TARCEVA (Erlotinib) in Combination With Chemoradiation in Patients With Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC)

Erlotinib is designed to block the activity of a protein called epidermal growth factor
(EGFR). EGFR is found on the surface of many tumor cells that may control tumor growth and
survival. This may stop tumors from growing.

Before you can start treatment on this study, you will have "screening tests." These tests
will help the doctor decide if you are eligible to take part in the study. You will have a
FEV1 (breathing test). You will have a complete physical exam, including measurement of vital
signs (blood pressure, heart rate, temperature, and breathing rate). Blood (about 2
tablespoons) will be drawn for routine tests. You will have a computed tomography (CT) scan
or magnetic resonance imaging (MRI) of the brain to check the status of the disease. You will
be required to have a positron emission tomography (PET) scan to locate the area of cancer
outside the chest and lymph glands. You will have either a CT scan or an MRI to measure the
size of the tumor(s). If there is positive finding of CT or MRI you will be taken off study.
You will have an electrocardiogram (ECG -- a test that measures the electrical activity of
the heart). If you have a significant history of cardiovascular disease, you will have a MUGA
scan and echocardiogram to test your heart function. Women who are able to have children must
have a negative urine or blood (about 2 teaspoons) pregnancy test before starting treatment.

You will have PET scan 1 month after completion of consolidation chemotherapy.

If you are found to be eligible to take part in this study, you will take erlotinib every day
for 7 weeks (except on the days you receive chemotherapy). The erlotinib tablets should be
taken at the same time each day, at least 1 hour before or 2 hours after a meal, with a small
glass (about 7 ounces) of water. If you are unable to swallow tablets, you may dissolve the
tablets in distilled water to drink.

You will receive radiation every day (Monday through Friday) for 7 weeks. You will also
receive chemotherapy through a needle in a vein once a week for 7 weeks. The chemotherapy
will include carboplatin and paclitaxel. Receiving chemotherapy will take about 6 hours
total.

You will receive consolidation therapy on weeks 11-17.

Treatment on this study will last 17 weeks. Once a week during that time, you will have blood
(about 2 tablespoons) drawn for routine tests. You will also have a CT scan of the chest
within about 4 weeks from beginning the study, 2 months after finishing therapy, and then
every 6 months after that for 2 years. The CT scans are used to check the status of the
disease.

You will be taken off study if the disease gets worse or intolerable side effects occur. In
this case, you would not receive erlotinib anymore but would continue standard chemotherapy
and radiation therapy.

You will be asked to come in to the clinic for follow-up visits to check on your recovery
from treatment. The follow-up visits will be at the end of all treatment, 1 month after
treatment, and then once a month for as long as your doctor feels it is necessary. Once your
side effects have become less severe, you will be asked to come in to the clinic for
follow-up visits every 3 months for 2 years, and then every 4 months for the following 2
years after that. You will have a physical exam, and your medical history will be recorded.
You will be asked about any side effects you may have. Blood (about 2 tablespoons) will be
drawn for routine tests. You will have a PET scan.

You have the right to leave the study at any time. If you choose to stop participating in
this study, you should contact the study chair and/or research nurse. Your doctor may decide
to take you off this study if your medical condition gets worse and/or you are unable to
comply with study requirements.

At the end of the study you will not be automatically notified of the research findings. If
you wish to learn about the results, however, you may request them from the study chair.

This is an investigational study. All three study drugs are commercially available.
Carboplatin, and paclitaxel are FDA approved for the treatment of NSCLC, but their use in
combination with erlotinib is not. Erlotinib is FDA approved for some uses, but it has not
been approved by the FDA to treat lung cancer patients like yourself who have not yet
undergone chemotherapy; however, the FDA has permitted its use in this research study.
Carboplatin and paclitaxel are considered standard of care treatment and you would probably
be treated with these drugs or similar drugs even if you decided not to be in the study. Up
to 48 patients will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Histologically or cytologically documented NSCLC, including squamous cell carcinoma,
adenocarcinoma (including bronchoalveolar cell), and large cell anaplastic carcinoma
(including giant and clear cell carcinomas) and poorly differentiated (not otherwise
specified, NOS) non-small cell lung cancer; totally resected tumors are excluded. ·

2. Patients must be M0;

3. Patients with Tl or T2 disease with N2 or T3N1-2 disease (Stage IIIA) are eligible if
they are deemed inoperable. Patients with T4 with any N or any T with N2 or N3 disease
are eligible if unresectable. Radiographic evidence of mediastinal lymph nodes > 2.0
cm in the largest diameter is sufficient to stage N2 or N3 disease. If the largest
mediastinal node is < 2.0 cm in diameter and this is the basis for stage III disease,
then at least one of the nodes must be proven positive cytologically or
histologically;

4. Measurable disease is required

5. Patients with tumors adjacent to a vertebral body are eligible as long as all gross
disease can be encompassed in the radiation boost field. The boost volume must be
limited to < 50% of the ipsilateral lung volume.

