<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/NCT02998983</url>
  </required_header>
  <id_info>
    <org_study_id>AR-RACO-2-16</org_study_id>
    <nct_id>NCT02998983</nct_id>
  </id_info>
  <brief_title>Racotumomab in Patients With High-risk Neuroblastoma</brief_title>
  <official_title>Open-label, Multicenter, Phase II Immunotherapy Study With Racotumomab in Patients With High-risk Neuroblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laboratorio Elea Phoenix S.A.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Laboratorio Elea Phoenix S.A.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This clinical trial will be carried out in children diagnosed with high-risk neuroblastoma&#xD;
      that have achieved a complete or very good partial response after standard therapy. An&#xD;
      additional cohort of children who could not achieve these response criteria or that relapsed&#xD;
      after standard therapy but do not have progressive disease will receive Racotumomab together&#xD;
      with metronomic chemotherapy.&#xD;
&#xD;
      The main objectives of this study are to determine the immune response after one-year&#xD;
      duration immunization with Racotumomab, to describe the response of Racotumomab therapy in&#xD;
      minimal residual disease (MRD) in bone marrow and to describe the toxicity profile of&#xD;
      Racotumomab.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Neuroblastoma is the most common extra-cranial tumor in childhood but prognosis is still&#xD;
      poor, even with the advances in its treatment.&#xD;
&#xD;
      New therapeutic strategies have been examined, and several immunotherapeutic approaches,&#xD;
      including combined therapy with monoclonal antibodies (anti-GD2), intravenous interleukin-2&#xD;
      (Il-2) and intravenous granulocyte-macrophage colony-stimulating factor (GM-CSF), and&#xD;
      anti-idiotype vaccines are currently being assessed.&#xD;
&#xD;
      Racotumomab is an anti-idiotype antibody capable of inducing anti-N-glycolyl GM3 antibodies&#xD;
      in patients with neuroblastoma.&#xD;
&#xD;
      The expression of the ganglioside N-glycolyl GM3 was shown in neuroblastoma and this&#xD;
      expression could be useful as a specific target for immunotherapy.&#xD;
&#xD;
      Ractoumomab will be administered once standard therapy for neuroblastoma has been completed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Actual">November 2022</completion_date>
  <primary_completion_date type="Actual">November 2022</primary_completion_date>
  <phase>Phase 2</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>Number of participants who elicit an immune response to a one-year immunization schedule of racotumomab in a cohort study of patients with high-risk neuroblastoma.</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants in whom minimally disseminated disease in the bone marrow decreases or disappears with a one-year immunization schedule of racotumomab compared to baseline values at study entry.</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Related Adverse Events as assessed by CTCAE v4.0 after a one-year immunization schedule of racotumomab when administered alone or together with onco-specific metronomic chemotherapy therapy.</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pattern of expression of N-Glycolyl-GM3 gangliosides in tumor samples obtained at disease diagnosis and during follow up if available.</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">39</enrollment>
  <condition>Neuroblastoma</condition>
  <arm_group>
    <arm_group_label>Racotumomab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dosage form: intradermal injection. Dosage: 0.4 mg. Frequency: the first 5 doses: biweekly injections; the following 10 doses: monthly injections. Duration: 12 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Racotumomab</intervention_name>
    <arm_group_label>Racotumomab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Informed Consent or written child assent, if applicable, prior to any specific&#xD;
             procedure of the study.&#xD;
&#xD;
          2. Aged ≥ 1 year old and ≤ 12 years old at the time of diagnose.&#xD;
&#xD;
          3. High-risk neuroblastoma diagnose according to the International Neuroblastoma Risk&#xD;
             Group Staging System (INRGSS) (Annex I).&#xD;
&#xD;
          4. Patients who have received complete chemotherapy, radiotherapy (if applicable) and&#xD;
             autologous hematopoietic stem cell transplantation (if applicable) not earlier than 30&#xD;
             days prior to being included in the study, and patients of Group I who have completed&#xD;
             therapy with cis retinoic acid or other maintenance onco-specific therapy using the&#xD;
             standard dose for neuroblastoma treatment. .&#xD;
&#xD;
          5. Use of concomitant metronomic chemotherapy by patients of Group II is considered&#xD;
             acceptable.&#xD;
&#xD;
          6. For patients belonging to other risk group who have relapsed or progressed, the period&#xD;
             between the beginning of chemotherapy for the treatment of high-risk neuroblastoma and&#xD;
             the inclusion of patients must not exceed 12 months.&#xD;
&#xD;
          7. Partial or complete remission status, very good partial remission or stable disease&#xD;
             (pursuant to the International Neuroblastoma Response Criteria) at the time of&#xD;
