Colorectal Cancer
Conditions
Keywords
DNA vaccine, Electroporation
Brief summary
The purpose of this study is to evaluate the safety and immunogenicity of a CEA DNA immunisation approach in patients with colorectal cancer. The DNA plasmid, tetwtCEA, encodes wild type human CEA fused to a tetanus toxoid T helper epitope. The vaccine will be delivered using an intradermal electroporation device, Derma Vax (Cyto Pulse Sciences). The following will be assessed: * The efficiency of priming immunological responses to CEA by intradermal administration of CEA DNA in combination with electroporation. * The efficiency of boosting immunological responses to CEA by intradermal administration of CEA DNA in combination with electroporation in subjects already vaccinated with CEA DNA. * GM-CSF will be administered to half of the subjects primed with CEA DNA in combination with electroporation and any possible adjuvant effects of GM-CSF will be evaluated.
Interventions
BIOLOGICALtetwtCEA DNA (wt CEA with tetanus toxoid Th epitope)
Two vaccinations at week 0 and 12. Intradermal administration of 400ug DNA/dose with electroporation
DEVICEDerma Vax (electroporation device)
Electrical pulses applied to vaccination sites in skin using Derma Vax immediately after DNA administration
BIOLOGICALGM-CSF
GM-CSF will be given for 4 consecutive days starting the day before the vaccination as an intradermal/subcutaneous administration of 150 ug of GM-CSF
DRUGCyclophosphamide
One intravenous dose of 300 mg/m2 will be given three days before each vaccination with tetwtCEA DNA
Sponsors
Karolinska Institutet
Swedish Institute for Infectious Disease Control
Cyto Pulse Sciences, Inc.
Maria Liljefors
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological confirmed AJCC stage II or III colorectal cancer * Resection of the primary tumour without evidence of remaining macroscopic disease * Allowable standard chemotherapy or radiotherapy in AJCC stage III completed minimum 2 months prior study entry * Patients recruited from vaccination with CEA66 plasmid DNA must have completed trial at 18 months if immune response is proven or proven to be non-immune responders in two consecutive immunoassays. * Age \>18 years * Karnofsky performance \>80% * Life expectancy of greater than 6 months * Normal organ and marrow function * Normal thyroid function as measured by serum T3, T4 and TSH * Normal echocardiogram regarding arrhythmias (chronic or treated atrial fibrillation allowed) * No concurrent treatment (chemotherapy or biological) may be planned during protocol treatment * Women or men of reproductive potential must agree to use adequate contraception prior to study entry and for up to 3 months after the last injection * Ability to understand and the willingness to sign an informed consent document
Exclusion criteria
* Immunotherapy or systemic corticosteroids within 8 weeks prior to entering the study * Chemotherapy or radiotherapy within 2 months prior to entering the study * Known hypersensitivity to GM-CSF * Previous splenectomy or radiation therapy of the spleen * Pregnancy or nursing * HIV seropositivity * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic intracranial disease, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * History of severe neurological, cardiovascular, renal, hepatic, respiratory, bone marrow dysfunction, organ graft or autoimmune disease (treated or not) * Concomitant medication with an anticoagulant (acetylsalicylic acid and low-molecular weight heparin in prophylactic dose allowed) * Other malignancy, except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years * Cardiac demand pacemakers or surgically implanted defibrillators. * Patients that has any metal implants in the area of the injection, (e.g. shoulder implant in the upper arm or shoulder girdle)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the safety and immunogenicity of a DNA immunisation approach where tetwtCEA DNA will be administered in combination with electroporation. | Within 72 weeks after immunisation |
Secondary
| Measure | Time frame |
|---|---|
| To assess the efficiency of boosting immunological responses to CEA by intradermal administration of tetwtCEA DNA in combination with electroporation in subjects already vaccinated with CEA DNA | Within 72 weeks after immunisation |
| To compare effects (safety and immunogenicity) of additional adjuvance with GM-CSF | Within 72 weeks after immunsation |
Countries
Sweden
Outcome results
None listed