<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/NCT03284268</url>
  </required_header>
  <id_info>
    <org_study_id>FSJD-RTB-2015</org_study_id>
    <nct_id>NCT03284268</nct_id>
  </id_info>
  <brief_title>Evaluate Safety and the Oncolitic Adenovirus VCN-01 Activity in Patients With Refractory Retinoblastoma</brief_title>
  <acronym>RTB</acronym>
  <official_title>Phase I Study, Single Site, Open Label With Dose Escalation, for Evaluate Safety and the Oncolitic Adenovirus VCN-01 Activity in Patients With Refractory Retinoblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundació Sant Joan de Déu</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundació Sant Joan de Déu</source>
  <oversight_info>
    <has_dmc>No</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>
      Phase I study, single site, open label with dose escalation, for evaluate safety and the&#xD;
      oncolitic Adenovirus VCN-01 activity in patients with refractory retinoblastoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 6, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>180 days</time_frame>
    <description>The safety and tolerability of two intravitreal injections of VCN-01 will be determined with dose escalation until the maximum tolerated dose (MTD) is established based on the evaluation of adverse events and the observation of any dose-limiting toxicity (TLD).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor response</measure>
    <time_frame>28 days</time_frame>
    <description>Tumor response rate (ORR) to VCN-01 at 28 days post-administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VCN-01</measure>
    <time_frame>180 days</time_frame>
    <description>Virus presence in blood samples, aqueous humor, ocular surface and nasal swabs, and its difference between the viral particles before and after the treatment to evaluate the excretion profile of the CNV-01.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune response</measure>
    <time_frame>180 days</time_frame>
    <description>The presence of neutralizing antibodies in blood samples in study patients to assess the immune response.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Histopathology of enucleated eyes after treatment with VCN-01</measure>
    <time_frame>180 days</time_frame>
    <description>Presence of VCN-01 in vitreous humor samples of enucleated eyes</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">13</enrollment>
  <condition>Retinoblastoma, Recurrent</condition>
  <arm_group>
    <arm_group_label>Dose escalation of VCN-01</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose lower : 2E+9 viral particules/eye Dose medium: 2E+10 viral particules/eye Dose high: 2E+11 viral particules/eye</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>VCN-01</intervention_name>
    <description>VCN-01 intravitreal injection</description>
    <arm_group_label>Dose escalation of VCN-01</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with retinoblastoma with a somatic mutation of the geneRB1 and active tumor&#xD;
             in a single eye, or germinal mutation of RB1 with active tumor/s in an eye and the&#xD;
             contralateral eye unaffected, enucleated or without tumor activity. In both cases,&#xD;
             relapsed or refractory with the use of systemic, intraarterial or intravitreal&#xD;
             chemotherapy or radiotherapy, in accordance with the availability at his/her referral&#xD;
             site, in whom enucleation is the only recommended treatment under opinion of the&#xD;
             medical team treating the case at the originating referral site.&#xD;
&#xD;
          2. Normal renal function: serum creatinine: &lt;45μmol/L (0-2 years); &lt;57μmol/L (3-6 years);&#xD;
             &lt;60μmol/L (7-10 years); &lt;80μmol/L (11-13 years).&#xD;
&#xD;
          3. Normal Hepatic function: serum ALT: &lt;0,52μkat/L (de 9 months -12 years); serum AST:&#xD;
             61-80 g/L (8 months - 5 years); 63-83 g/L (5-9 years); 63-82 g/L (9-12 years).&#xD;
&#xD;
          4. Adequate marrow reserve manifested in an absolute neutrophil count&gt; 1000 / mm3,&#xD;
             platelets&gt; 100,000 / mm3 and hemoglobin&gt; 8 g / dl, without transfusional or cytokine&#xD;
             support at least one month prior to study entry.&#xD;
&#xD;
          5. Age greater than one year and less than 12 years at the time of inclusion in the&#xD;
             study.&#xD;
&#xD;
          6. Informed consent form signed.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of factors that require immediate enucleation of the affected eye such as&#xD;
             glaucoma, rubeosis iridis, anterior chamber involvement.&#xD;
&#xD;
          2. Comorbidities: Uncontrolled epilepsy with anticonvulsant treatment, cardiac disease&#xD;
