Trial of Image-Guided Adaptive Conformal Photon vs Proton Therapy, With Concurrent Chemotherapy, for Locally Advanced Non-Small Cell Lung Carcinoma: Treatment Related Pneumonitis and Locoregional Recurrence

There are 2 types of radiation treatment being used in this study. One type of treatment is
proton therapy. Proton therapy is a type of radiation therapy that uses a beam of proton
particles (similar to getting an x-ray) to send radiation inside the body to the tumor. The
other type of treatment is Image-Guided Adaptive Photon Therapy (IGAPT). IGAPT is a therapy
that uses images to help guide the delivery of photon therapy to the tumor. Both of these
types of radiation treatment are believed to help doctors to give a full dose of radiation
treatment to the tumor while not damaging as much of the healthy tissue around it.

Study Groups:

If you are found to be eligible to take part in this study, you will go through the standard
radiation treatment planning procedure, called the "marking session." After the marking
session, a standard photon therapy plan (called Intensity Modulated Radiation Therapy, or
IMRT) and a proton plan will be developed. If the radiation oncologist thinks that both the
photon and proton plans are acceptable, you will then be randomly assigned to 1 of 2 groups.
Participants in Group 1 will receive photon therapy. Participants in Group 2 will receive
proton therapy.

The first 20 participants will have an equal chance to be assigned to either group. After at
least 20 participants have been enrolled and there has been at least 1 occurrence of
pneumonitis and/or tumor recurrence in each treatment Group, the risk of pneumonitis and/or
tumor recurrence in all previous participants will be evaluated for each treatment Group, and
that information will be used to calculate the chances of being assigned to either Group 1 or
Group 2. This calculation will be updated after each occurrence of pneumonitis and/or tumor
recurrence and after each participant returns for a follow-up visit. Once these calculations
are begun, everyone who joins the study from that point on will be more likely to be assigned
to the treatment Group that appears to be better in terms of pneumonitis and/or tumor
recurrence.

If the tumor is too large and the standard radiation treatment plan created during the
marking session is found not to be acceptable, and the radiation oncologist thinks radiation
treatment it is necessary, you will still remain on study and be assigned to a third group.
If you are assigned to Group 3, you will receive proton or photon treatment at a lower dose
level and/or reduced length of radiation.

If you are assigned to Group 2 and your insurance provider denies reimbursement, you may
chose not to receive proton therapy and receive photon therapy instead. If you chose to
receive photon therapy, you will be in Group 4.

Radiation Therapy Administration:

Both radiation therapy treatments (photon and proton) are given through a radiation machine
called an accelerator. The radiation therapy administration process is very similar to the
way that a CT scan is performed. You will lay on a table and the treatment machine rotates
around you without touching your body. Each daily treatment should take about 20-30 minutes
to complete. Most of this time is used to position you correctly before the machine is turned
on. The actual time used to give the radiation should take about 3-5 minutes each day.

While you are on this study and if you are in Groups 1 or 2, you will receive a total of 37
radiation treatments. Radiation is given 5 days a week for about 7 1/2 weeks.

If you are in Group 1, you will receive photon radiation treatment in the main hospital.

If you are in Group 2, you will receive proton therapy in the proton treatment center (PTC).

If you are in Group 3, you will receive either photon or proton therapy, whichever your
doctor decides is better for you, for 6-7 1/2 weeks. If your doctor decides that photon
therapy is better you will receive your treatment in the main hospital. If your doctor
decides that proton therapy is better you will receive your treatment in the Proton Therapy
Center.

If you are in Group 4, you will receive Photon radiation treatment in the main hospital.

Chemotherapy:

You will receive carboplatin and paclitaxel chemotherapy 1 time a week over 7 weeks. Each
treatment will last 3-4 hours. Paclitaxel will be given by vein over 1 hour and carboplatin
will be given by vein over 30 minutes. You will receive this chemotherapy combination with
radiation therapy, as part of your treatment on this study.

Your chemotherapy may also be decided by your treating medical oncologist as long as the
therapy is allowed by the study.

Study Visits During Chemoradiation:

At least 1 time each week for all study participants, you will have study tests performed.
During this weekly study visit, the following tests and procedures will be performed:

- You will have a physical exam.

- You will be asked about any side effects you may have experienced.

