Clinical trial NCT02390063: Vaccination in Prostate Cancer (VANCE)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2015-03-17
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Vaccine safety and immunogenicity
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Cellular and humoral immune response with CHAMVA
timeFrame: Up to 52 weeks
measure: Cellular and humoral immune response with MVA
timeFrame: Up to 52 weeks
measure: PSA level change secondary to vaccination
timeFrame: Participants will be followed for the duration of the study, up to 52 weeks
measure: MRI or Gleason score change secondary to vaccination
timeFrame: Participants will be followed for the duration of the study, up to 52 weeks
measure: Regulatory T-cell response
timeFrame: Participants will be followed for the duration of the study, up to 52 weeks
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: University of Oxford
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Oxford University Hospitals NHS Trust
name: Freddie Hamdy
role: STUDY_CHAIR
References:
citation: 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):e000928. doi: 10.1136/jitc-2020-000928.