Low- and intermediate-risk prostate cancer and advanced metastatic prostate cancer MedDRA version: 20.0 Level: PT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10066489 Term: Progression of prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 2
Conditions
Interventions
Product Name: ChAdOx1.5T4
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: ChAdOx1.5T4
Other descriptive name: ChAdOx1 virus encoding 5T4 antigen
Concentration unit: U/ml unit(s)/mil
Sponsors
University of Oxford
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Low- or intermediate-risk prostate cancer group: - Males aged over 18 years - Histologically confirmed adenocarcinoma of the prostate - 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 - Absence of any indication to perform urgent surgery that would not allow completion of the study interventions prior to radical prostatectomy Metastatic prostate cancer groups: - Males aged over 18 years - Histologically confirmed adenocarcinoma of the prostate cancer. Note, any Gleason grade or primary tumour staging at diagnosis is permitted. - 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. LHRH agonist therapy may include goserelin (Zoladex®), leuprorelin acetate (Prostap®) or any other licenced product in this class. - On treatment with anti-androgen therapy using either abiraterone (Zytiga®) or enzalutamide (Xtandi®) and demonstrating evidence of disease progression at the time of enrolment, defined according Prostate Cancer Working Group 2 Criteria as either: • increasing PSA or; • progressive nodal or visceral disease or; • progressive bone metastases - Suitable to continue therapy with either abiraterone or enzalutamide at the time of enrolment - Satisfactory functional status defined as Eastern Cooperative Oncology Group (ECOG) Performance Status = 1 Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: All participants: The patient may not enter the study if any of the following apply: - Any prior diagnosis or clinical suspicion of autoimmune disease including, but not limited to, systemic lupus erythematosus, inflammatory bowel disease, vasculitis, Grave’s disease and type I diabetes mellitus. Note, subjects with known pre-existing clinically silent positive autoantibodies should not be included. - Any diagnosis of a non-prostate malignancy within the last 3 years where in the opinion of the investigator the risk of recurrence exceeds 30% - 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 - History of allergic disease or reaction likely to be exacerbated by any component of the vaccine, e.g. egg products - Administration of immunoglobulins and/or any blood products within the one month preceding the planned administration of the study drugs - Seropositive for Hepatitis B (HBV) Hepatitis C virus (HCV), human immunodeficiency virus (HIV) - Any confirmed or suspected immunocompromised state, including but not limited to, asplenia, a history of atypical, recurrent or severe infections, or, regular use (> 14 days) of systemic immunosuppressant medication within the past 6 months. - 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, as listed in the Investigator’s Brochure and SmPC - Confirmed or suspected recreational drug use or harmful drinking in the last 5 years - History of a serious psychiatric condition or other circumstances that may be associated with impaired mental capacity - Other prior malignancy with an estimated = 30% chance of relapse within 2 years. Allowed recent cancers include (but are not limited to) non-melanomatous skin cancer and superficial bladder cancer - Evidence of significant clinical disorder or laboratory finding which in the opinion of the investigating physician increases the level of risk to the patient, limits the ability of the patient to participate in the study or impairs interpretation of the study data Exclusion Criteria – Metastatic prostate cancer groups The volunteer may not enter the metastatic prostate cancer arm of the study if: - The treating oncologist or urological cancer MDT estimates a subject’s life expectancy to be = 6 months - Any active, previously treated, or suspected intracranial or leptomeningeal metastases
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and efficacy of ChAd-MVA 5T4 vaccination in combination with checkpoint inhibitor nivolumab when administered to early stage and advanced metastatic prostate cancer patients.;Secondary Objective: 1) To assess the magnitude of immune responses generated by ChAd-MVA vaccination in combination with nivolumab. 2) To investigate whether ChAd-MVA vaccination in combination with nivolumab will lead to a change in the composition of immune cell subsets in the prostate. 3) To investigate whether ChAd-MVA vaccinations in combination with nivolumab will impact on prostate cancer progression and overall survival. ;Primary end point(s): 1. Actively and passively collected data on adverse events up to 12 months from enrolment 2. Serum PSA kinetics secondary to study treatment as measured by rate of change (low- and intermediate-risk prostate cancer patients) 3. Reduction of serum PSA and circulating tumor DNA following study treatment (metastatic prostate cancer patients);Timepoint(s) of evaluation of this end point: 1. Throughout the study, from baseline to last study visit/assessment 2. From baseline to surgery 3. Throughout the study, from baseline to last study visit/assessment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Development or increase of vaccine-specidfic immune response 2. Immune cell subsets in the prostate pre and post study treatment (low- and intermediate-risk prostate cancer patients) 3. Radiographic progression-free survival (metastatic prostate cancer patients) 4. Overall survival (metastatic prostate cancer patients);Timepoint(s) of evaluation of this end point: 1. Throughout the study, from baseline to last study visit/assessment 2. 2. From baseline to surgery 3. At 6 and 12 months after enrolment 4. At 6 and 12 months after enrolment | — |
Countries
Switzerland, United Kingdom
Contacts
Public ContactDr Irina Redchenko
The Jenner Institute, University of Oxford
Outcome results
None listed