             not compensated by treatment.&#xD;
&#xD;
          3. Active Infections.&#xD;
&#xD;
          4. Other chronic or active acute diseases that under the criterion of the researcher were&#xD;
             an exclusion criterion.&#xD;
&#xD;
          5. History of having received attenuated or live vaccines in the 30 days prior to&#xD;
             inclusion in the study.&#xD;
&#xD;
          6. Any cause of Immunosuppression.&#xD;
&#xD;
          7. Trilateral Retinoblastoma.&#xD;
&#xD;
          8. Extraocular spread.&#xD;
&#xD;
          9. History of having received treatment for retinoblastoma with chemotherapy or radiation&#xD;
             therapy by any means within 30 days prior to inclusion in the study.&#xD;
&#xD;
         10. Patients who can not complete the study procedures for reasons psychological or&#xD;
             social.&#xD;
&#xD;
         11. Pregnancy. Female patients with procreative potential should be agree to undergo a&#xD;
             blood or urine pregnancy test and the result should be negative to enter the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jaume Catalá Mora, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Sant Joan de Deu</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jaume Catalá Mora, Dr.</last_name>
    <phone>932 53 21 00</phone>
    <email>jcatalam@sjdhospitalbarcelona.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Guillermo Chantada, Dr</last_name>
    <phone>932 53 21 00</phone>
    <email>gchantada@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hospital Sant Joan de Déu</name>
      <address>
        <city>Barcelona</city>
        <zip>08950</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jaume Catalá Mora, Dr</last_name>
      <phone>932 53 21 00</phone>
    </contact>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 15, 2017</study_first_posted>
  <last_update_submitted>June 7, 2022</last_update_submitted>
  <last_update_submitted_qc>June 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gene therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Retinoblastoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Anonymized individual data of participants will be shared with Authorities at the end of the Clinical development plan by the CTD (Common Technical Document). Results will be published in a scientific publication</ipd_description>
  </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/NCT03284268
org study id: FSJD-RTB-2015
nct id: NCT03284268
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Phase I study, single site, open label with dose escalation, for evaluate safety and the
      oncolitic Adenovirus VCN-01 activity in patients with refractory retinoblastoma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events
time frame: 180 days
description: The safety and tolerability of two intravitreal injections of VCN-01 will be determined with dose escalation until the maximum tolerated dose (MTD) is established based on the evaluation of adverse events and the observation of any dose-limiting toxicity (TLD).
measure: Tumor response
time frame: 28 days
description: Tumor response rate (ORR) to VCN-01 at 28 days post-administration.
measure: VCN-01
time frame: 180 days
description: Virus presence in blood samples, aqueous humor, ocular surface and nasal swabs, and its difference between the viral particles before and after the treatment to evaluate the excretion profile of the CNV-01.
measure: Immune response
time frame: 180 days
description: The presence of neutralizing antibodies in blood samples in study patients to assess the immune response.
measure: Histopathology of enucleated eyes after treatment with VCN-01
time frame: 180 days
description: Presence of VCN-01 in vitreous humor samples of enucleated eyes
arm group label: Dose escalation of VCN-01
arm group type: Experimental
description: Dose lower : 2E+9 viral particules/eye Dose medium: 2E+10 viral particules/eye Dose high: 2E+11 viral particules/eye
intervention type: Genetic
intervention name: VCN-01
description: VCN-01 intravitreal injection
arm group label: Dose escalation of VCN-01
criteria: 
gender: All
minimum age: 1 Year
maximum age: 12 Years
healthy volunteers: No
last name: Jaume Catalá Mora, Dr
role: Principal Investigator
affiliation: Hospital Sant Joan de Deu
last name: Jaume Catalá Mora, Dr.
phone: 932 53 21 00
email: jcatalam@sjdhospitalbarcelona.org
last name: Guillermo Chantada, Dr
phone: 932 53 21 00
email: gchantada@yahoo.com
facility: 
status: Recruiting
contact: 
country: Spain
responsible party type: Sponsor
mesh term: Retinoblastoma
sharing ipd: No
ipd description: Anonymized individual data of participants will be shared with Authorities at the end of the Clinical development plan by the CTD (Common Technical Document). Results will be published in a scientific publication