6. Patients must be greater than or equal to 18 years of age;

7. Patients with Zubrod performance status 0-1

8. Adequate hematologic function defined as: ANC greater than or equal 1,500/mm^3,
platelets greater than or equal 100,000/mm^3, and hemoglobin greater than or equal 9
g/dL (prior to transfusions); adequate hepatic function defined as: total bilirubin
less than or equal to 1.5 mg/dl, SGOT or SGPT less than or equal to 3 x ULN, adequate
renal function defined as a serum creatinine level less than or equal to 2.0 mg/dl,
alkaline phosphatase less than or equal to 2.5 x ULN, glucose less than or equal to 2
x ULN;

9. FEV1 with greater than or equal to 1000 cc;

10. Patients with weight loss less than or equal to than
11. Patients with a pleural effusion that is a transudate, cytologically negative and
nonbloody are eligible if the radiation oncologists feel the tumor can still be
encompassed within a reasonable field of radiotherapy. If a pleural effusion can be
seen on the chest CT but not on CXR and is too small to tap, the patient is eligible.

12. If patients had exploratory thoracotomy, they must have recovered from the procedure.
Exploratory Thoracotomy and beginning of treatment should be within one month.

13. Women of childbearing potential (A woman of child-bearing potential is a sexually
mature woman who has not undergone a hysterectomy or who has not been naturally
postmenopausal for at least 24 consecutive months [i.e., who has had menses at any
time in the preceding 24 consecutive months]) and male participants must practice
effective contraception (oral, injectable, or implantable hormonal contraceptive;
tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or
vasectomized partner) throughout the study and for four weeks after completion of
treatment.

14. For women of childbearing potential, a urine or blood pregnancy test must be performed
within 48 hours prior to the start of protocol treatment;

15. Medical Oncology and Radiation Oncology consults and approval.

16. Patients must sign a study-specific consent form prior to study entry.

Exclusion Criteria:

1. Prior systemic chemotherapy and/or thoracic radiotherapy for any reason and/or
surgical resection of present cancer;

2. Exudative, bloody, or cytologically malignant effusion or effusion that are exudative
and/or bloody and are suggestive or malignant involvement.

3. Prior therapy with any other drug that targets the EGFR pathway,

4. Active pulmonary infection not responsive to conventional antibiotics;

5. History of interstitial lung disease;

6. History of severe COPD requiring greater than or equal to 3 hospitalizations over the
past year;

7. Significant history of cardiac disease, i.e., uncontrolled hypertension, unstable
angina, uncompensated congestive heart failure, myocardial infarction within the past
year, or cardiac ventricular arrhythmias requiring medication; patients with left
ventricular ejection fraction (LVEF) below the institutional range of normal (50-70%)
on a baseline multiple gated acquisition (MUGA) scan or echocardiogram.

8. Patients with > grade 1 neuropathy;

9. Evidence of malignancy in the past 3 years except for adequately treated basal cell or
squamous cell skin cancer, in situ cervical cancer, or other in situ cancers;

10. Women who are pregnant or breast feeding, as treatment involves unforeseeable risks to
the participant, embryo, fetus, or nursing infant; women with a positive pregnancy
test on enrollment or prior to study drug administration;

11. Women of childbearing potential and male participants who are unwilling or unable to
use an acceptable method of contraception (oral, injectable, or implantable hormonal
contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with
spermicide; or vasectomized partner) throughout the study and for four weeks after
completion of treatment or those who are using a prohibited contraceptive method
(methods with unknown efficacy).

12. Patients who currently are participating in other clinical trials and/or who have
participated in other clinical trials in the previous 30 days. Clinical trials
involving administration of investigational agents or interfering with the safe
conduct of this trial. All clinical trials would exclude observational trials which
would not interfere with the endpoints of our study.