Chemotherapy and Radiation Therapy With or Without Panitumumab in Treating Patients With Stage IIIA Non-Small Cell Lung Cancer
Chemotherapy and Radiation Therapy With or Without Panitumumab in Treating Patients With Stage IIIA Non-Small Cell Lung Cancer
RATIONALE: Drugs used in chemotherapy (CT), such as paclitaxel and carboplatin, work in
 different ways to stop the growth of tumor cells, either by killing the cells or by stopping
 them from dividing. Radiation therapy (RT) uses high-energy x-rays to kill tumor cells.
 Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some
 block the ability of tumor cells to grow and spread. Others find tumor cells and help kill
 them or carry tumor-killing substances to them. Giving these treatments before surgery may
 make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is
 not yet known whether chemotherapy and radiation therapy are more effective when given with
 or without panitumumab in treating patients with non-small cell lung cancer.

 PURPOSE: This randomized phase II trial is studying chemotherapy and radiation therapy to see
 how well they work when given 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