<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03815942</url>
  </required_header>
  <id_info>
    <org_study_id>ADVANCE</org_study_id>
    <nct_id>NCT03815942</nct_id>
  </id_info>
  <brief_title>VAccination in Early and ADvanced Prostate caNCEr</brief_title>
  <acronym>ADVANCE</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Vaccitech (UK) Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Oxford</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a clinical trial of a new treatment for prostate cancer that is a type of vaccine&#xD;
      that could be a new way to treat cancer. A vaccine that could alert the immune system to the&#xD;
      presence of cancer cells in the body may enable the immune system to target and kill those&#xD;
      cells effectively. This vaccine is intended to work by making the immune system kill cells&#xD;
      that have a special protein (called 5T4) that is present on the surface of cancer cells. The&#xD;
      vaccine is made up of two recombinant viruses (&quot;ChAdOx1&quot;- chimpanzee adenovirus Ox1 and &quot;MVA&quot;&#xD;
      - modified vaccinia Ankara) that have been designed to produce the 5T4 protein and have been&#xD;
      modified so that they are weakened and cannot reproduce themselves within the body like&#xD;
      normal viruses. Once injected into the body, these viruses make the 5T4 protein and help the&#xD;
      body's immune system to learn to target this protein and destroy cancer cells.&#xD;
&#xD;
      This vaccine will be used in combination with the immunotherapy drug called nivolumab which&#xD;
      is an anti-PD-1 (Programmed Death protein-1) monoclonal antibody. This is a molecule that&#xD;
      releases the brakes on the immune system and helps the immune system to kill cancer cells&#xD;
      more efficiently. Nivolumab as a monotherapy was approved for treatment of several tumour&#xD;
      types but not for the prostate cancer.&#xD;
&#xD;
      This study will evaluate the safety and efficacy of ChAdOx1-MVA 5T4 vaccine in combination&#xD;
      with nivolumab in low and intermediate risk prostate cancer patients who have elected to have&#xD;
      their prostate removed and in patients with advanced metastatic prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">December 10, 2018</start_date>
  <completion_date type="Anticipated">July 10, 2021</completion_date>
  <primary_completion_date type="Anticipated">March 10, 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety - incidence of treatment-related adverse events.</measure>
    <time_frame>From baseline to 12 months</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy - measure composite response rate defined as one of the following: 1) change in circulating tumour DNA, 2) change in serum PSA</measure>
    <time_frame>From baseline to 12 months</time_frame>
    <description>Number of participants with 50% or more change in ctDNA or PSA concentration in the blood from baseline to 12 months post treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate immune responses to the vaccine antigen in the periphery</measure>
    <time_frame>From baseline to 12 months</time_frame>
    <description>Number of participants with peripheral 5T4-specific T cell responses secondary to treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate immune cell subsets in the prostate secondary to treatment (for surgical cohort)</measure>
    <time_frame>From baseline to radical prostatectomy, an expected average of 6 weeks</time_frame>
    <description>Number of participants with intraprostatic infiltration of CD3+CD8+ T cells secondary to treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate progression-free survival following study treatment (for advanced metastatic cancer cohort)</measure>
    <time_frame>6-12 months</time_frame>
    <description>Number of participants experiencing progression-free survival at 6 and 12 months post treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate overall survival following study treatment (for advanced metastatic cancer cohort)</measure>
    <time_frame>6-12 months</time_frame>
    <description>Number of participants experiencing overall survival at 6 and 12 months post treatment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Intermediate Risk Prostate Cancer</condition>
  <condition>Castration-resistant Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Intermediate risk prostate cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Advanced metastatic prostate cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ChAdOx1-MVA 5T4 vaccine</intervention_name>
    <description>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</description>
    <arm_group_label>Advanced metastatic prostate cancer</arm_group_label>
    <arm_group_label>Intermediate risk prostate cancer</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab Infusion [Opdivo]</intervention_name>
    <description>Nivolumab is to be administered as a flat dose of 480 mg over approximately 60-minutes via IV infusion</description>
    <arm_group_label>Advanced metastatic prostate cancer</arm_group_label>
    <arm_group_label>Intermediate risk prostate cancer</arm_group_label>
    <other_name>anti-PD-1 monoclonal antibody</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For all participants:&#xD;
&#xD;
          -  Histologically confirmed adenocarcinoma of the prostate cancer&#xD;
&#xD;
          -  Any antineoplastic therapy must have been completed a minimum of 28 days prior to&#xD;
             enrolment&#xD;
&#xD;
          -  Systemic antimicrobial therapy must have been completed a minimum of 7 days prior to&#xD;
             enrolment&#xD;
&#xD;
          -  An archival specimen of tumour tissue should be available&#xD;
&#xD;
          -  Baseline laboratory parameters must meet the following criteria:&#xD;
&#xD;
        Haemoglobin ≥ 80 g/L, White cell count ≥ 2.0 x10^9/L, Neutrophils ≥ 1.5 x10^9/L,&#xD;
        Lymphocytes ≥ 0.5 x10^9/L, Platelets ≥ 100 x10^9/L, Creatinine Clearance ≥ 40 ml/min by&#xD;
        Cockcroft Gault formulation, Total Bilirubin ≤ 1.5 ULN, Alanine Aminotransferase ≤ 1.5 ULN,&#xD;
        Amylase ≤ 1.5 ULN&#xD;
&#xD;
        For surgical cohort:&#xD;
&#xD;
