Safety and Immunogenicity of Recombinant DNA and Adenovirus Expressing L523S Protein in Early Stage Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this trial is to examine the safety and immunogenicity of a therapeutic vaccine regimen with recombinant DNA and adenovirus expressing L523S protein in patients with early stage non-small cell lung cancer. The vaccine regimen will consist of two fixed doses of recombinant DNA (pVAX/L523S) followed by two doses of recombinant adenovirus (Ad/L523S). The trial will evaluate the dose escalation of Ad/L523S through three cohorts of patients.

Detailed Description
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The primary objective of the study is to evaluate the safety of the vaccine regimen administered as two doses of pVAX/L523S and two doses of Ad/L523S. The secondary objectives of the study are: To provide initial evidence as to whether CD8+ and CD4+ T cell responses specific for L523S protein can be elicited by two doses of pVAX/L523S followed by two doses of Ad/L523S To provide initial evidence as to whether antibody responses specific for L523S protein can be elicited by two doses of pVAX/L523S followed by two doses of Ad/L523S To investigate the extent to which dose escalation of Ad/L523S affects the elicited immune response

Official Title
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Phase I Open-Label Dose Escalation Trial Evaluating The Safety And Immunogenicity Of Sequential Administration Of Recombinant DNA And Adenovirus Expressing L523S Protein In Patients With Early Stage Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Biological: Recombinant DNA- pVAX/L523S
* Biological: Recombinant adenovirus- Ad/L523S


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Histologically and surgical confirmed diagnosis and stage of IB, IIA, or IIB non-small cell lung cancer (NSCLC) according to the Revised International System for Staging Lung Cancer Primary surgical resection of lung cancer greater than or equal to 4 weeks and less than or equal to 3 years prior to the Day 0 visit No evidence of disease by standard diagnostic tests Chest X-ray and physical examination showing no active disease Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 WBC count greater than or equal to 3,000 cells/mm3 and ANC greater than or equal to 1,500 cells/mm3 Hemoglobin value greater than or equal to 10.0 g/dL and a platelet count greater than or equal to 125,000 cells/mm3 Adequate renal function (defined as serum creatinine <1.5 times the upper limit of normal for females and males) Normal hepatic function (defined as serum bilirubin <1.5 times the upper limit of normal, AST <2.5 times the upper limit of normal and alkaline phosphatase <1.5 times the upper limit of normal) Ability to understand and willingness to sign an IRB-approved written consent prior to study enrollment Female patients must be greater than or equal to 60 years of age, or greater than or equal to 5 years amenorrhea or surgically sterile Male patients who are capable of fathering a child and whose partners are capable of having a child must agree to use adequate contraception for 6 months after enrollment (for men or women-surgical sterilization; for women-hormonal contraceptives, vaginal ring or IUD) Absolute CD4+ cell count of >200 cells/mm3 EXCLUSION CRITERIA: Received pre- or post-operative radiotherapy Received prior biologic, immunologic, or gene therapy for cancer Received an investigational drug (new chemical entity) within three months of study entry Received antibiotics within 2 weeks of Day 0 visit Received systemic or inhaled corticosteroids or immunosuppressive therapy within 4 weeks of Day 0 visit (Use of topical corticosteroids and/or eye drops containing glucocorticosteroids is acceptable) History of active autoimmune diseases such as, but not limited to, systemic lupus erythematosis, sarcoidosis, rheumatoid arthritis, glomerulonephritis, vasculitis, or inflammatory bowel disease History of bleeding in stools and/or diarrhea within 4 weeks of Day 0 visit History of anaphylaxis or severe allergic reaction to vaccines or unknown allergens Received any commercial vaccine within 2 weeks of Day 0 visit Received a major organ allograft Current or previous diagnosis of paraneoplastic syndrome Evidence of a clinically significant active pulmonary infection, emphysema, FeV1 less than or equal to 50% predicted, DLCO less than or equal to 50% predicted, pulse oximetry less than or equal to 92% at the time of study entry Known to be HIV positive Results of virology screening indicate positive serology for HCV (hepatitis C virus) and/or HBsAG (hepatitis B surface antigen). Positive serology for HBV antibodies is allowed. History of other malignancies at other sites, except effectively treated non-melanoma skin cancers, superficial bladder cancer or carcinoma in situ of the cervix or an effectively treated malignancy that has been in remission for greater than 5 years and is highly likely to have been cured Uncontrolled medical problems (neurological, cardiovascular, gastrointestinal, genitourinary or other illness) considered as unwarranted high risk for investigational new drug treatment Patient is lactating Staging classification of TX or NX or MX Prior adjuvant chemotherapy within 8 weeks prior to the Day 0 visit

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Recombinant DNA- pVAX/L523S|nan|
|Biological: Recombinant adenovirus- Ad/L523S|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |