Clinical trial NCT03815942: VAccination in Early and ADvanced Prostate caNCEr
Official title: Phase I/II Open Label Non-randomised Safety and Efficacy Study of the Viral Vectored ChAd-MVA 5T4 Vaccine in Combination With PD-1 Checkpoint Blockade in Low- or Intermediate-risk Localized or Locally Advanced Prostate Cancer and Advanced Metastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Intermediate Risk Prostate Cancer
Castration-resistant Prostate Cancer
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Barinthus Biotherapeutics
First posted: 2019-01-24
Enrollment: 23
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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"- chimpanzee adenovirus Ox1 and "MVA" - modified vaccinia Ankara) 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 vaccine will be used in combination with the immunotherapy drug called nivolumab which is an anti-PD-1 (Programmed Death protein-1) monoclonal antibody. This is a molecule that releases the brakes on the immune system and helps the immune system to kill cancer cells more efficiently. Nivolumab as a monotherapy was approved for treatment of several tumour types but not for the prostate cancer.

This study will evaluate the safety and efficacy of ChAdOx1-MVA 5T4 vaccine in combination with nivolumab in low and intermediate risk prostate cancer patients who have elected to have their prostate removed and in patients with advanced metastatic prostate cancer.


Eligibility criteria: Inclusion Criteria:

For all participants:

* Histologically confirmed adenocarcinoma of the prostate cancer
* Any antineoplastic therapy must have been completed a minimum of 28 days prior to enrolment
* Systemic antimicrobial therapy must have been completed a minimum of 7 days prior to enrolment
* An archival specimen of tumour tissue should be available
* Baseline laboratory parameters must meet the following criteria:

Haemoglobin ≥ 80 g/L, White cell count ≥ 2.0 x10\^9/L, Neutrophils ≥ 1.5 x10\^9/L, Lymphocytes ≥ 0.5 x10\^9/L, Platelets ≥ 100 x10\^9/L, Creatinine Clearance ≥ 40 ml/min by Cockcroft Gault formulation, Total Bilirubin ≤ 1.5 ULN, Alanine Aminotransferase ≤ 1.5 ULN, Amylase ≤ 1.5 ULN

For surgical cohort:

* Clinically localised or locally advanced disease deemed operable by the treating consultant urological surgeon i.e.: Gleason score ≤ 7, local tumour stage ≤T3c and deemed operable, no evidence of metastases (Nx/N0 and Mx/M0), no evidence of high grade Gleason 5 disease, PSA ≤ 20 ng/ml
* Scheduled for and considered fit for radical prostatectomy

For advanced metastatic cohort:

* Evidence of at least one distant metastasis based on MRI, CT, PET or bone scintigraphy
* Established on and suitable to continue with androgen deprivation therapy (ADT) using any luteinizing hormone releasing hormone (LHRH) agonist
* On treatment with anti-androgen therapy using either abiraterone (Zytiga®) or enzalutamide (Xtandi®) and demonstrating evidence of disease progression at the time of enrolment
* Suitable to continue therapy with either abiraterone or enzalutamide at the time of enrolment at discretion of their managing clinician
* Patients who have received chemotherapy following progression on androgen-targeting therapies are eligible
* Satisfactory functional status defined as ECOG Performance Status ≤ 1

Exclusion Criteria:

For all participants:

* Any prior diagnosis or clinical suspicion of autoimmune disease
* History of allergic disease or reaction likely to be exacerbated by any component of the vaccine, e.g. egg products
* Other prior malignancy with an estimated ≥ 30% chance of relapse within 2 years
* Participation in another research study involving an investigational product or investigational surgical procedure in the 30 days preceding enrolment, or planned use during the study period
* Any prior exposure to checkpoint inhibitor drugs including anti-PD-1, anti-PD-L1, or anti-CTLA-4 monoclonal antibodies or any prior treatment with investigational vaccines
* Administration of immunoglobulins and/or any blood products within the one month preceding the planned administration of the study drugs
* Seropositive for hepatitis B surface antigen (HBsAg)
* Seropositive for hepatitis C virus (antibodies to HCV)
* Any confirmed or suspected immunocompromised state
* Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema
* History of anaphylaxis in relation to vaccination or any clinically significant allergic disease likely to be exacerbated by any component of the vaccine or checkpoint inhibitor preparations

For advanced metastatic cohort:

* The treating oncologist estimates a subject's life expectancy to be ≤ 6 months
* Any active, previously treated, or suspected intracranial or leptomeningeal metastases

Primary outcomes:
measure: Safety - incidence of treatment-related adverse events.
timeFrame: From baseline to 12 months
measure: Efficacy - measure composite response rate defined as one of the following: 1) change in circulating tumour DNA, 2) change in serum PSA
timeFrame: From baseline to 12 months
Secondary outcomes:
measure: Evaluate immune responses to the vaccine antigen in the periphery
timeFrame: From baseline to 12 months
measure: Evaluate immune cell subsets in the prostate secondary to treatment (for surgical cohort)
timeFrame: From baseline to radical prostatectomy, an expected average of 6 weeks
measure: Evaluate progression-free survival following study treatment (for advanced metastatic cancer cohort)
timeFrame: 6-12 months
measure: Evaluate overall survival following study treatment (for advanced metastatic cancer cohort)
timeFrame: 6-12 months
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Department of Oncology, The Christie NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Cancer and Haematology Centre, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust
Study officials:
affiliation: University of Oxford
name: Adrian VS Hill
role: STUDY_CHAIR
References: