PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer
PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer
This phase II trial studies how well intensity modulated radiation therapy adjusted by
 positron emission tomography (PET) scanning together with combination chemotherapy works in
 treating patients with stage II-IV non-small cell lung cancer (NSCLC). Radiation therapy uses
 high energy x rays to kill tumor cells. In intensity-modulated radiotherapy, multiple beam
 angles and dozens of beam segments are used to deliver highly conformal radiation therapy.
 Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to
 stop the growth of tumor cells, either by killing the cells or by stopping them from
 dividing. Giving PET-adjusted IMRT together with combination chemotherapy may kill more tumor
 cells.
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