Immunization of Patients With Non Small Cell Lung Cancer (NSCLC)
Immunization of Patients With Non Small Cell Lung Cancer (NSCLC)
The study of the vaccine will proceed in two stages after the method of Simon (102). In the
 first stage, 15 patients will be accrued and treated. If two or fewer objective immunologic
 responses occur, the study will be terminated. If 3 or more responses are observed, the study
 will proceed to the second stage, accruing an additional 22 patients. If the second stage is
 complete and a total of 9 or more immunologic responses are observed among the 37 patients
 treated, the treatment response rate for the vaccine will be considered high enough to
 warrant further study. Conversely, if the evaluation of the vaccine concludes at the first
 stage, or if 8 or fewer total immunologic responses occur after completing the second stage,
 the vaccine will not be considered for further study.
This is an uncontrolled, non-randomized trial to evaluate safety, immunogenicity and
 feasibility of a new vaccine, consisting of semi-allogeneic fibroblasts transfected with
 autologous tumor-derived DNA. Briefly, the plan is to use a two-stage trial design and to
 initially enroll 15 patients with non small cell lung cancer (NSCLC) over a period of 2
 years. The patients will undergo surgery and a portion of the primary tumor specimen not
 necessary for the pathologic diagnosis will be obtained to serve as a source of tumor DNA.
 Each DNA-based vaccine will contain 1 x 10e7 DNA-transfected human allogeneic fibroblasts.
 The vaccine will be lethally irradiated before it is used for immunization. It will be
 administered intradermally in the Outpatient Clinic. Patients delayed-type hypersensitivity
 (DTH) responses will be tested but will not be an eligibility criterion. Immunologic response
 to the vaccine will be evaluated. If there is no evidence of toxicity, and >3 of the 15
 initial patients show immunologic response, the second stage of the study will be opened for
 accrual of 22 patients. All patients will be monitored by IFN-g secretion in ELISPOT assays
 prior to and after vaccination for the frequency of T-cells responsive to autologous tumor
 (if available) and/or to the vaccine. The patients will also be evaluated before and after
 vaccination for the capability of their T cells to respond to activating signals delivered
 via the T cell receptor (TcR).
Inclusion Criteria:

 -  Written informed consent conforming to the institutional guidelines obtained from the
 patient.

 -  A diagnosis of non-small cell lung cancer (NSCLC), subjects will undergo or have had
 surgical resection.

 -  Age 18 or above.

 -  Karnofsky performance status > 70

 -  Adequate hematologic function:

 -  Absolute neutrophil count > 1,000/mm3

 -  Absolute lymphocyte count > 1,000/mm3

 -  Hemoglobin > 9 g/dL

 -  Platelets > 100,000/mm3

 -  Liver function tests:

 -  Bilirubin (total) < 1.7 mg/dL

 -  Alkaline phosphatase < 252 u/L

 -  SGOT < 108 u/L

 -  Kidney profile:

 -  Serum electrolytes

 -  Sodium 136-146 mEq/L

 -  Potassium 3.5-5.0 mEq/L

 -  Bicarbonate 21-31 mEq/L

 -  Chloride 98-107 mmol/L

 -  Serum creatinine < 3 x ULN

 -  BUN 8-26 mg/dL

 -  At least a 12 week interval should have elapsed between vaccination and any prior
 radiation therapy, chemotherapy or any other treatment. Patients should have recovered
 from surgery and adjuvant treatment.

 Exclusion Criteria:

 Subjects will be EXCLUDED from participation in the study if any of the following apply:

 -  One or more of the Inclusion Criteria are not met.

 -  A significant history or current evidence of cardiac disease including, but not
 limited to: congestive heart failure, coronary artery disease, angina pectoris,
 uncontrolled hypertension, serious arrythmias or myocardial infarction within the
 previous six months.

 -  Evidence of active infection requiring antibiotic therapy.

 -  Active intracranial metastases. Patients with previously resected intracranial disease
 and/or previously irradiated intracranial metastases that have been stable for four
 weeks are eligible.

 -  Pregnant or lactating women. Pregnant women are excluded from this study. Women of
 childbearing potential must have a negative pregnancy test. Because there is an
 unknown but potential risk for adverse events in nursing infants secondary to
 treatment of the mother, breastfeeding should be discontinued if the mother is treated
 on study.

 -  Patients requiring systemic corticosteroids (unless patient has had NO STEROIDS IN THE
 PAST 4 WEEKS).

 -  Autoimmune disease including, but not limited to, rheumatoid arthritis, systemic lupus
 erythematous, multiple sclerosis, or ankylosing spondylitis

 -  Patient must not have post-obstructive pneumonia or other serious infection at the
 time of registration or other serious underlying medical condition that would impair
 the ability of the patient to receive protocol treatment.

 -  Subject is not a candidate for complete resection of the carcinoma via pneumonectomy,
 lobectomy, bilobectomy, extended wedge resection or anatomic segmentectomy with or
 without sleeve resection as noted in the surgical plan..

 -  Prior resection of lung cancer is allowed, if at least five years have elapsed between
 previous resection and registration.

 -  No prior malignancy is allowed except for adequately treated basal cell or squamous
 cell skin cancer, in situ cervical cancer, or other cancer from which the patient has
 been disease-free for at least 5 years prior to registration.

 -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
 arrhythmia, or psychiatric illness/social situations that would limit compliance with
 study requirements.