MRI Adaptive Replanning Using ViewRay

This study is a single-arm phase II study of adaptive radiotherapy using ViewRay MRI based
imaging in locally Advanced non-small cell lung cancer patients. Randomization is not
applicable.

Inclusion Criteria:

1. Patient must have primary lung tumor identified on MRI, histologically proven to be
NSCLC.

2. Patients must be clinical AJCC stage IIIA or IIIB (AJCC 7th ed) with non-operable
disease; evaluated by a multidisciplinary treatment team including at least 1 thoracic
surgeon within 8 weeks prior to registration.

3. Patients with multiple, ipsilateral pulmonary nodules (T3, or T4) are eligible

4. Minimum diagnostic workup to include:

- History/physical examination, including documentation of weight, within 8 weeks
prior to registration (2 weeks optimal)

- Diagnostic CT scan for staging and RT plan within 4 weeks prior to registration;

- CT scan or sim CT of chest and upper abdomen (IV contrast is recommended unless
medically contraindicated) within 6 weeks prior to registration;

- CT scan of the brain (contrast is recommended unless medically contraindicated)
or MRI of the brain within 6 weeks prior to registration

- Able to tolerate repeated MRI imaging

- Pulmonary function tests, including diffusing capacity of the lung for carbon
monoxide (DLCO), within 6 weeks prior to registration; patients must have forced
expiratory volume in one second (FEV1) ≥ 1.2 Liter or ≥ 50% predicted without
bronchodilator;

- Zubrod Performance Status 0-1 within 2 weeks prior to registration

- Age ≥ 18;

- Complete blood count (CBC)/differential obtained no more than 8 weeks prior to
registration on study, with adequate bone marrow function defined as follows:

- White blood cell (WBC) ≥ 4000/ml

- Absolute neutrophil count (ANC) ≥1,800 cells/mm

- Platelets ≥100,000 cells/mm

- Hemoglobin ≥ 10.0 mg/dl (Note: the use of transfusion or other intervention
to achieve this level is acceptable)

- Serum creatinine, blood urea nitrogen, alanine aminotransferase (ALT), aspartate
aminotransferase (AST), Alk Phos, total bilirubin, serum electrolytes (eg.
Sodium, potassium, chloride, bicarbonate, calcium), glucose, total protein,
albumin will be drawn no greater than 8 weeks prior to enrollment.

- Serum creatinine of 1.5mg or less; serum bilirubin of 2.0mg or less;
creatinine clearance of 60ml/min or greater no more than 4 weeks prior to
registration (Note: calculated creatinine clearance is permissible. If the
creatinine clearance is greater than 60ml/min, then a serum creatinine of up
to 1.8mg is allowable at the discretion of the PI

- Serum pregnancy test for female patients of childbearing potential, ≤8 weeks
prior to enrollment; women of childbearing potential and male participants must
practice adequate contraception on trial

- Patients must be able to provide study-specific informed consent prior to study
entry

- Patients must agree to have their biopsy tissue and blood banked for future
molecular studies

Exclusion Criteria:

1. Patients with any component of small cell lung carcinoma are excluded

2. Evidence of distant metastases.

3. Patients with evidence of a malignant pleural or pericardial effusion.

4. Previous systemic chemotherapy (for any cancer) or pelvic radiation therapy

5. A prior or concurrent malignancy of any other site or histology unless the patient has
been disease free for greater than or equal to five years except for nonmelanoma skin
cancer and/or stage T1a prostate cancer or carcinoma in situ of the uterine cervix.

6. Prior radiotherapy that would result in overlap of radiation fields

7. Patients taking drugs with potential nephrotoxicity or ototoxicity (such as
aminoglycosides)

8. Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception; this exclusion is
necessary because the treatment involved in this study may be significantly
teratogenic

9. Prior allergic reaction to the study drug(s) involved in this protocol

10. Patients with T4 disease with radiographic evidence of invasion of a large pulmonary
artery and tumor causing significant narrowing and destruction of that artery are
excluded.

11. Severe active co-morbidity:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months

- Transmural myocardial infarction within the last 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration

- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of registration

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
(Note: laboratory tests for liver function and coagulation parameters are not
required for entry into this protocol)

- Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease
Control and Prevention (CDC) definition (Note: HIV testing is not required for
entry into this protocol) The need to exclude patients with AIDS from this
protocol is necessary because the treatments involved in this protocol may be
significantly immunosuppressive. Protocol-specific requirements may also exclude
immune-compromised patients