Clinical trial NCT01064375: Safety Study of DNA Vaccine Delivered by Intradermal Electroporation to Treat Colorectal Cancer
Official title: Assessment of Safety and Immunogenicity of Intradermal Electroporation of tetwtCEA DNA in Patients With Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Keywords: DNA vaccine
Electroporation
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
name: Swedish Institute for Infectious Disease Control
name: Cyto Pulse Sciences, Inc.
First posted: 2010-02-08
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: To evaluate the safety and immunogenicity of a DNA immunisation approach where tetwtCEA DNA will be administered in combination with electroporation.
timeFrame: Within 72 weeks after immunisation
Secondary outcomes:
measure: 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
timeFrame: Within 72 weeks after immunisation
measure: To compare effects (safety and immunogenicity) of additional adjuvance with GM-CSF
timeFrame: Within 72 weeks after immunsation
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Department of Oncology, Karolinska University Hospital
Study officials:
affiliation: Department of Oncology, Karolinska University Hospital/Institute
name: Maria Liljefors, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: