MnSOD (Esophageal Protectant) to Prevent Esophagitis During Radiation/Chemotherapy Treatment for Non-Small Cell Lung Cancer (NSCLC)

This is a Phase I-II study evaluating the feasibility, safety, and efficacy of swallowed
MnSOD plasmid/liposome (PL) transgene given as protection against radiation-induced
esophagitis during concurrent paclitaxel and carboplatin chemotherapy with thoracic radiation
in subjects with locally advanced non-small cell lung cancer (NSCLC). Phase I of the study
will assess the feasibility and safety of MnSOD PL by dose escalation in 3 cohorts of 3
chemoradiotherapy subjects each (Cohort1 = 0.3 mg/dose, Cohort2 = 3 mg/dose, Cohort3 = 30
mg/dose). The highest dose completed (as determined by toxicity monitoring for 8 weeks from
initial treatment) will be the starting dose for Phase II. Phase II will examine the efficacy
of MnSOD PL by assessing the incidence of Grade 3 or 4 esophagitis in 27 additional
chemoradiotherapy subjects. Incidence of esophageal toxicity, as well as clinical response to
the combination of chemoradiotherapy with MnSOD PL are the outcomes of interest.

Inclusion Criteria:

- Histologically or cytologically documented NSCLC including squamous cell carcinoma,
adenocarcinoma (including bronchoalveolar cell), and large cell anaplastic carcinoma
(including giant and clear cell carcinomas) and poorly differentiated non-small cell
lung cancer. Totally resected tumors are excluded.

- Subjects must be without evidence of M0.

- Subjects with T1 or T2 disease with N2 or tumor stage 3, lymph node metastasis 1-2 (
stage 1) disease (Stage IIIA) are eligible if they are medically inoperable. Subjects
with T4 with any N or any T with N3 disease are eligible. Radiographic evidence of
mediastinal lymph nodes >2.0 cm in the largest diameter is sufficient to stage N2 or
N3 disease. If the largest mediastinal node is < 2.0 cm in diameter and this is the
basis for stage III disease, then at least one of the nodes must be proven positive
cytologically or histologically.

- Subjects with tumors adjacent to a vertebral body are eligible as long as all gross
disease can be encompassed in the radiation boost field. The boost volume must be
limited to < 50% of the ipsilateral lung volume.

- Subjects with a pleural effusion that is a transudate, cytologically negative and
non-bloody are eligible if the radiation oncologists feel the tumor can still be
encompassed within a reasonable field of radiotherapy. Exudative, bloody, or
cytologically malignant effusions are ineligible. If a pleural effusion can be seen on
the chest CT but not on chest X-ray and is too small to tap, the subject will be
eligible.

- Subjects must be deemed a suitable candidate for protocol treatment by both Radiation
Oncology and Medical Oncology

- Subjects must have a Performance Status > 70 (Karnofsky Performance Scale).

- Subjects Weight loss < 10% in 3 months prior to diagnosis.

- Subjects must be male or female > 18 years.

- Subjects must have had no prior systemic chemotherapy, radiation therapy to the
thorax, or total surgical resection.

- At least 3 weeks since formal exploratory thoracotomy and the subject has recovered
from surgery, or 1 week from diagnostic thoracoscopy.

- Laboratory values must be as follows: (See Section 6.1 of the full protocol for
required timing): Granulocytes > 2,000/ml, Platelets > 100,000/ml, Hemoglobin* > 8
mg/dl, Bilirubin < 1.5 x normal, Creatinine clearance > 50 ml/n (24 hour or
calculated, forced expiratory volume at one second > 800 cc. Note: *Physician can
maintain a subject's hemoglobin with the use of Erythropoetin or transfusions
prophylactic use of G-CSF (colony stimulating factor, is not permitted).

- Subjects must have a MRI or CT brain scan within 4 weeks prior to study entry to rule
out asymptomatic brain metastases.

- Subjects must be informed of the investigational nature of the study and sign an
informed consent form and have no serious medical or psychiatric illnesses that would
prevent informed consent.

- No history of serious cardiac disease that is not adequately controlled.

- Female subjects must be non-pregnant and non-lactating. Female subjects of
childbearing potential must implement an effective method of contraception during the
study. All women of childbearing potential must have a pre-study negative serum or
urine pregnancy test within 7 days prior to study entry.

Exclusion Criteria

- Inability to meet any of the above eligibility requirements