Vaccination in Prostate Cancer (VANCE)
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT02390063
- Lead Sponsor
- University of Oxford
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 40
Not provided
- 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
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
- History of hypersensitivity and haemorrhagic cystitis
- Any history of anaphylaxis
- Suspected or known current injecting drug or alcohol abuse (as defined by an alcohol intake of greater than 42 units per week)
- History of a serious psychiatric condition or other circumstance s that may be associated with not understanding or complying with the study protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description CHAMVA standard regime MVA.5T4 ChAdOx1.5T4 prime followed by two boost of MVA.5T4 vaccine at 4 week intervals until radical prostatectomy MVA standard regime MVA.5T4 Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy CHAMVA+CTX standard regime MVA.5T4 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. CHAMVA accelerated regime AS MVA.5T4 ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance. CHAMVA accelerated regime MVA.5T4 ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy. CHAMVA standard regime ChAdOx1.5T4 ChAdOx1.5T4 prime followed by two boost of MVA.5T4 vaccine at 4 week intervals until radical prostatectomy CHAMVA+CTX standard regime ChAdOx1.5T4 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. CHAMVA accelerated regime ChAdOx1.5T4 ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy. CHAMVA+CTX accelerated regime ChAdOx1.5T4 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. CHAMVA+CTX accelerated regime MVA.5T4 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. CHAMVA+CTX accelerated regime Cyclophosphamide 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. MVA+CTX standard regime MVA.5T4 One week of low dose cyclophosphamide pre-conditioning before each vaccination.Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy CHAMVA accelerated regime AS ChAdOx1.5T4 ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance. CHAMVA+CTX accelerated regime AS ChAdOx1.5T4 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. CHAMVA+CTX accelerated regime AS MVA.5T4 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. CHAMVA+CTX standard regime Cyclophosphamide 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. MVA+CTX standard regime Cyclophosphamide One week of low dose cyclophosphamide pre-conditioning before each vaccination.Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy CHAMVA+CTX accelerated regime AS Cyclophosphamide 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.
- Primary Outcome Measures
Name Time Method Vaccine safety and immunogenicity Up to 52 weeks Development or increase in anti-5T4 cellular and humoral responses in patients treated with CHAMVA or CHAMVA + CTX
- Secondary Outcome Measures
Name Time Method Cellular and humoral immune response with CHAMVA Up to 52 weeks Development or increase in anti-5T4 cellular and humoral responses in patients treated with the CHAMVA vaccination regimes
Cellular and humoral immune response with MVA Up to 52 weeks Development or increase in anti-5T4 cellular and humoral response in patients treated with the MVA vaccination regimes.
PSA level change secondary to vaccination Participants will be followed for the duration of the study, up to 52 weeks PSA level decrease in patients treated with CHAMVA or MVA vaccination at week 4,8 or 12.
MRI or Gleason score change secondary to vaccination Participants will be followed for the duration of the study, up to 52 weeks Reduction of tumour burden or Gleason score at weeks 4, 8 or 12.
Regulatory T-cell response Participants will be followed for the duration of the study, up to 52 weeks Change in the frequency of regulatory T-cells measured in blood or tumour samples from patients treated with metronomic cyclophosphamide compared to patients not receiving cyclophosphamide
Trial Locations
- Locations (2)
University of Oxford
🇬🇧Oxford, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom