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

Corixa Corporation

Status and phase

Unknown

Phase 1

Conditions

Non-Small Cell Lung Cancer

Treatments

Biological: Recombinant adenovirus- Ad/L523S

Biological: Recombinant DNA- pVAX/L523S

Study type

Interventional

Funder types

Industry

Identifiers

NCT00062907

CCL5001-01

Details and patient eligibility

About

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.

Full description

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

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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