NCT01064375

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_1 colorectal-cancer

Timeline
Completed

Started Dec 2009

Longer than P75 for phase_1 colorectal-cancer

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2009

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

February 5, 2010

Completed
3 days until next milestone

First Posted

Study publicly available on registry

February 8, 2010

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2012

Completed
4.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2016

Completed
Last Updated

August 19, 2022

Status Verified

August 1, 2022

Enrollment Period

2.2 years

First QC Date

February 5, 2010

Last Update Submit

August 18, 2022

Conditions

Keywords

DNA vaccineElectroporation

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • 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

Study Arms (3)

CEA DNA prime (cohort I)

EXPERIMENTAL

5 patients, tetwtCEA DNA intradermal delivery with electroporation, not previously vaccinated with CEA66 DNA. Electrical pulses applied to vaccination sites in skin using Derma Vax immediately after DNA administration. One dose of Cyclophosphamide (300 mg/m2) will be given i.v. three days before each vaccination with tetwtCEA DNA.

Biological: tetwtCEA DNA (wt CEA with tetanus toxoid Th epitope)Device: Derma Vax (electroporation device)Drug: Cyclophosphamide

CEA DNA boost (cohort II)

EXPERIMENTAL

10 patients, tetwtCEA DNA intradermal delivery with electroporation, previously vaccinated with CEA66 DNA.Electrical pulses applied to vaccination sites in skin using Derma Vax immediately after DNA administration.One dose of Cyclophosphamide (300 mg/m2) will be given i.v. three days before each vaccination with tetwtCEA DNA.

Biological: tetwtCEA DNA (wt CEA with tetanus toxoid Th epitope)Device: Derma Vax (electroporation device)Drug: Cyclophosphamide

CEA DNA prime + GM-CSF (cohort III)

EXPERIMENTAL

5 patients, tetwtCEA DNA intradermal delivery with electroporation + GM-CSF, not previously vaccinated with CEA66 DNA.Electrical pulses applied to vaccination sites in skin using Derma Vax immediately after DNA administration.One dose of Cyclophosphamide (300 mg/m2) will be given i.v. three days before each vaccination with tetwtCEA DNA.

Biological: tetwtCEA DNA (wt CEA with tetanus toxoid Th epitope)Device: Derma Vax (electroporation device)Biological: GM-CSFDrug: Cyclophosphamide

Interventions

Two vaccinations at week 0 and 12. Intradermal administration of 400ug DNA/dose with electroporation

Also known as: GM-CSF, cyclophosphamide
CEA DNA boost (cohort II)CEA DNA prime (cohort I)CEA DNA prime + GM-CSF (cohort III)

Electrical pulses applied to vaccination sites in skin using Derma Vax immediately after DNA administration

Also known as: GM-CSF, cyclophosphamide
CEA DNA boost (cohort II)CEA DNA prime (cohort I)CEA DNA prime + GM-CSF (cohort III)
GM-CSFBIOLOGICAL

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

Also known as: cyclophosphamide
CEA DNA prime + GM-CSF (cohort III)

One intravenous dose of 300 mg/m2 will be given three days before each vaccination with tetwtCEA DNA

Also known as: Sendoxan
CEA DNA boost (cohort II)CEA DNA prime (cohort I)CEA DNA prime + GM-CSF (cohort III)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Oncology, Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Granulocyte-Macrophage Colony-Stimulating FactorCyclophosphamide

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological FactorsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Maria Liljefors, MD, PhD

    Department of Oncology, Karolinska University Hospital/Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD, senior consultant

Study Record Dates

First Submitted

February 5, 2010

First Posted

February 8, 2010

Study Start

December 1, 2009

Primary Completion

March 1, 2012

Study Completion

August 1, 2016

Last Updated

August 19, 2022

Record last verified: 2022-08

Locations