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Vaccination in Prostate Cancer (VANCE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02390063
Recruitment Status : Completed
First Posted : March 17, 2015
Last Update Posted : February 10, 2020
Sponsor:
Information provided by (Responsible Party):
University of Oxford

Tracking Information
First Submitted Date  ICMJE March 10, 2015
First Posted Date  ICMJE March 17, 2015
Last Update Posted Date February 10, 2020
Study Start Date  ICMJE June 2015
Actual Primary Completion Date May 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 16, 2016)
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
Original Primary Outcome Measures  ICMJE
 (submitted: March 16, 2015)
  • Number of participants with adverse events [ Time Frame: Week 24 ]
    Actively and passively collected data on adverse events
  • Degree of immunogenicity [ Time Frame: Week 9 ]
    Development or increase in anti-5T4 cellular and humoral responses in patients treated with CHAMVA and CHAMVA+CTX
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 16, 2016)
  • Cellular and humoral immune response with CHAMVA [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2015)
  • Development or increase in anti-5T4 cellular and humoral responses in patients treated with the CHAMVA vaccination regime [ Time Frame: Week 24 ]
  • Development or increase in anti-5T4 cellular and humoral responses in patients treated with the MVA vaccination regime [ Time Frame: Week 24 ]
  • Change in the frequency of regulatory T cells measured in blood and tumour samples from patients treated with metronomic CTX compared to patients not receiving CTX [ Time Frame: Week 9 ]
  • Increase in the number of tumour-infiltrating lymphocytes in surgical specimens [ Time Frame: Week 12 ]
  • PSA level decrease in patients treated with CHAMVA vaccination [ Time Frame: Week 12 ]
  • PSA level decrease in patients treated with MVA vaccination [ Time Frame: Week 12 ]
  • Reduction of tumour burden or Gleason score [ Time Frame: Week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vaccination in Prostate Cancer (VANCE)
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Biological: ChAdOx1.5T4
    A recombinant simian adenovirus encoding human tumour-associated antigen 5T4
  • Biological: MVA.5T4
    A recombinant replication deficient Modified Vaccinia Ankara virus encoding human tumour-associated antigen 5T4
  • Drug: Cyclophosphamide
    Metronomic cyclophosphamide (50mg bd)
    Other Name: CTX, CY, Cytoxan
Study Arms  ICMJE
  • Experimental: CHAMVA standard regime
    ChAdOx1.5T4 prime followed by two boost of MVA.5T4 vaccine at 4 week intervals until radical prostatectomy
    Interventions:
    • Biological: ChAdOx1.5T4
    • Biological: MVA.5T4
  • Experimental: 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.
    Interventions:
    • Biological: ChAdOx1.5T4
    • Biological: MVA.5T4
    • Drug: Cyclophosphamide
  • Active Comparator: MVA standard regime
    Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy
    Intervention: Biological: MVA.5T4
  • Active Comparator: 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
    Interventions:
    • Biological: MVA.5T4
    • Drug: Cyclophosphamide
  • Experimental: CHAMVA accelerated regime
    ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy.
    Interventions:
    • Biological: ChAdOx1.5T4
    • Biological: MVA.5T4
  • Experimental: 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.
    Interventions:
    • Biological: ChAdOx1.5T4
    • Biological: MVA.5T4
    • Drug: Cyclophosphamide
  • Experimental: CHAMVA accelerated regime AS
    ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance.
    Interventions:
    • Biological: ChAdOx1.5T4
    • Biological: MVA.5T4
  • Experimental: 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.
    Interventions:
    • Biological: ChAdOx1.5T4
    • Biological: MVA.5T4
    • Drug: Cyclophosphamide
Publications * Cappuccini F, Bryant R, Pollock E, Carter L, Verrill C, Hollidge J, Poulton I, Baker M, Mitton C, Baines A, Meier A, Schmidt G, Harrop R, Protheroe A, MacPherson R, Kennish S, Morgan S, Vigano S, Romero PJ, Evans T, Catto J, Hamdy F, Hill AVS, Redchenko I. Safety and immunogenicity of novel 5T4 viral vectored vaccination regimens in early stage prostate cancer: a phase I clinical trial. J Immunother Cancer. 2020 Jun;8(1). pii: e000928. doi: 10.1136/jitc-2020-000928.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 13, 2018)
40
Original Estimated Enrollment  ICMJE
 (submitted: March 16, 2015)
32
Actual Study Completion Date  ICMJE May 15, 2019
Actual Primary Completion Date May 15, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria(Radical Prostatectomy patients):

  • Males aged 18 years and older
  • Histologically confirmed prostate cancer diagnosed on biopsy within 6 months
  • Clinically localised, low or intermediate risk prostate cancer, i.e.:

    • Gleason score ≤ 7
    • Local tumour stage ≤T2c
    • No evidence of metastases (Nx/N0 and Mx/M0)
    • PSA ≤ 20 ng/ml
  • Scheduled for and considered fit for radical prostatectomy
  • Absence of any indication to perform urgent surgery that would not allow administration of the vaccine during the 12 week period prior to radical prostatectomy
  • No invasive treatment for prostatic disease within the last 2 years
  • Subject is free of clinically apparent/active autoimmune disease (no prior confirmed diagnosis or treatment for autoimmune disease including Systemic Lupus Erythematosis, Grave's Disease, Hashimoto's Thyroiditis, Multiple Sclerosis, and Insulin Dependent Diabetes Mellitus). Note subjects with Non-Insulin Dependent Diabetes Mellitus can be included.
  • Subject has adequate bone marrow function as defined by an Absolute Lymphocyte Count (ALC) ≥ 500/µL, Absolute Neutrophil Count (ANC) >1200/µL, Platelet Count >100,000/µL.
  • Subject must practice a reliable form of contraception (barrier or vasectomy) while they are being treated with vaccines and another effective method of birth control must also be used by their partner

Inclusion Criteria (Active Surveillance patients)

  • Males aged 18 and older
  • Histologically confirmed prostate cancer diagnosed on biopsy within 6 months
  • Clinically localised, low or intermediate risk prostate cancer, i.e.:

    • Gleason score ≤ 7
    • Local tumour stage ≤T2c
    • No evidence of metastases (Nx/N0 and Mx/M0)
    • PSA ≤ 20 ng/ml
  • Stable disease on Active Surveillance for a minimum of 12 months previously
  • Suitable to remain on Active Surveillance at time of last clinical assessment
  • No invasive treatment for prostatic disease within the last 2 years
  • Subject is free of clinically apparent/active autoimmune disease (no prior confirmed diagnosis or treatment for autoimmune disease including Systemic Lupus Erythematosis, Grave's Disease, Hashimoto's Thyroiditis, Multiple Sclerosis, and Insulin Dependent Diabetes Mellitus). Note subjects with Non-Insulin Dependent Diabetes Mellitus can be included.
  • Subject has adequate bone marrow function as defined by an Absolute Lymphocyte Count (ALC) ≥ 500/µL, Absolute Neutrophil Count (ANC) >1200/µL, Platelet Count >100,000/µL.
  • Subject must practice a reliable form of contraception (barrier or vasectomy) while they are being treated with vaccines and another effective method of birth control must also be used by their partner

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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02390063
Other Study ID Numbers  ICMJE VANCE01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Oxford
Study Sponsor  ICMJE University of Oxford
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Freddie Hamdy Oxford University Hospitals NHS Trust
PRS Account University of Oxford
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP