Phase I IGART Study Using Active Breathing Control and Simultaneous Boost for Patients With NSCLC

OUTLINE: This is a dose-escalation study of IGART.

Patients undergo IGART using active breathing control (ABC) 5 days a week for 7 weeks, for a
total of 33 fractions with simultaneous integrated volume adapted boost (SIVAB) during
fractions 26-33. Patients also receive paclitaxel intravenously (IV) over 1 hour and
carboplatin IV over 30 minutes once a week for 6 weeks.

After completion of study treatment, patients are followed up periodically for 5 years.

Inclusion Criteria:

- Histologically-proven (by biopsy or cytology), unresectable or inoperable lung cancer
of the following histologic types: squamous cell carcinoma, adenocarcinoma, large
cell carcinoma, non-small cell carcinoma not otherwise specified.

- The tumor stage must be Stage IIA-IIIB (AJCC 7th edition). See
http://aboutcancer.com/AJCC 7th lung 1.gif and http://aboutcancer.com/AJCC 7th lung
2.gif for staging.

- All detectable tumor must be encompassed by radiation therapy fields.

- 18-fluorodeoxyglucose PET is required for staging and treatment planning.

- Atelectasis, if present, must involve less than a complete lung.

- Laboratory values:

- Neutrophils >1500/µL

- Platelets >100,000/µL

- Bilirubin < 1.5 mg/dL

- Aspartate aminotransferase (AST; formerly serum glutamic oxaloacetic
transaminase [SGOT]) < 2x upper limit normal

- Alanine aminotransferase (ALT; formerly serum glutamic pyruvic transaminase
[SGPT]) < 2x upper limit normal

- Serum creatinine < 2.0 mg/dL

- Glomerular filtration rate (GFR) calculated (kidney function test) within 30
days must be ≥ 59 mL/min

- Pulmonary function test (PFT) with FEV-1 ≥ 1.0 L/sec

- Plan of curative radiotherapy with or without concurrent chemotherapy.

- Karnofsky Performance Scale score of ≥ 70%.

- Age ≥ 18 years old.

- Measurable disease on the planning CT.

- Patient must have a completed IMRT plan to 66 Gy in 2 Gy fractions with ≥ 95% of the
PTV covered by the prescription dose, and the attending physician must have reviewed
and approved the DVHs as follows:

- total lung V20 Gy ≤ 30%

- mean esophageal dose ≤ 34 Gy

- esophageal planning organs-at-risk volume (PRV) V60 Gy ≤ 30%

- heart V40 Gy ≤ 50%

- maximum brachial plexus dose ≤ 66 Gy

- maximum spinal cord PRV dose ≤ 50 Gy

- maximum aorta dose ≤ 66 Gy

- maximum main bronchus dose ≤ 66 Gy

- maximum dose ≥ 66 Gy allowed in only one lobar bronchus.

- Ability to understand and the willingness to sign a written informed consent
document.

Exclusion Criteria:

- Complete tumor resection, recurrent disease, or those patients eligible for
definitive surgery.

- Prior radiation therapy to the thorax.

- Previous chemotherapy or previous biologic response modifiers for current lung cancer
or within the past 5 years.

- Clinically significant pleural effusions, pericardial effusions, or superior vena
cava syndrome.

- Oxygen supplementation required during therapy.

- Involvement of the brachial plexus, or infiltration of the aorta, heart, or
esophagus.

- Tumors that affect more than one lobar bronchus, except the second involved bronchus
in the right middle lobe bronchus.

- Unable to perform the BH procedures, unless tumor motion is ≤ 3 mm.

- Myocardial infarction within the last 6 months, symptomatic heart disease,
uncompensated chronic obstructive pulmonary disease (COPD), or uncontrolled
bronchospasms.

- History of a prior malignancy from which the patient has not been disease free for a
minimum of 2 years, other than adequately treated basal/squamous skin cancer or in
situ cervix cancer or other in situ malignancy.

- Pregnant or lactating women.