A Randomized Phase I Study to Determine the Safety and Immunogenicity of ChAd-MVA Vaccination Compared to MVA Alone With and Without Low Dose Cyclophosphamide in Low and Intermediate Risk Localised Prostate Cancer
Overview
- Phase
- Phase 1
- Intervention
- ChAdOx1.5T4
- Conditions
- Prostate Cancer
- Sponsor
- University of Oxford
- Enrollment
- 40
- Locations
- 2
- Primary Endpoint
- Vaccine safety and immunogenicity
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a clinical trial of a new treatment for prostate cancer that is a type of vaccine that could be a new way to treat cancer. A vaccine that could alert the immune system to the presence of cancer cells in the body may enable the immune system to target and kill those cells effectively. This vaccine is intended to work by making the immune system kill cells that have a special protein (called 5T4) that is present on the surface of cancer cells. The vaccine is made up of two recombinant viruses ("ChAdOx1" and "MVA") that have been designed to produce the 5T4 protein and have been modified so that they are weakened and cannot reproduce themselves within the body like normal viruses. Once injected into the body, these viruses make the 5T4 protein and help the body's immune system to learn to target this protein and destroy cancer cells.
This is a first-in-human study to evaluate the safety and immunogenicity of ChAdOx1.5T4-MVA.5T4 vaccination regime. It is evaluated in neo-adjuvant setting in low and intermediate risk localised prostate cancer patients who have either decided to have their prostate removed or are stable on active surveillance.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Diagnosis of any cancer other than prostate cancer within the last 5 years (except basal cell carcinoma)
- •Any suspicion of metastatic cancer
- •Any Gleason grade 5 component in the prostatic biopsies
- •Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period
- •Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
- •Seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) or HIV
- •Any confirmed or suspected immunosuppressive or immunodeficient state, asplenia, recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled/topical steroids are allowed)
- •Platelet count \>400,000/μL; Monocytes \>80,000/μL; Hemoglobin \<11g/dL
- •Known allergy to neomycin
- •History of allergic response to previous vaccinia vaccinations
Arms & Interventions
CHAMVA standard regime
ChAdOx1.5T4 prime followed by two boost of MVA.5T4 vaccine at 4 week intervals until radical prostatectomy
Intervention: ChAdOx1.5T4
CHAMVA standard regime
ChAdOx1.5T4 prime followed by two boost of MVA.5T4 vaccine at 4 week intervals until radical prostatectomy
Intervention: MVA.5T4
CHAMVA+CTX standard regime
One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by two boost of MVA.5T4 at 4 week intervals until radical prostatectomy.
Intervention: ChAdOx1.5T4
CHAMVA+CTX standard regime
One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by two boost of MVA.5T4 at 4 week intervals until radical prostatectomy.
Intervention: MVA.5T4
CHAMVA+CTX standard regime
One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by two boost of MVA.5T4 at 4 week intervals until radical prostatectomy.
Intervention: Cyclophosphamide
MVA standard regime
Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy
Intervention: MVA.5T4
MVA+CTX standard regime
One week of low dose cyclophosphamide pre-conditioning before each vaccination.Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy
Intervention: MVA.5T4
MVA+CTX standard regime
One week of low dose cyclophosphamide pre-conditioning before each vaccination.Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy
Intervention: Cyclophosphamide
CHAMVA accelerated regime
ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy.
Intervention: ChAdOx1.5T4
CHAMVA accelerated regime
ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy.
Intervention: MVA.5T4
CHAMVA+CTX accelerated regime
One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy.
Intervention: ChAdOx1.5T4
CHAMVA+CTX accelerated regime
One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy.
Intervention: MVA.5T4
CHAMVA+CTX accelerated regime
One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy.
Intervention: Cyclophosphamide
CHAMVA accelerated regime AS
ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance.
Intervention: ChAdOx1.5T4
CHAMVA accelerated regime AS
ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance.
Intervention: MVA.5T4
CHAMVA+CTX accelerated regime AS
One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance.
Intervention: ChAdOx1.5T4
CHAMVA+CTX accelerated regime AS
One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance.
Intervention: MVA.5T4
CHAMVA+CTX accelerated regime AS
One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance.
Intervention: Cyclophosphamide
Outcomes
Primary Outcomes
Vaccine safety and immunogenicity
Time Frame: Up to 52 weeks
Development or increase in anti-5T4 cellular and humoral responses in patients treated with CHAMVA or CHAMVA + CTX
Secondary Outcomes
- Cellular and humoral immune response with CHAMVA(Up to 52 weeks)
- Cellular and humoral immune response with MVA(Up to 52 weeks)
- PSA level change secondary to vaccination(Participants will be followed for the duration of the study, up to 52 weeks)
- MRI or Gleason score change secondary to vaccination(Participants will be followed for the duration of the study, up to 52 weeks)
- Regulatory T-cell response(Participants will be followed for the duration of the study, up to 52 weeks)