             inclusion (Annex IV).&#xD;
&#xD;
          8. Assessment of the disease must be conducted within 30 days prior to inclusion.&#xD;
&#xD;
          9. Additional studies supporting the response to treatment at the time of inclusion are&#xD;
             required.&#xD;
&#xD;
         10. Normal organ functions according to the following parameters:&#xD;
&#xD;
               -  Adequate cardiac function as defined below:&#xD;
&#xD;
               -  Electrocardiogram (ECG) 30 days prior to inclusion without substantial anomalies.&#xD;
&#xD;
               -  Electrocardiogram (ECG) 30 days prior to inclusion with fractional shortening&#xD;
                  ≥27%&#xD;
&#xD;
               -  Adequate bone marrow functions defined as follows:&#xD;
&#xD;
               -  Neutrophil ≥1000/mm3 with no use of stimulating factor for at least 2 weeks prior&#xD;
                  to inclusion.&#xD;
&#xD;
               -  Lymphocytes ≥500/mm3&#xD;
&#xD;
               -  Platelets ≥ 50000/mm3.&#xD;
&#xD;
               -  Adequate hepatic functions defined as follows:&#xD;
&#xD;
               -  Direct bilirubin ≤1.5 x upper limit of normal (ULN)&#xD;
&#xD;
               -  AST/ALT ≤ 5 x ULN&#xD;
&#xD;
               -  Adequate renal function defined as follows:&#xD;
&#xD;
               -  Creatinine Clearance ≥70 ml/min/1.73m2 or serum Creatinine (Cr) as per&#xD;
                  age/gender.&#xD;
&#xD;
         11. Known history of Hepatitis B or C seropositivity with studies showing hepatic function&#xD;
             results within acceptable limits may be eligible.&#xD;
&#xD;
         12. Negative HIV serology.&#xD;
&#xD;
         13. Pregnancy test-negative for women of childbearing potential.&#xD;
&#xD;
         14. No previous Racotumomab therapy.&#xD;
&#xD;
         15. No previous intravenous immunoglobulin therapy for at least one month prior to the&#xD;
             beginning of treatment.&#xD;
&#xD;
         16. Lansky Scale ≥ 50 (Annex II)&#xD;
&#xD;
         17. Patients with extended bone metastasis in cranial vault or cranial base due to&#xD;
             proximity may be considered eligible.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        In order to be included, patients must not meet the following criteria:&#xD;
&#xD;
          1. Neuroblastoma as progressive disease at the time of the beginning of the study.&#xD;
&#xD;
          2. Patients with known hypersensitivity to any of the components of the investigational&#xD;
             drug.&#xD;
&#xD;
          3. Pregnant or breastfeeding patients.&#xD;
&#xD;
          4. Patients who have received other investigational drugs or Racotumomab within 30 days&#xD;
             prior to their inclusion in the protocol.&#xD;
&#xD;
          5. History of autoimmune diseases, congenital immunodeficiencies or uncontrolled chronic&#xD;
             diseases.&#xD;
&#xD;
          6. Acute allergy disorders or history of severe allergy reactions.&#xD;
&#xD;
          7. History of demyelinating disease or inflammatory disease of the central nervous system&#xD;
             or the peripheral nervous system.&#xD;
&#xD;
          8. Patients with any of the following uncontrolled intercurrent disease:&#xD;
&#xD;
               -  Active infectious diseases&#xD;
&#xD;
               -  Uncontrolled cardiac disease: symptomatic congestive heart failure, serious&#xD;
                  cardiac arrhythmia.&#xD;
&#xD;
               -  Known hepatic disease: cirrhosis, chronic active hepatitis or chronic persistent&#xD;
                  hepatitis.&#xD;
&#xD;
               -  Convulsions not controlled with any anticonvulsant medication.&#xD;
&#xD;
          9. Other malignancies after adequate therapy showing a disease-free period for more than&#xD;
             5 years.&#xD;
&#xD;
         10. Patients receiving chronic therapy with systemic steroids and other immunosuppressive&#xD;
             agents. Topical steroids and inhaled corticosteroids are permitted.&#xD;
&#xD;
         11. History of positive HIV serology.&#xD;
&#xD;
         12. Clinically symptomatic metastasis in central nervous system.&#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>Walter Cacciavillano, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Prof. Dr. J. P. Garrahan National Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universitario Austral</name>
      <address>
        <city>Pilar</city>
        <state>Buenos Aires</state>
        <zip>1629</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prof. Dr. J. P. Garrahan National Children's Hospital</name>
      <address>
        <city>Buenos Aires</city>
        <zip>1245</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>September 7, 2023</last_update_submitted>
  <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2023</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>Neuroblastoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT02998983
org study id: AR-RACO-2-16
nct id: NCT02998983
lead sponsor: 
has dmc: No
This clinical trial will be carried out in children diagnosed with high-risk neuroblastoma
      that have achieved a complete or very good partial response after standard therapy. An
      additional cohort of children who could not achieve these response criteria or that relapsed
      after standard therapy but do not have progressive disease will receive Racotumomab together
      with metronomic chemotherapy.

