Safety of LEAD Radiotherapy Plus Chemoradiation in Patients With Bulky Stage III Non-Small Cell Lung Cancer

Paarticipants will receive a single fraction of LEAD radiation on day 1, followed one day
later by conventionally fractionated concurrent chemoradiation consisting of 60 Gy of
radiation delivered to involved sites of disease and a platinum doublet.

The investigational radiation treatment, a single fraction of LEAD radiation, is to be
followed by conventionally fractionated radiation delivered concurrently with a standard
chemotherapy regimen for stage III non-small cell lung cancer. The following day, patients
will begin concurrent chemotherapy and radiation. Chemotherapy will be delivered under the
management of the treating medical oncologist. Chemotherapy must be a platinum doublet.
Carboplatin and cisplatin are both considered acceptable platinum agents. The use of
cisplatin over carboplatin is strongly encouraged, unless the patient has a contraindication
to cisplatin. The second agent will be at the discretion of the treating medical oncologist;
in the current era, chemotherapy agents are tailored to each patient based on tumor
histology, as well as comorbidities that dictate the tolerance of certain chemotherapeutic
agents. Chemotherapy will be delivered concurrently throughout radiation therapy, beginning
on day 2 of the treatment protocol and on the same day as the start of standard-dose
radiation. Weekly regimens or regimens delivered every 3 weeks are acceptable. Additional
cycles of consolidation chemotherapy are encouraged and will be given at the discretion of
the treating medical oncologist.

Inclusion Criteria:

1. Patients must have histologically or cytologically documented stage III non-small cell
lung cancer including squamous cell, adenocarcinoma, large cell carcinoma and poorly
differentiated non-small cell lung cancer.

2. Patients must have a minimum of 4 cm of measurable disease in any one continuous
dimension as seen on diagnostic CT scan.

3. Pulmonary function tests with forced expiratory volume in 1 second (FEV1) ≥1.45
liters/second.

4. Patients must be 21 years of age or older. There is no maximum age restriction.

5. Patients must have a Zubrod performance status of 0 or 1.

6. Patients must have normal organ and marrow function as defined below:

- leukocyte > 3,000/:I

- absolute neutrophil count >1,500/:I

- platelets >100,000/:I

- bilirubin within normal institutional limits

- Aspartate transaminase (AST/SGOT)/Alanine transaminase (ALT/SGPT) 2.5 X
institutional upper limit of normal

- Creatinine within normal institutional limits OR creatinine clearance > 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.

7. Patients must have weight loss ≤ 10% over the past three months.

8. Women of child-bearing potential and men will be asked to use adequate contraception.

9. Patients must have the ability to understand and the willingness to sign a written
informed consent document.

Exclusion Criteria:

1. Patients may not have had prior thoracic radiation at any time, or prior chemotherapy
for the study cancer at any time.

2. Patients may not be receiving any other investigational agents for the study cancer.

3. Patients may not have evidence of brain metastases on baseline CT scan or MRI.

4. Patients may not have measurable gross disease in the thorax <4 cm in any one
continuous dimension.

5. Patients may not have a cytologically positive pleural effusion.

6. Patients may not have a prior invasive malignancy (unless disease-free for at least 3
years).

7. Patients may not have had surgical resection of the present cancer.

8. Women who are pregnant or breastfeeding will be excluded.

9. Patients must not have any co-morbidity with life expectancy ≤ 6 months, or any
uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

10. Patients must not have severe lung disease defined by a history of severe chronic
obstructive pulmonary disease (COPD) requiring 3 or more hospitalizations over the
past year, or history of interstitial pneumonitis.

11. Patients must not have any concurrent active malignancy.

12. Patients must not have evidence of metastatic disease.