Feasibility Study of SBRT Plus Chemotherapy for Non-Small Cell Lung Carcinoma

PRIMARY OBJECTIVES:

I. To determine the safety/feasibility of delivering chemotherapy after definitive
stereotactic body radiation therapy (SBRT) for selected stage/situations of non-small cell
lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To determine the 1-year progression free survival in the sub-population of patients with
stage IB/II NSCLC, i.e. the "curative intent" subgroup of patients.

OUTLINE:

Patients undergo stereotactic body radiation therapy every other day for up to 14 days for a
total of 5 fractions. After a break period of about 30 days, patients will then start
chemotherapy. Patients will receive carboplatin intravenously (IV) over 30-40 minutes on day
1 and paclitaxel albumin-stabilized nanoparticle formulation IV over 30-40 minutes on days
1, 8, and 15. Treatment repeats every 21 days for up to 4 courses in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 year.

Inclusion Criteria:

- Patients must have pathologic diagnosis of non-small cell lung carcinoma (NSCLC), by
either histologic biopsy, or cytologic evidence; highly suspicious cytology (i.e.
abnormal cells suspicious for malignancy) is acceptable, in the setting of a strongly
positive computed tomography (CT)/positron emission tomography (PET) (standardized
uptake value [SUV] > 5.0)

- Patients must be considered appropriate for stereotactic body radiation therapy
(SBRT); this is determined on an individualized basis, by the prospective
multidisciplinary tumor board, that includes representation from surgical, radiation
and medical oncology; criteria for appropriateness for SBRT include all of the
following:

- Stage I/II non-small cell lung carcinoma (NSCLC) - no evidence of distant
metastases (patients with up to three lung nodules may be considered to have
'multiple primary' lung cancer rather than metastatic lung cancer and thus will
be eligible; if a lymph node(s) ≥ 2 cm and/or PET-SUV ≥ 4.0 is identified,
biopsy must be performed (and be negative) for the patient to be eligible;
patients thought to have M1b disease, or malignant pleural/pericardial effusions
are not eligible

- Staging including CT chest, PET/CT must be up-to-date, i.e. within 6 weeks prior
to registration; brain imaging (contrast-enhanced magnetic resonance imaging
[MRI] or CT) is suggested for all patients, but is only mandatory for patients
with abnormal neurologic exam

- Tumor size ≤ 7 cm in greatest dimension based upon an up-to-date CT (and/or
CT/PET) within 6 weeks prior to enrollment onto the study; radiation therapy
treatment planning imaging is acceptable)

- The patient must not be a candidate for (or declines because of high risk)
surgical resection because of medical comorbidity/risk; the patient must have
undergone an evaluation by an experienced thoracic surgeon within 12 weeks prior
to registration; standard justification criteria may include forced expiratory
volume in 1 second (FEV1) < 40% predicted; predicted postoperative FEV1 ≤ 30%
predicted; diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 60%
predicted; pulmonary hypertension (estimated ≥ 40 mm Hg); poor cardiac function
(ejection fraction [EF] ≤ 40%); Medical Research Council (MRC) dyspnea scale ≥ 3
(corresponds to inability to walk at least 100 yards without rest); baseline
hypoxemia (partial pressure of oxygen [pO2] ≤ 55 mg HG and/or pulse oxygen [ox]
< 88%), baseline hypercapnia (carbon dioxide [CO2] ≥ 45 mm Hg; there are also
other, less objective criteria, including severe end-organ damage from
diabetes/hypertension, severe atherosclerotic disease (heart, brain, aorta,
peripheral artery)

- Tumor(s) must be in a location/configuration such that risk of fistula is
considered relatively low; this means that there can be no evidence of tumor
invasion of a major (lobar/hilar) pulmonary vessel(s), aorta, vena cava, trachea
or mainstem bronchus or esophagus; additional studies may be needed to assess
this, including CT angiogram, MRI, bronchoscopy, esophagoscopy

- One or more of the following "risk" criteria for failure with conventional SBRT
treatment alone:

- Peripheral tumor ≥ 4 cm in any dimension

- Central tumor (i.e. gross tumor within 2 cm of a major bronchus/vessel, or
heart/pericardium), including hilar lymph node(s)

- Multiple tumors (i.e. satellitosis-defined T3-4, or bilateral synchronous
primary lung cancer; note that the maximum number of total lesions allowable on
this study for treatment with SBRT is 3 (Three), and all lesions must be
amenable to SBRT and treated with SBRT on this study; note that it is not
necessary for all lesions felt to be malignant to be biopsied

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

- Hemoglobin ≥ 9.0 g/dl

- Absolute neutrophil count ≥ 1,500/mcL

- Platelet count ≥ 100,000 cells/mcL

- Total bilirubin ≤ 1.5 X institutional upper limit of normal

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) ≤
2.5 X institutional upper limit of normal

- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X
institutional upper limit of normal

- Serum creatinine ≤ 1.5 X institutional upper limit of normal

- Alkaline phosphatase ≤ 2.5 X institutional upper limit of normal, unless bone
metastasis is present in the absence of liver metastasis

- Women of child-bearing potential and men must agree to use adequate contraception
(double barrier method of birth control or abstinence) 6 weeks prior to study entry,
for the duration of study participation and for 6 months after completing treatment;
should a woman become pregnant or suspect that she is pregnant while she or her
partner is participating in this study, she should inform the treating physician
immediately

- Subjects must have the ability to understand and the willingness to sign a written
informed consent document

- Patients must not have grade 2 or greater pre-existing peripheral neuropathy (per
Common Terminology Criteria for Adverse Events [CTCAE] 4.0)

Exclusion Criteria:

- Prior treatment toxicities (i.e. any toxicity from treatment of a previous cancer )
must be resolved to ≤ grade 1 according to National Cancer Institute (NCI) CTCAE
version 4.0 (except alopecia)

- Patients who are receiving any other investigational agents

- Patients with prior invasive malignancy within two years of enrollment are excluded

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Abraxane (paclitaxel albumin-stabilized nanoparticle formulation) or
other agents used in this study

- Patients with severe cardiac disease including symptomatic congestive heart failure,
unstable angina, or have experience an acute myocardial infarction within the past 6
months; please note: patients with chronic obstructive pulmonary disease (COPD) are
not excluded

- Pregnant or breastfeeding women are excluded from this study; breastfeeding should be
discontinued

- Known human immunodeficiency virus (HIV)-positive patients are ineligible