      The main objectives of this study are to determine the immune response after one-year
      duration immunization with Racotumomab, to describe the response of Racotumomab therapy in
      minimal residual disease (MRD) in bone marrow and to describe the toxicity profile of
      Racotumomab.
Neuroblastoma is the most common extra-cranial tumor in childhood but prognosis is still
      poor, even with the advances in its treatment.

      New therapeutic strategies have been examined, and several immunotherapeutic approaches,
      including combined therapy with monoclonal antibodies (anti-GD2), intravenous interleukin-2
      (Il-2) and intravenous granulocyte-macrophage colony-stimulating factor (GM-CSF), and
      anti-idiotype vaccines are currently being assessed.

      Racotumomab is an anti-idiotype antibody capable of inducing anti-N-glycolyl GM3 antibodies
      in patients with neuroblastoma.

      The expression of the ganglioside N-glycolyl GM3 was shown in neuroblastoma and this
      expression could be useful as a specific target for immunotherapy.

      Ractoumomab will be administered once standard therapy for neuroblastoma has been completed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants who elicit an immune response to a one-year immunization schedule of racotumomab in a cohort study of patients with high-risk neuroblastoma.
time frame: 1 year
measure: Number of participants in whom minimally disseminated disease in the bone marrow decreases or disappears with a one-year immunization schedule of racotumomab compared to baseline values at study entry.
time frame: 1 year
measure: Number of Participants With Treatment-Related Adverse Events as assessed by CTCAE v4.0 after a one-year immunization schedule of racotumomab when administered alone or together with onco-specific metronomic chemotherapy therapy.
time frame: 1 year
measure: Pattern of expression of N-Glycolyl-GM3 gangliosides in tumor samples obtained at disease diagnosis and during follow up if available.
time frame: 1 year
arm group label: Racotumomab
arm group type: Experimental
description: Dosage form: intradermal injection. Dosage: 0.4 mg. Frequency: the first 5 doses: biweekly injections; the following 10 doses: monthly injections. Duration: 12 months
intervention type: Drug
intervention name: Racotumomab
arm group label: Racotumomab
criteria: 
gender: All
minimum age: 1 Year
maximum age: 12 Years
healthy volunteers: No
last name: Walter Cacciavillano, MD
role: Principal Investigator
affiliation: Prof. Dr. J. P. Garrahan National Children's Hospital
facility: 
facility: 
country: Argentina
responsible party type: Sponsor
mesh term: Neuroblastoma
sharing ipd: No