Safety Study of DNA Vaccine Delivered by Intradermal Electroporation to Treat Colorectal Cancer

NCT ID: NCT01064375

Last Updated: 2022-08-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2016-08-31

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CEA DNA prime (cohort I)

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.

Group Type: EXPERIMENTAL

tetwtCEA DNA (wt CEA with tetanus toxoid Th epitope)

Intervention Type: BIOLOGICAL

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

Derma Vax (electroporation device)

Intervention Type: DEVICE

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

Cyclophosphamide

Intervention Type: DRUG

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

CEA DNA boost (cohort II)

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.

Group Type: EXPERIMENTAL

tetwtCEA DNA (wt CEA with tetanus toxoid Th epitope)

Intervention Type: BIOLOGICAL

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

Derma Vax (electroporation device)

Intervention Type: DEVICE

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

Cyclophosphamide

Intervention Type: DRUG

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

CEA DNA prime + GM-CSF (cohort III)

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.

Group Type: EXPERIMENTAL

tetwtCEA DNA (wt CEA with tetanus toxoid Th epitope)

Intervention Type: BIOLOGICAL

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

Derma Vax (electroporation device)

Intervention Type: DEVICE

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

GM-CSF

Intervention Type: BIOLOGICAL

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

Cyclophosphamide

Intervention Type: DRUG

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

Interventions

tetwtCEA DNA (wt CEA with tetanus toxoid Th epitope)

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

Intervention Type: BIOLOGICAL

Derma Vax (electroporation device)

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

Intervention Type: DEVICE

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

Intervention Type: BIOLOGICAL

Cyclophosphamide

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

Intervention Type: DRUG

Other Intervention Names

GM-CSF; cyclophosphamide; GM-CSF; cyclophosphamide; cyclophosphamide; Sendoxan

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska Institutet

OTHER

Sponsor Role: collaborator

Swedish Institute for Infectious Disease Control

OTHER

Sponsor Role: collaborator

Cyto Pulse Sciences, Inc.

INDUSTRY

Sponsor Role: collaborator

Maria Liljefors

OTHER

Sponsor Role: lead

Responsible Party

Maria Liljefors

MD, senior consultant

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Maria Liljefors, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Oncology, Karolinska University Hospital/Institute

Locations

Department of Oncology, Karolinska University Hospital

Stockholm, , Sweden

Countries

Sweden

Other Identifiers

2009-009863-75

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

El-porCEA

Identifier Type: -

Identifier Source: org_study_id