Study Assessing the Efficacy of Local Consolidative Therapy for Non-Small Cell Lung Cancer Patients With Induced Oligometastatic Disease

In order to be eligible for this study, you will either be scheduled to receive or have
already received induction chemotherapy without the disease getting worse.

Study Groups:

If the disease has gotten worse after induction chemotherapy, you will no longer be eligible
to participate in this study and the study doctor will talk to you about other options.

If the disease has not gotten worse after you have completed induction chemotherapy, you will
be randomly assigned (as in the flip of a coin) to 1 of 2 groups:

Group 1 will immediately receive local consolidation therapy (LCT) after induction
chemotherapy. LCT is radiation, surgery, or both. If you are assigned to the LCT group, the
study doctor will decide if you will have radiation alone, surgery alone, or radiation
combined with surgery.

Group 2 will receive delayed or no LCT after induction chemotherapy. The treatment you
receive will depend on what the study doctor thinks is in your best interest.

Group 1 - Immediate Local Consolidation Therapy (LCT):

Each study cycle is approximately 8 weeks, but may vary if your doctor thinks it is in your
best interest.

Surgery:

You will be given a separate consent form to sign that describes the surgical procedure and
its risks in more detail. The type of surgery you will have will depend on the status of the
disease.

Radiation Therapy:

About 1-2 weeks before you begin radiation therapy, you will have a procedure called a
simulation. During the simulation, the exact location for the radiation therapy will be
planned. The simulation procedure takes about 1 hour.

You will receive radiation daily (Monday through Friday) for a period lasting from 1 day up
to 8 weeks, depending on the location and status of the disease. The radiation only takes a
few minutes to administer each day. However, you will be asked to allow about 1 hour each day
for the procedure.

You will be given a separate consent form to sign that describes the radiation therapy and
its risks in more detail. The type of radiation therapy you will have will depend on the
status of the disease.

Group 2 - Delayed/No Local Consolidation Therapy (LCT):

If you are in Group 2, you will not be receiving surgery or radiation therapy right after
induction chemotherapy. If you are randomized to this arm, you will receive either systemic
therapy (i.e. chemotherapy) or observation. The care you receive will depend on what your
doctor thinks is in your best interest.

Chemotherapy:

Each study cycle is approximately 8 weeks, but may vary if your doctor thinks it is in your
best interest.

If you receive chemotherapy, either after induction chemotherapy is complete or after
receiving LCT, your treating physician will decide the type of chemotherapy you will receive.

You will be given a separate consent form to sign that describes the chemotherapy and its
risks in more detail. The type of chemotherapy you will have will depend on the status of the
disease.

Study Visits:

If the study doctor thinks it is needed, the following tests and procedures may be performed
before and/or during chemotherapy and/or radiation

- A physical exam will be performed, including measurement of your vital signs.

- Your performance status will be recorded.

- Your medical history will be recorded.

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

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

During chemotherapy, if the study doctor thinks it is needed, you may also have a computed
tomography (CT) scan, positron emission tomography (PET) scan, and/or magnetic resonance
imaging (MRI) scan to check the status of the disease. These imaging scans will be done about
every 6-8 weeks during the first year of the study to check the status of the disease.

Length of Treatment:

You may continue receiving the study treatment for up to 2 years or as long as the doctor
thinks it is in your best interest. You may no longer be able to receive the study treatment
if the disease gets worse, if intolerable side effects occur, or if you are unable to follow
study directions.

Your participation on the study will be over after the follow-up visits.

Follow-Up Visits:

All study participants will have follow-up visits after the surgery is complete, or after the
last dose of radiation or chemotherapy, depending on which treatment you were assigned to.
During each follow-up visit, you may have the following tests and procedures performed if the
study doctor thinks it is needed:

- You will have a physical exam, including measurement of your vital signs (blood
pressure, heart rate, temperature, and breathing rate).

- Your performance status will be recorded.

- Your medical history will be recorded.

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

- You will have lung function tests to check the status of the disease.

- You will have a CT scan to check the status of the disease.

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

- Your oxygen level will be measured using a small device that is placed on the tip of
your finger.

Other Information:

If at any time while you are on study your treating physician thinks it is in your best
interest, you may be switched to the other treatment option (LCT to no LCT or vice versa).

This is an investigational study. The combination of LCT after chemotherapy for the treatment
of NSCLC is being used for research purposes only.

Up to 94 patients who are eligible to be randomized will be enrolled in this study. Up to 85
of these patients will be enrolled at MD Anderson.

Inclusion Criteria:

1. STEP 1 Enrollment: The patient has a diagnosis of pathologically confirmed NSCLC by
tumor biopsy and/or fine-needle aspiration. Mixed tumors will be categorized by the
predominant cell type.

