Randomized Phase II Study of Pre-operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy +/- Cetuximab in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer (Cetuximab Closed as of 05/14/10)

Inclusion Criteria

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 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

- Pleural effusion allowed provided one of the following criteria is met:

- If pleural fluid is present either before or after pre-study mediastinoscopy or
exploratory thoracotomy, a thoracentesis must be performed to document that the
pleural effusion is cytologically negative

- If pleural fluid is present on CT scan, but is deemed too small to tap safely
under either CT scan or ultrasound guidance, a thoracoscopy should be done, if
feasible, to document the absence of pleural metastases and to document that the
pleural effusion is cytologically negative

- 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 or nursing

- 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:

- Uncontrolled cardiac disease (e.g., uncontrolled hypertension, unstable angina,
myocardial infarction within the past 6 months, uncontrolled congestive heart
failure, or cardiomyopathy [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