- Blood (about 2 teaspoons) will be drawn for routine tests.

If the study doctor thinks it is needed, you will have a PET/CT scan performed to check the
status of the disease during Week 4 or 5 of treatment.

Length of Study:

You will remain on study as long you are benefiting. You will be taken off study early if the
disease gets worse, you experience intolerable side effects, or your doctor thinks that it is
no longer in your best interest to receive the study treatment.

Follow-Up Visits:

After you have completed chemoradiation, the study staff or study nurse will contact you 1
time each month to ask you about any symptoms you may have until 6 months after
chemoradiation. Each phone call should last about 10 minutes.

You will have your first follow-up visit 4-8 weeks after you have completed chemoradiation.
You will have additional follow-up visits every 3-4 months for 3 years, every 6 months for
the next 2 years, and then 1 time every year after that.

At the first and second follow-up visit the following tests and procedures will be performed:

- You will have positron emission tomography (PET)/computed tomography (CT) scans and
single proton emission tomography (SPECT) scans to check the status of your lungs and
heart if the radiation or medical oncologist thinks it is necessary.

- Blood (about 1 teaspoon) will be drawn for routine tests.

If the radiation oncologist or medical oncologist thinks it is needed, at the follow-up
visits, you will have breathing function tests performed to check your lung function for up
to 1 year after the study treatment is complete. For this test, the radiation oncologist,
medical oncologist or study nurse will have you breathe into a special machine. The radiation
oncologist or medical oncologist will decide how many tests are to be performed each time.

PET/CT and SPECT scans will be performed again at any time the radiation oncologist or
medical oncologist thinks they are needed.

Other tests may be performed if the study doctor (radiation oncologist, medical oncologist,
surgeon or pulmonologist ) thinks they are needed.

This is an investigational study. Both proton radiotherapy and IGAPT are FDA approved for the
treatment of lung cancer.

Up to 250 patients will take part in this multicenter research study. Up to 205 will be
enrolled at M. D. Anderson.

Inclusion Criteria:

1. Pathologically proven, unresected, locoregionally advanced NSCLC without evidence of
hematogenous metastases (stage II-IIIB disease according to the 7th edition of the
AJCC Staging Manual) with exception as defined by inclusion #2).

2. Patients with solitary brain metastasis without sign of progression in the brain at
the time of registration will be eligible for this trial if there is clinical
indication for concurrent chemoradiation to the primary disease in the lung.

3. Suitability for concurrent chemoradiation therapy per treating radiation oncologists
or treating medical oncologist's: A) Karnofsky performance score of >/= 70, or ECOG
0-1 B) Unintentional weight loss
4. Receipt of induction chemotherapy followed by referral for concurrent chemoradiation
is allowed for this protocol.

5. Measurable disease on chest x-ray, contrast-enhanced CT, or PET scan.

6. Locoregional recurrence after surgical resection, if suitable for definitive
concurrent chemoradiation is allowed for this protocol.

7. Forced expiratory volume in the first second (FEV1) >/= 1 liters.

8. Fluorodeoxyglucose (FDG) -PET scan within 3 months before registration. The
pretreatment (diagnostic) PET/CT should, whenever possible, be performed together with
the 4-D CT simulation. PET images acquired either at the time of simulation or
acquired separately should be registered with the planning CT to assist in tumor
delineation.

9. Standard pretreatment evaluations (as decided by treating radiation oncologist,
medical oncologist, surgeons or pulmonologist), to include MRI or CT scan of the
brain, contrast CT scan of the thorax and upper abdomen, Whole-body PET/CT, pulmonary
function tests, lung and cardiac single proton emission computed tomography (SPECT),
liver function tests (LFT), blood chemistry, renal function tests, and complete blood
count.

10. Age >/= 18 years but
11. A signed specific informed consent form before study entry.

Exclusion Criteria:

1. Small cell histology.

2. Prior thoracic radiotherapy to regions that would result in overlap of radiation
therapy fields.

3. Pregnancy (female patients of childbearing potential must practice appropriate
contraception).

4. Enrollment in a clinical trial that specifically excludes IGAPT treatment.

5. Body weight exceeds the weight limit of the treatment couch.

6. Oxygen dependent due to preexistent lung disease (COPD, emphysema, lung fibrosis).