Safety Study of DNA Vaccine Delivered by Intradermal Electroporation to Treat Colorectal Cancer (El-porCEA)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Karolinska University Hospital.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Karolinska Institutet
Swedish Institute for Infectious Disease Control
Cyto Pulse Sciences, Inc.
Information provided by (Responsible Party):
Maria Liljefors, Karolinska University Hospital
ClinicalTrials.gov Identifier:
NCT01064375
First received: February 5, 2010
Last updated: February 27, 2012
Last verified: February 2012
  Purpose

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.

Condition Intervention Phase
Colorectal Cancer
Biological: tetwtCEA DNA (wt CEA with tetanus toxoid Th epitope)
Device: Derma Vax (electroporation device)
Biological: GM-CSF
Drug: Cyclophosphamide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Assessment of Safety and Immunogenicity of Intradermal Electroporation of tetwtCEA DNA in Patients With Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Karolinska University Hospital:

Primary Outcome Measures:
  • To evaluate the safety and immunogenicity of a DNA immunisation approach where tetwtCEA DNA will be administered in combination with electroporation. [ Time Frame: Within 72 weeks after immunisation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Within 72 weeks after immunisation ] [ Designated as safety issue: No ]
  • To compare effects (safety and immunogenicity) of additional adjuvance with GM-CSF [ Time Frame: Within 72 weeks after immunsation ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: December 2009
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CEA DNA prime (cohort I)
5 patients, tetwtCEA DNA intradermal delivery with electroporation, not previously vaccinated with CEA66 DNA
Biological: tetwtCEA DNA (wt CEA with tetanus toxoid Th epitope)
Two vaccinations at week 0 and 12. Intradermal administration of 400ug DNA/dose with electroporation
Other Names:
  • GM-CSF
  • cyclophosphamide
Device: Derma Vax (electroporation device)
Electrical pulses applied to vaccination sites in skin using Derma Vax immediately after DNA administration
Other Names:
  • GM-CSF
  • cyclophosphamide
Drug: Cyclophosphamide
One intravenous dose of 300 mg/m2 will be given three days before each vaccination with tetwtCEA DNA
Other Name: Sendoxan
Experimental: CEA DNA boost (cohort II)
10 patients, tetwtCEA DNA intradermal delivery with electroporation, previously vaccinated with CEA66 DNA
Biological: tetwtCEA DNA (wt CEA with tetanus toxoid Th epitope)
Two vaccinations at week 0 and 12. Intradermal administration of 400ug DNA/dose with electroporation
Other Names:
  • GM-CSF
  • cyclophosphamide
Device: Derma Vax (electroporation device)
Electrical pulses applied to vaccination sites in skin using Derma Vax immediately after DNA administration
Other Names:
  • GM-CSF
  • cyclophosphamide
Drug: Cyclophosphamide
One intravenous dose of 300 mg/m2 will be given three days before each vaccination with tetwtCEA DNA
Other Name: Sendoxan
Experimental: CEA DNA prime + GM-CSF (cohort III)
5 patients, tetwtCEA DNA intradermal delivery with electroporation + GM-CSF, not previously vaccinated with CEA66 DNA
Biological: tetwtCEA DNA (wt CEA with tetanus toxoid Th epitope)
Two vaccinations at week 0 and 12. Intradermal administration of 400ug DNA/dose with electroporation
Other Names:
  • GM-CSF
  • cyclophosphamide
Device: Derma Vax (electroporation device)
Electrical pulses applied to vaccination sites in skin using Derma Vax immediately after DNA administration
Other Names:
  • GM-CSF
  • cyclophosphamide
Biological: GM-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
Other Names:
  • GM-CSF
  • cyclophosphamide
Drug: Cyclophosphamide
One intravenous dose of 300 mg/m2 will be given three days before each vaccination with tetwtCEA DNA
Other Name: Sendoxan

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01064375

Locations
Sweden
Department of Oncology, Karolinska University Hospital
Stockholm, Sweden, 171 76
Sponsors and Collaborators
Maria Liljefors
Karolinska Institutet
Swedish Institute for Infectious Disease Control
Cyto Pulse Sciences, Inc.
Investigators
Principal Investigator: Maria Liljefors, MD, PhD Department of Oncology, Karolinska University Hospital/Institute
  More Information

No publications provided

Responsible Party: Maria Liljefors, MD, senior consultant, Karolinska University Hospital
ClinicalTrials.gov Identifier: NCT01064375     History of Changes
Other Study ID Numbers: El-porCEA, 2009-009863-75
Study First Received: February 5, 2010
Last Updated: February 27, 2012
Health Authority: Sweden: Regional Ethical Review Board
Sweden: Medical Products Agency

Keywords provided by Karolinska University Hospital:
DNA vaccine
Electroporation

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on October 19, 2014