          -  Clinically localised or locally advanced disease deemed operable by the treating&#xD;
             consultant urological surgeon i.e.: Gleason score ≤ 7, local tumour stage ≤T3c and&#xD;
             deemed operable, no evidence of metastases (Nx/N0 and Mx/M0), no evidence of high&#xD;
             grade Gleason 5 disease, PSA ≤ 20 ng/ml&#xD;
&#xD;
          -  Scheduled for and considered fit for radical prostatectomy&#xD;
&#xD;
        For advanced metastatic cohort:&#xD;
&#xD;
          -  Evidence of at least one distant metastasis based on MRI, CT, PET or bone scintigraphy&#xD;
&#xD;
          -  Established on and suitable to continue with androgen deprivation therapy (ADT) using&#xD;
             any luteinizing hormone releasing hormone (LHRH) agonist&#xD;
&#xD;
          -  On treatment with anti-androgen therapy using either abiraterone (Zytiga®) or&#xD;
             enzalutamide (Xtandi®) and demonstrating evidence of disease progression at the time&#xD;
             of enrolment&#xD;
&#xD;
          -  Suitable to continue therapy with either abiraterone or enzalutamide at the time of&#xD;
             enrolment at discretion of their managing clinician&#xD;
&#xD;
          -  Patients who have received chemotherapy following progression on androgen-targeting&#xD;
             therapies are eligible&#xD;
&#xD;
          -  Satisfactory functional status defined as ECOG Performance Status ≤ 1&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        For all participants:&#xD;
&#xD;
          -  Any prior diagnosis or clinical suspicion of autoimmune disease&#xD;
&#xD;
          -  History of allergic disease or reaction likely to be exacerbated by any component of&#xD;
             the vaccine, e.g. egg products&#xD;
&#xD;
          -  Other prior malignancy with an estimated ≥ 30% chance of relapse within 2 years&#xD;
&#xD;
          -  Participation in another research study involving an investigational product or&#xD;
             investigational surgical procedure in the 30 days preceding enrolment, or planned use&#xD;
             during the study period&#xD;
&#xD;
          -  Any prior exposure to checkpoint inhibitor drugs including anti-PD-1, anti-PD-L1, or&#xD;
             anti-CTLA-4 monoclonal antibodies or any prior treatment with investigational vaccines&#xD;
&#xD;
          -  Administration of immunoglobulins and/or any blood products within the one month&#xD;
             preceding the planned administration of the study drugs&#xD;
&#xD;
          -  Seropositive for hepatitis B surface antigen (HBsAg)&#xD;
&#xD;
          -  Seropositive for hepatitis C virus (antibodies to HCV)&#xD;
&#xD;
          -  Any confirmed or suspected immunocompromised state&#xD;
&#xD;
          -  Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema&#xD;
&#xD;
          -  History of anaphylaxis in relation to vaccination or any clinically significant&#xD;
             allergic disease likely to be exacerbated by any component of the vaccine or&#xD;
             checkpoint inhibitor preparations&#xD;
&#xD;
        For advanced metastatic cohort:&#xD;
&#xD;
          -  The treating oncologist estimates a subject's life expectancy to be ≤ 6 months&#xD;
&#xD;
          -  Any active, previously treated, or suspected intracranial or leptomeningeal metastases&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adrian VS Hill</last_name>
    <role>Study Chair</role>
    <affiliation>University of Oxford</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Oncology, The Christie NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer and Haematology Centre, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Oxford</city>
        <zip>OX3 7LE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>November 27, 2020</last_update_submitted>
  <last_update_submitted_qc>November 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03815942
org study id: ADVANCE
nct id: NCT03815942
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety - incidence of treatment-related adverse events.
time frame: From baseline to 12 months
description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
measure: 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
description: Number of participants with 50% or more change in ctDNA or PSA concentration in the blood from baseline to 12 months post treatment
measure: Evaluate immune responses to the vaccine antigen in the periphery
time frame: From baseline to 12 months
description: Number of participants with peripheral 5T4-specific T cell responses secondary to treatment
measure: 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
description: Number of participants with intraprostatic infiltration of CD3+CD8+ T cells secondary to treatment
measure: Evaluate progression-free survival following study treatment (for advanced metastatic cancer cohort)
time frame: 6-12 months
description: Number of participants experiencing progression-free survival at 6 and 12 months post treatment
measure: Evaluate overall survival following study treatment (for advanced metastatic cancer cohort)
time frame: 6-12 months
description: Number of participants experiencing overall survival at 6 and 12 months post treatment
arm group label: Intermediate risk prostate cancer
arm group type: Experimental
description: 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.
arm group label: Advanced metastatic prostate cancer
arm group type: Experimental
description: 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.
intervention type: Biological
intervention name: ChAdOx1-MVA 5T4 vaccine
description: 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
arm group label: Advanced metastatic prostate cancer
arm group label: Intermediate risk prostate cancer
intervention type: Drug
intervention name: Nivolumab Infusion [Opdivo]
description: Nivolumab is to be administered as a flat dose of 480 mg over approximately 60-minutes via IV infusion
arm group label: Advanced metastatic prostate cancer
arm group label: Intermediate risk prostate cancer
other name: anti-PD-1 monoclonal antibody
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Adrian VS Hill
role: Study Chair
affiliation: University of Oxford
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Nivolumab
sharing ipd: Undecided