Cisplatin and Nab-paclitaxel for (N2) Defined NSCLC

Objectives

To estimate the rate of N2 nodal clearance at time of surgery in patients with NSCLC
undergoing treatment with neoadjuvant nab-paclitaxel plus cisplatin and surgery.

Estimate response rate and complete response rate in non-small cell lung cancer (NSCLC)
after 3 cycles of neoadjuvant nab-paclitaxel plus cisplatin

Estimate complete pathological response of primary tumor and lymph nodes at the time of
surgery in patients with NSCLC undergoing treatment with neoadjuvant nab-paclitaxel plus
cisplatin

Estimate disease free survival for all patients who undergo surgery and also stratified by
nodal clearance

Patients will be assigned to receive three (3) cycles of cisplatin (mg/m2) and
nab-paclitaxel (125 mg/m2). Surgery will then be conducted per standard of care.

Approximately 4-12 weeks after the surgical resection, patients will receive one of three
available treatment regimens based on the results of the surgical reports, which include:
Two four week cycles of therapy of Cisplatin and Nab-paclitaxel; Four three-week cycles of
Cisplatin and Pemetrexed, or four three-week cycles of Cisplatin and Gemcitabine

Thirty (30) days after treatment ends, subjects will be followed for any ongoing serious
adverse events, if necessary, and every 3-6 months thereafter for two years.

After the two years of follow-up, subjects will be followed for survival and disease status

Estimate overall survival for entire group and stratified by nodal clearance

To estimate event free survival (EFS)

Estimate time to distant recurrence and time to local recurrence following total study
procedures

Inclusion Criteria:

- 18 years of age; no upper age limit

- Diagnosis of NSCLC, histologically or cytologically confirmed

- Pathologic mediastinal staging to include endobronchial ultrasound with or without
endoscopic ultrasound (EBUS =/- EUS) including evaluation of N3 nodes

- Systemic staging including CT that covers the chest, liver and adrenal glands or a
PET/CT; MRI of the brain is required and must be negative for metastatic spread. If a
patient is unable to tolerate MRI or has a contraindication to MRI, a head CT scan
with and without contrast is acceptable

- International Association for the Study of Lung Cancer (IASLC) version 7, subset of
stage IIIA single station (N2) disease; specifically T1a-T3, N2(+) with no invasion
of key structures (e.g., chest wall or diaphragm)

- Surgically resectable disease, and patient deemed an appropriate surgical candidate
by a thoracic surgeon prior to enrollment

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Adequate organ and bone marrow function as defined by:

Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3; Hemoglobin ≥ 10g/dL (it is acceptable
to reach this through transfusion); Platelets > 100,000 cells/mm3; Creatinine clearance ≥
60 mg/dL (Cockcroft-Gault equation); Total bilirubin ≤ 1.5 mg/dL; Alkaline phosphatase ≤
2.5 x upper limit of normal (ULN); Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x ULN;
Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN;

- Women of childbearing potential and sexually active men must agree to use effective
contraception prior to study entry, for the duration of study participation and for
three months after completing treatment. Adequate contraception is defined as any
medically recommended method (or combination of methods) per standard of care

- Negative serum or urine Human Chorionic Gonadotropin(b-hCG) pregnancy test within 14
days of D1 of neoadjuvant chemotherapy for women of childbearing potential

- Informed consent obtained and signed

Exclusion Criteria:

- Forced expiratory volume (FEV) ≤ 1.2 L/s

- T3 tumor defined by invasion of key structures (only T3 defined by size > 7cm
allowed)

- Any lymph code > 3 cm or multistation N2 lympadenopathy

- Patient better served by concurrent chemoradiotherapy: The protocol recognizes that
institutional standards regarding which patients are best served by operative and
nonoperative approaches vary. Therefore, consistent with the American College of
Chest Physicians (ACCP) guidelines, the protocol recommends multidisciplinary
discussion of each patient and enrollment only of patients felt best serviced by the
approach described herein

- ≥ Grade 2 pre-existing peripheral neuropathy (per CTCAEv4)

- Prior history of hypersensitivity to taxane or platinum therapy. If either agent was
previously administered, the patient must have tolerated it well and have recovered
from any adverse events

- Recurrent disease or second primary lung cancer (only de novo IIIA disease allowed)

- Other active, invasive malignancy requiring ongoing therapy or expected to require
systemic therapy within two years; localized squamous cell carcinoma of the skin,
basal-cell carcinoma of the skin, carcinoma in-situ of the cervix, or other
malignancies requiring locally ablative therapy only will not result in exclusion.

- Prior treatment of any kind for this malignancy

- Have received treatment with any drug that has not received regulatory approval for
that indication within the 30 days prior to study entry

- Any serious, uncontrolled medical disorder that would impair the ability of the
subject to receive protocol driven therapy