Phase II Trial of Combined Modality Therapy With Growth Factor Support in Locally Advanced NSCLC

Inclusion Criteria:

- Histologically or cytologically confirmed NSCLC: Either histologic or cytologic
proof of a newly diagnosed non-small cell lung cancer is required. A biopsy with
histology is preferred, but cytology is allowed. Histology or cytology from involved
mediastinal or supraclavicular lymph nodes alone will be allowed if a separate distal
primary lesion is clearly evident on radiographs (i.e., a second biopsy will not be
required).

- Patients with two or more parenchymal lesions on same or opposite sides of the lung
are ineligible.

- Must have unresectable Stage IIIA (N2) or IIIB disease and also satisfy the following
criteria:

- Unresectable Stage IIIA (N2) patients:

- N2 mediastinal lymph nodes must be multiple and/or bulky on CT scan or X-ray,
such that, in the opinion of the treating investigator, the patient is not a
candidate for induction chemotherapy or chemoradiotherapy followed by surgical
resection.

- N2 status must be documented by any one of the following methods:

- Histologic or cytologic proof of N2 disease by exploratory thoracotomy,
thoracoscopy, mediastinoscopy, mediastinotomy, Wang needle biopsy, fine needle
aspiration under bronchoscopic or CT guidance or other method

- Node positivity by PET scan

- Nodes >2 cm on CT scan

- Paralyzed left true vocal cord with separate left lung primary distinct from AP
window nodes on CT Scan

- Stage IIIB patients:

- Pathologic documented or radiographically documented positive N3 nodes.

- Patients with positive supraclavicular or scalene lymph nodes must not have disease
extending up into the cervical region evidenced by one of the following:

- Fine needle aspiration, core needle biopsy or excisional biopsy of
supraclavicular N3 nodes

- Biopsy of contralateral mediastinal N3 nodes by mediastinoscopy, mediastinotomy,
or thoracotomy

- Fine needle aspiration, core needle or Wang needle biopsy under CT or
bronchoscopic fluoroscopic guidance of enlarged contralateral N3 mediastinal
nodes

- Contralateral mediastinal nodes >2 cm on CT scan

- Contralateral node positivity on PET scan

- Right sided primary with paralyzed left true vocal cord

- Any of the following T4 lesions: Tumor of any size that invades any of the following:
mediastinum, heart, great vessels, trachea, esophagus, vertebral body or carina:

- Written documentation of type of T4 extent by attending surgeon if the patient
has had an exploratory thoracotomy or thoracoscopy

- T4 involvement of the trachea or carina by direct bronchoscopic visualization

- T4 involvement of the heart, esophagus, aorta, or vertebral body documented by
CT scan, MRI or transesophageal ultrasound

- T4 involvement of the mediastinum may also be accepted by CT or MRI criteria if,
in absence of the above organ involvement, there is a soft tissue extension
directly into the mediastinal space.

- Radiographic criteria for involvement of main pulmonary artery or vein is allowed
only if there is a mediastinal soft tissue mass.

- Age > 18 years

- ECOG performance status 0 or 1

- Ability to give informed consent

- Adequate organ and marrow function as evidenced by the following peripheral blood
counts or serum chemistries at study entry:

- WBC > 4,000/µL

- Absolute neutrophil count > 1,500/mm3

- Platelet count > 100 x 103 cells/mm3

- Bilirubin < 1.5 x institutional ULN

- AST or ALT < 2.5 x institutional ULN

- Alkaline Phosphatase <2.5 x institutional ULN

- Serum Creatinine < 2.0mg/dL and/or adequate creatinine clearance

- Adequate pulmonary function (FEV>1.5 liters, or if <1.5 liters, the predicted FEV1of
the contralateral lung must be >800 cc based on the quantitative split function
testing. (Predicted FEV1= FEV1 x % perfusion to uninvolved lung from quantitative
lung V/Q scan report)

- Must have one measurable lesion by chest X-ray or CT scan. Lesion(s) must be
accurately measured in at least one dimension (longest diameter to be recorded) as
>20mm with conventional techniques or as >10mm with spiral CT scan

- Men and women of childbearing potential must agree to use effective contraception
while on treatment and for 6 months after treatment

Exclusion Criteria:

- Malignant pleural or pericardial effusion

- Prior chemotherapy or radiation therapy

- Pregnant or lactating females

- Primary malignancy other than basal or squamous carcinoma of the skin or carcinoma in
situ of the cervix, or any other cancer for which the patient has been disease free
for five years. Other in situ malignancies (e.g. breast, bladder, etc) in the past 3
years are permissible

- Unintentional weight loss >10% body weight within the last 3 months

- Unable to provide informed consent

- Any pre-malignant myeloid condition or any malignancy with myeloid characteristics

- Active infection

- Known hypersensitivity to E. coli-derived proteins, pegfilgrastim, Filgrastim, or any
other component of the product

- Significant nonmalignant disease including: documented HIV infection; uncontrolled
heart disease, and poorly controlled diabetes

- Treatment within the last 30 days with any experimental agent