PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To estimate the efficacy (based on post-treatment PET findings) of dose-painted
intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy for locally-advanced
non-small cell lung cancer (LA-NSCLC).

SECONDARY OBJECTIVES:

I. To estimate the efficacy (based on clinical endpoints including locoregional control
[LRC], disease-free survival [DFS], and overall survival [OS]) of dose-painted IMRT with
concurrent chemotherapy for LA-NSCLC.

II. To evaluate the safety of dose-painted IMRT with concurrent and adjuvant chemotherapy for
LA-NSCLC.

III. To evaluate the utility of post-treatment PET/computed tomography (CT) imaging as a
predictor of clinical outcomes following treatment with this novel approach.

IV. To explore, in a preliminary manner, whether metabolomic markers in the blood and urine
prior to and during the course of treatment are associated with treatment response, clinical
endpoints, and treatment-related adverse events such as radiation pneumonitis.

OUTLINE:

RADIATION THERAPY: Patients undergo PET-adjusted IMRT or proton beam radiation therapy five
days a week for 5 weeks.

CONCURRENT CHEMOTHERAPY: Patients receive carboplatin intravenously (IV) over 3 hours and
paclitaxel IV over 1 hour once weekly for 5 weeks beginning week 1 of thoracic radiotherapy.

CONSOLIDATION CHEMOTHERAPY: Beginning approximately 4-6 weeks after the completion of all
radiation therapy and when esophagitis and chemotherapy-induced neuropathy are grade 1 or
less, absolute neutrophil count (ANC) > 1500, and platelet count > 100,000, patients may
receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1. Treatment may
repeat every 21 days for up to 3 courses in the absence of disease progression or
unacceptable toxicity at the discretion of the treating physicians.

After completion of study treatment, patients are followed up at 12-16 weeks, 19 weeks, every
3 months for 2 years, and then every 6 months for a total of 5 years.

Inclusion Criteria:

- Pathologically proven (either histologic or cytologic) diagnosis of NSCLC with any of
the following stages (according to the American Joint Committee on Cancer [AJCC]
Staging Manual, 7th edition):

- Stage IIIA or IIIB

- Stage II NSCLC with medical contraindication to curative surgical resection

- Stage IV disease with solitary brain metastasis that has been treated radically
(eg: with surgical resection or stereotactic radiosurgery) and thoracic disease
that would be classified as stage II-III

- Appropriate diagnostic/staging workup, including:

- Complete history and physical examination

- Whole body PET/computed tomography (CT) scan within 42 days prior to study entry
demonstrating hypermetabolic pulmonary lesion(s) and/or thoracic lymph node(s),
with a maximum standardized uptake volume (SUV) > 6 for at least one lesion; if
PET/CT was obtained more than 42 days prior to study entry and is not repeated,
CT scan of the chest within 28 days prior to study entry demonstrating stable
disease is required

- Magnetic resonance imaging (MRI) of the brain or CT scan of the head with
contrast within 42 days prior to study entry

- Biopsy confirmation of suspected metastatic disease identified by PET/CT is
recommended

- Pulmonary function tests (PFTs) within 6 weeks of study entry are highly
recommended but not required

- No prior chemotherapy or thoracic radiotherapy for lung cancer

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Absolute neutrophil count (ANC) >= 1,500 cells/ul

- Platelets >= 100,000 cells/ul

- Hemoglobin >= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve
hemoglobin [Hgb] >= 9.0 g/dl is acceptable)

- Total bilirubin < 3.0 times the institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x the ULN

- Serum creatinine =< 1.5 x ULN or calculated creatinine clearance >= 50 ml/min (by
Cockroft-Gault formula)

- Women of childbearing potential must:

- Have a negative serum or urine pregnancy test within 72 hours prior to the start
of study therapy

- Agree to utilize an adequate method of contraception throughout treatment and for
at least 4 weeks after study therapy is completed

- Be advised of the importance of avoiding pregnancy during trial participation and
the potential risks of an unintentional pregnancy

- All patients must sign study specific informed consent prior to study entry

Exclusion Criteria:

- Pleural or pericardial effusion

- A patient with pleural effusion may be enrolled the effusion is sampled by
thoracentesis and cytology is negative or the effusion is seen on axial imaging
but not on chest x-ray and deemed too small to tap under CT or ultrasound
guidance

- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious) illness

- Women who

- Are unwilling or unable to use an acceptable method to avoid pregnancy for the
entire study period and for at least 4 weeks after cessation of study therapy

- Have a positive pregnancy test at baseline

- Are pregnant or breastfeeding

- Poorly controlled diabetes (defined as fasting glucose level > 200 mg/dL) despite
attempts to improve glucose control by fasting duration and adjustment of medications;
patients with diabetes will preferably be scheduled for PET/CT imaging in the morning,
and instructions for fasting and use of medications will be provided in consultation
with the patients' primary physicians