- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03815942
VAccination in Early and ADvanced Prostate caNCEr (ADVANCE)
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
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.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Manchester, United Kingdom, M20 4BX
- Department of Oncology, The Christie NHS Foundation Trust
-
Oxford, United Kingdom, OX3 7LE
- Cancer and Haematology Centre, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Intermediate risk prostate cancer
ChAdOx1.5T4 on week 0 followed by booster injection of MVA.5T4 and nivolumab infusion on week 1.
Patients will undergo radical prostatectomy on week 6.
|
ChAdOx1.5T4 will be administered intramuscularly in an extremity (e.g.
thigh) at a dose of 2.5 x10^10 virus particles followed by MVA.5T4 administered via the same route at the dose of 2x10^8 plaque forming units
Nivolumab is to be administered as a flat dose of 480 mg over approximately 60-minutes via IV infusion
Other Names:
|
EXPERIMENTAL: Advanced metastatic prostate cancer
ChAdOx1.5T4 on week 0 followed by booster injections of MVA.5T4 on week 4, ChAdOx1.5T4 on week 12 and MVA.5T4 on week 16.
Nivolumab infusions are to be administered on week 4, 8 and 12.
|
ChAdOx1.5T4 will be administered intramuscularly in an extremity (e.g.
thigh) at a dose of 2.5 x10^10 virus particles followed by MVA.5T4 administered via the same route at the dose of 2x10^8 plaque forming units
Nivolumab is to be administered as a flat dose of 480 mg over approximately 60-minutes via IV infusion
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety - incidence of treatment-related adverse events.
Time Frame: From baseline to 12 months
|
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
|
From baseline to 12 months
|
Efficacy - measure composite response rate defined as one of the following: 1) change in circulating tumour DNA, 2) change in serum PSA
Time Frame: From baseline to 12 months
|
Number of participants with 50% or more change in ctDNA or PSA concentration in the blood from baseline to 12 months post treatment
|
From baseline to 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluate immune responses to the vaccine antigen in the periphery
Time Frame: From baseline to 12 months
|
Number of participants with peripheral 5T4-specific T cell responses secondary to treatment
|
From baseline to 12 months
|
Evaluate immune cell subsets in the prostate secondary to treatment (for surgical cohort)
Time Frame: From baseline to radical prostatectomy, an expected average of 6 weeks
|
Number of participants with intraprostatic infiltration of CD3+CD8+ T cells secondary to treatment
|
From baseline to radical prostatectomy, an expected average of 6 weeks
|
Evaluate progression-free survival following study treatment (for advanced metastatic cancer cohort)
Time Frame: 6-12 months
|
Number of participants experiencing progression-free survival at 6 and 12 months post treatment
|
6-12 months
|
Evaluate overall survival following study treatment (for advanced metastatic cancer cohort)
Time Frame: 6-12 months
|
Number of participants experiencing overall survival at 6 and 12 months post treatment
|
6-12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Adrian VS Hill, University of Oxford
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ADVANCE
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Castration-resistant Prostate Cancer
-
Nuvation Bio Inc.WithdrawnProstate Cancer | Prostate Neoplasm | Cancer of the Prostate | Prostatic Cancer | Castrate Resistant Prostate Cancer | Cancer of Prostate | Castration Resistant Prostatic Cancer | Castration Resistant Prostatic NeoplasmsUnited States
-
Janux TherapeuticsRecruitingProstate Cancer | Metastatic Castration-resistant Prostate Cancer | Castration Resistant Prostatic CancerUnited States, Australia
-
Universität des SaarlandesRecruitingProstate Cancer Metastatic | Advanced Prostate Carcinoma | Castration Resistant Prostatic CancerGermany
-
Myovant Sciences GmbHRecruitingMetastatic Castration-Resistant Prostate Cancer | Metastatic Castration-Sensitive Prostate Cancer | Non-Metastatic Castration-Resistant Prostate CancerUnited States
-
Astellas Pharma IncPfizerCompletedCastration-resistant Prostate CancerJapan
-
University Hospital, GrenobleTerminatedCastration-resistant Prostate CancerFrance
-
Massachusetts General HospitalBayerCompletedProstate Cancer | Castration-resistant Prostate Cancer | Castration-resistant Prostate Cancer Metastatic to BoneUnited States
-
Sidney Kimmel Comprehensive Cancer Center at Johns...Clarus TherapeuticsRecruitingProstate Cancer | Castration-resistant Prostate Cancer | Metastatic Castration-resistant Prostate CancerUnited States
-
BAMF HealthRecruitingMetastatic Castration-resistant Prostate CancerUnited States
-
Translational Research Center for Medical Innovation...CompletedCastration Resistant Prostate Cancer (CRPC)
Clinical Trials on ChAdOx1-MVA 5T4 vaccine
-
Vaccitech (UK) LimitedRecruiting
-
Barinthus BiotherapeuticsCompletedHPV Infection | CIN1Belgium, United Kingdom, Estonia
-
University of OxfordCompletedSeasonal InfluenzaUnited Kingdom
-
Cancer Research UKVaccitech (UK) LimitedRecruitingNon-small Cell Lung Cancer (NSCLC)United Kingdom
-
CanSino Biologics Inc.Recruiting
-
The Methodist Hospital Research InstituteOxford BioMedicaTerminatedProstatic NeoplasmsUnited States
-
Federal University of Espirito SantoInstituto René Rachou/FiocruzRecruiting
-
Assiut UniversityActive, not recruitingChAdOx1 nCoV-19 VaccineEgypt
-
Korea University Guro HospitalAjou University School of Medicine; Korean Center for Disease Control and Prevention and other collaboratorsRecruitingInflammation | Vaccine Adverse Reaction | Vaccine Immune Response | COVID-19 VaccinationKorea, Republic of
-
University of OxfordActive, not recruiting