Vaccination in Prostate Cancer (VANCE)

NCT02390063 | Completed Phase 1 DMC

• 1 other identifier: VANCE01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Vaccine safety and immunogenicity

  Development or increase in anti-5T4 cellular and humoral responses in patients treated with CHAMVA or CHAMVA + CTX

  Up to 52 weeks

Secondary Outcomes (5)

• 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

Study Arms (8)

CHAMVA standard regime

EXPERIMENTAL

ChAdOx1.5T4 prime followed by two boost of MVA.5T4 vaccine at 4 week intervals until radical prostatectomy

Biological: ChAdOx1.5T4; Biological: MVA.5T4

CHAMVA+CTX standard regime

EXPERIMENTAL

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.

Biological: ChAdOx1.5T4; Biological: MVA.5T4; Drug: Cyclophosphamide

MVA standard regime

ACTIVE COMPARATOR

Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy

Biological: MVA.5T4

MVA+CTX standard regime

ACTIVE COMPARATOR

One week of low dose cyclophosphamide pre-conditioning before each vaccination.Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy

Biological: MVA.5T4; Drug: Cyclophosphamide

CHAMVA accelerated regime

EXPERIMENTAL

ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy.

Biological: ChAdOx1.5T4; Biological: MVA.5T4

CHAMVA+CTX accelerated regime

EXPERIMENTAL

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.

Biological: ChAdOx1.5T4; Biological: MVA.5T4; Drug: Cyclophosphamide

CHAMVA accelerated regime AS

EXPERIMENTAL

ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance.

Biological: ChAdOx1.5T4; Biological: MVA.5T4

CHAMVA+CTX accelerated regime AS

EXPERIMENTAL

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.

Biological: ChAdOx1.5T4; Biological: MVA.5T4; Drug: Cyclophosphamide

Interventions

ChAdOx1.5T4 BIOLOGICAL

A recombinant simian adenovirus encoding human tumour-associated antigen 5T4

CHAMVA accelerated regime; CHAMVA accelerated regime AS; CHAMVA standard regime; CHAMVA+CTX accelerated regime; CHAMVA+CTX accelerated regime AS; CHAMVA+CTX standard regime

MVA.5T4 BIOLOGICAL

A recombinant replication deficient Modified Vaccinia Ankara virus encoding human tumour-associated antigen 5T4

CHAMVA accelerated regime; CHAMVA accelerated regime AS; CHAMVA standard regime; CHAMVA+CTX accelerated regime; CHAMVA+CTX accelerated regime AS; CHAMVA+CTX standard regime; MVA standard regime; MVA+CTX standard regime

Cyclophosphamide DRUG

Metronomic cyclophosphamide (50mg bd)

Also known as: CTX, CY, Cytoxan

CHAMVA+CTX accelerated regime; CHAMVA+CTX accelerated regime AS; CHAMVA+CTX standard regime; MVA+CTX standard regime

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Males aged 18 and older
• Histologically confirmed prostate cancer diagnosed on biopsy within 6 months

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (2)

University of Oxford

Oxford, OX3 7DQ, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2IF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32591433 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

TroVax; Cyclophosphamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Freddie Hamdy

  Oxford University Hospitals NHS Trust

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2015
• First Posted: March 17, 2015
• Study Start: June 1, 2015
• Primary Completion: May 15, 2018
• Study Completion: May 15, 2019
• Last Updated: February 10, 2020

Record last verified: 2018-05

Locations

GB (2)