Concurrent Proton and Chemotherapy in Locally Advanced Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC)

A proton beam is made up of charged particles that have a well-defined range of penetration
into tissues. How deep it can penetrate is decided by both the beam's energy and the density
of the tissue through which it passes. As the proton beam penetrates the body, the particles
slow down, and the beam deposits its dose sharply near the end of its range. This is a
phenomenon known as the Bragg peak. By adjusting the Bragg peak, the doctor can deliver a
full, localized, uniform dose of energy to the treatment site while sparing the surrounding
normal tissues. The proton beam is ideal for treatments where organ preservation is very
important, such as lung cancer.

If you are found to be eligible to take part in this study, you will receive 37 treatments of
proton radiotherapy (Monday through Friday for 7 1/2 weeks). During the treatment, you will
lie still on a table for about 30-45 minutes per day in the same position. The proton machine
will deliver the dose according to the plan designed by the physician and controlled by a
computer. You will not feel, see, or smell anything during the proton beam delivery. While on
study, you will also be receiving weekly standard low-dose chemotherapy possibly followed by
full-dose chemotherapy.

During the treatment, you will be seen by a doctor and research nurse once a week to evaluate
possible side effects. You will have a physical exam and you will have a medical history.
About 2 teaspoons of blood will be drawn for routine tests.

You will be taken off study early if the disease gets worse or intolerable side effects
occur. After finishing the treatment, 6 week follow up is recommended after completion of
radiotherapy, then required every 3 months (+1 month) for 2 years, then every 6 months (+1
month) for 3 years, and then once a year for 2 years. You will have imaging tests (chest CT
or positron emission computed tomography (PET) scan) and routine blood tests (about 2
teaspoons) at the follow-up visits.

This is an investigational study. Proton radiotherapy is FDA approved for the treatment of
lung cancer. A total of 65 patients will be take part in this study. All will be enrolled at
MD Anderson.

Inclusion Criteria:

1. Histologically or cytologically documented NSCLC.

2. Inoperable stage IIIA (T1--3N2MO, T3N1MO) and IIIB (T1-3N3MO, T4NO-3MO) disease
excluding malignant pleural effusion.

3. Performance score Karnofsky Performance Status (KPS) 70-100, Weight loss: less or
equal to 10% in 6 months prior to diagnosis.

4. Patient consented for the protocol

5. Induction chemotherapy is allowed.

Exclusion Criteria:

1. Prior chest radiotherapy.

2. Previous or concomitant malignancy other than (a) curatively treated carcinoma in situ
of cervix, (b) basal cell carcinoma of the skin, (c) curatively treated superficial
transitional cell carcinoma of the urinary bladder, and (d) early stage tumor treated
more than 3 years ago for cure.

3. Pregnancy. Patients (men and women) of child bearing potential should use an effective
(for them) method of birth control throughout their participation in this study.

4. Off study criteria: a) If a patient is found to have distant metastasis during
treatment and/or immediate after the treatment (<60 days) indicating inaccurate cancer
stage, he or she will be taken off study. b) If a patient does not follow up at MD
Anderson and does not forward his or her medical records such as CT, PET/CT, pulmonary
function test (PFT) or pathology report as required by protocol, he or she will be
taken off study. c) If a patient does not have any required post-treatment evaluation
such as images, he or she will be taken off study.