2. The patient has a diagnosis of American Joint Committee on Cancer (AJCC) 7th Edition
stage IV NSCLC.

3. Three or less metastatic lesions (not sites). * each lesion (including a satellite
nodule) will individually be counted as one, and intrathoracic lymph node involvement
(defined here as hilar, mediastinal, or supraclavicular nodes, N1-N3) will
collectively be counted as one. In addition, patients can receive treatment to CNS
lesions or other symptomatic lesions requiring urgent local therapy prior to
randomization, but these lesions will be counted towards the total number after
chemotherapy, and patients will only be eligible if there are remaining sites amenable
to local therapy after up-front systemic therapy.

4. Standard induction chemotherapy planned defined as: *At least 4 cycles of platinum
doublet chemotherapy for metastatic disease (with or without bevacizumab), * if the
patient is known to be EGFR mutation positive, erlotinib, afatinib, or gefitinib for
>/=3 months, or * for patients with known EML4-ALK fusions, crizotinib for >/=3 months

5. STEP 2 Enrollment and Randomization: The patient has a diagnosis of pathologically
confirmed NSCLC by tumor biopsy and/or fine-needle aspiration. Mixed tumors will be
categorized by the predominant cell type.

6. The patient has a diagnosis of American Joint Committee on Cancer (AJCC) 7th Edition
stage IV NSCLC.

7. Completion of standard induction chemotherapy planned defined as: *At least 4 cycles
of platinum doublet chemotherapy for metastatic disease (with or without bevacizumab),
*if the patient is known to be EGFR mutation positive, erlotinib, afatinib, or
gefitinib for >/=3 months, or *for patients with known EML4-ALK fusions, crizotinib.
Note that it is not mandatory to check EGFR mutation or EML4-ALK status prior to
entry, but patients that receive options 2 or 3 should have had these molecular tests
performed.

8. Less than or equal to three metastatic lesions and no evidence of disease progression
based on RECIST criteria. Note that patients that had >3 metastatic lesions in Step 1
may be eligible for enrollment in Step 2 if the number of metastatic sites is reduced
to three or less.

9. The patient's ECOG performance status is
10. The patient has adequate hematologic function as defined by an absolute neutrophil
count (ANC) >/= 1,500/mm^3, platelet count >/= 100,000/mm^3, WBC >/= 3,000/ mm^3, and
hemoglobin >/= 9 g/dL within 3 weeks of study entry.

11. The patient must be a suitable candidate for LCT (radiotherapy and/or surgery) to
every site of disease, as determined by the treating physician(s). Consultation with a
multidisciplinary team, including a medical oncologist, radiation oncologist, and
thoracic surgeon, is encouraged but not required.

12. Concurrent chemoradiation is permitted as consolidative therapy. The following
concurrent therapies are permitted: Tyrosine kinase inhibitors (i.e. erlotinib) - can
be delivered with both hypofractionated >/=3 Gy per fraction) and standard
fractionated radiation therapy (<3 Gy per fraction); platinum-based chemotherapy -
standard fractionated radiation therapy (<3 Gy per fraction)

13. Bevacizumab will not be permitted within 2 weeks of the initiation of the radiation
therapy course

14. Treatment to central nervous system lesions, such as the brain or spine (prior to
first line systemic therapy), or symptomatic lesions requiring urgent palliative
radiation, is permitted prior to randomization, in which case the patient would be
randomized to treatment of other metastatic sites or the primary sites (based on the
disease remaining after first-line treatment). These treated lesions should be counted
towards the total number of metastases at the time of enrollment.

15. The patient is >/= 18 years of age.

16. The patient has signed informed consent.

17. Women of childbearing potential must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) for the duration of study participation
and for six (6) months after discontinuation of the study drugs. Childbearing
potential will be defined as women who have had menses within the past 12 months, who
have not had tubal ligation, hysterectomy or bilateral oophorectomy. Should a woman
become pregnant or suspect that she is pregnant while participating in this study, she
should inform her treating physician immediately. The patient, if a man, agrees to use
effective contraception or abstinence for the duration of study participation and for
six (6) months after discontinuation of the study drugs.

Exclusion Criteria:

1. STEPS 1 and 2 and randomization: The patient has a history of uncontrolled angina,
arrhythmias, or congestive heart failure.

2. Patients with a history of malignant pleural effusions are not eligible. Pleural
effusions considered by the investigator too small for a diagnostic thoracentesis are
permissible.

3. patient is pregnant (confirmed by serum b-HCG if applicable) or is breastfeeding.

4. Presence of significant third space fluid which cannot be controlled by drainage.