumor is left sided
• Paralyzed left true vocal cord documented by bronchoscopy or indirect laryngoscopy
• Nodes visible in the anterior/posterior (level 5) region on CT scan
• Distinct primary tumor separate from nodes visible on CT scan
• Histologic (biopsy) or cytologic (needle aspiration or sputum) proof of non-small cell histology from the primary tumor
• If lymph nodes in the contralateral mediastinum and neck are visible on contrast CT scan of the chest and are > 1.0 cm in short axis or if contralateral involvement is suggested by PET scan, then the nodes must be confirmed to be negative
• Measurable disease as determined by contrast-enhanced CT scan

• Primary lung tumor distinct from mediastinal lymph nodes
• If a pleural effusion is present, the following criteria must be met to exclude malignant involvement (incurable M1a disease):

• When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative.
• Exudative pleural effusions are excluded, regardless of cytology;
• Effusions that are minimal (i.e. not visible under ultrasound guidance) that are too small to safely tap are eligible.
• No palpable lymph nodes in the supraclavicular areas or higher in the neck, unless proven to be benign by fine-needle aspiration or biopsy
• No distant metastases

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• Absolute neutrophil count (ANC) ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10.0 g/dL (transfusion allowed)
• Creatinine clearance ≥ 60 mL/min
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Serum albumin > 3.0 g/dL
• Serum magnesium normal (supplementation allowed)
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of treatment
• Forced expiratory volume at one second (FEV1) ≥ 2.0 L OR predicted post-resection FEV1 ≥ 0.8 L
• Diffusion capacity ≥ 50% predicted
• 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 severe, active co-morbidity, including any of the following:

• Current uncontrolled cardiac disease (e.g., uncontrolled hypertension, unstable angina, myocardial infarction within the past 6 months, uncontrolled congestive heart failure, or cardiomyopathy with decreased ejection fraction (<50%)
• Acute bacterial or fungal infection requiring IV antibiotics
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or that would preclude study therapy within the past 4 weeks
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• AIDS or known HIV positivity
• No unintentional weight loss ≥ 5% of body weight within the past 6 months
• No prior severe infusion reaction to a monoclonal antibody
• No pre-existing peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

• No prior systemic chemotherapy or biological therapy (including erlotinib hydrochloride or similar agents) for the study cancer

• Prior chemotherapy for a different cancer allowed
• No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
• No prior therapy that specifically and directly targets the EGFR pathway