<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/NCT02197637</url>
  </required_header>
  <id_info>
    <org_study_id>OVIMA-1210</org_study_id>
    <secondary_id>2013-001625-12</secondary_id>
    <secondary_id>PHRC 12- 194</secondary_id>
    <nct_id>NCT02197637</nct_id>
  </id_info>
  <brief_title>Phase II Trial of Oral Vinorelbine in Children With Recurrent or Progressive Unresectable Low-Grade Glioma</brief_title>
  <acronym>OVIMA-1210</acronym>
  <official_title>Phase II Trial of Oral Vinorelbine in Children With Recurrent or Progressive Unresectable Low-Grade Glioma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Oscar Lambret</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pierre Fabre Laboratories</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre Oscar Lambret</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>
      The purpose of this study is to determine whether oral vinorelbine is effective in the&#xD;
      treatment of children with progressive or recurrent unresectable low grade glioma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of this study is to determine efficacy of oral vinorelbine in children with&#xD;
      progressive or recurrent unresectable low grade glioma, in addition to safety,&#xD;
      pharmacokinetic, pharmacogenetic, medical costs and quality of life.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2014</start_date>
  <completion_date type="Actual">October 2020</completion_date>
  <primary_completion_date type="Actual">August 2019</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>Progression free survival</measure>
    <time_frame>9 months</time_frame>
    <description>no progressive disease according to RANO criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>6 months</time_frame>
    <description>Complete, partial and minor responses according to RANO criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>12 months</time_frame>
    <description>Complete, partial and minor responses according to RANO criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival PFS</measure>
    <time_frame>36 months</time_frame>
    <description>No progressive disease according to RANO criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival OS</measure>
    <time_frame>36 months</time_frame>
    <description>Death incidence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Growth Modulation Index GMI</measure>
    <time_frame>36 months</time_frame>
    <description>GMI defined as PFS2/ PSF1 ratio (PFS2 = PFS since the beginning of study treatment ; PFS1 = PFS observed in previous line of treatment)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>12 months</time_frame>
    <description>According to NCI-CTC AE scale v4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modifications of tumor aspects in diffusion and perfusion MRI</measure>
    <time_frame>At each tumor assessment, after 3, 6, 9 and 12 cycles of treatment, at the end of study, then every 4 months during the first year post therapy, then every 6 months for 3 years, if no prior progressive disease</time_frame>
    <description>Cerebral and/or spinal MRI (morphological and functional) with 2 dimensional assessment of target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Constitutional polymorphisms of cyp3A5, ABCB1</measure>
    <time_frame>Before the start of treatment</time_frame>
    <description>Single nucleotide polymorphisms (SNPs) will be analyzed by real time PCR and correlated with efficacy and toxicity of vinorelbine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic</measure>
    <time_frame>cycles 1 and 2, prior to the initial dose, 30 min, 1, 1.5, 2, 3, 6, 8, 10 and 26 hours post-dose</time_frame>
    <description>Plasmatic concentrations measured by LC-MS/MS (liquid chromatography tandem mass spectrometry) ; Area under the curve (AUC), maximal concentration (Cmax), time to Cmax (Tmax).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medical costs</measure>
    <time_frame>during all the study (up to 1 year)</time_frame>
    <description>Costs of medical care including : hospitalisations, emergency admissions, nursing care at home, medical consultations, diet support...</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Utilities Index (HUI)</measure>
    <time_frame>Before the treatment, then at day 1 of 1st cycle, after the 3th, 6th, 9th and the 12th cycles of study treatment, and at the end of study (up to 1 year)</time_frame>
    <description>Health Utilities Index (HUI)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Low-Grade Glioma</condition>
  <arm_group>
    <arm_group_label>ORAL VINORELBINE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Orally vinorelbine 60 mg/m2 D1, 8 and 15 Cycle of 28 days For a maximum of 12 cycles The dose of vinorelbine should be increased to 80 mg/m2 from the 2nd cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ORAL VINORELBINE</intervention_name>
    <description>Orally vinorelbine 60 mg/m2 D1, 8 and 15 Cycle of 28 days For a maximum of 12 cycles The dose of vinorelbine should be increased to 80 mg/m2 from the 2nd cycle If on D8 and D15, the administration conditions are not met, the administration is canceled and not delayed.</description>
    <arm_group_label>ORAL VINORELBINE</arm_group_label>
    <other_name>NAVELBINE</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        TUMOR CHARACTERISTICS:&#xD;
&#xD;
          -  Histologically confirmed recurrent or progressive primary Low-Grade Glioma (LGG)&#xD;
             defined as follow (WHO classification 2007): optic pathway glioma (OPG), pilocytic&#xD;
             astrocytoma (PA), fibrillary or diffuse astrocytoma (DA), oligodendroglioma (OG) or&#xD;
             oligoastrocytoma (OA)&#xD;
&#xD;
          -  Patients with OPG do not require biopsy confirmation of disease, if clinical and&#xD;
             radiological findings as well as ophthalmological examination are unequivocal&#xD;
&#xD;
          -  Low-Grade Glioma involving the brainstem can be included in case of histological&#xD;
             confirmation&#xD;
&#xD;
          -  Tumor has to be considered as non totally resectable&#xD;
&#xD;
        PATIENT CHARACTERISTICS:&#xD;
&#xD;
          -  Age 6-18 years old&#xD;
&#xD;
          -  Lansky or Karnofsky status more than 50 %&#xD;
&#xD;
          -  Measurable disease on cerebral and/or spinal MRI, with at least 1 lesion diameter&#xD;
             superior to 1 cm&#xD;
&#xD;
          -  Patients with metastatic disease are eligible, but at least 1 lesion must be&#xD;
             measurable as previously defined&#xD;
&#xD;
          -  Patients must have received at least 1 prior chemotherapy regimen containing&#xD;
             carboplatin&#xD;
&#xD;
          -  Life expectancy of at least 3 months&#xD;
&#xD;
          -  Evidence of adequate organ functions, including:&#xD;
&#xD;
          -  neutrophil count (ANC) ≥ 1500/mm3 ,&#xD;
&#xD;
          -  platelet count ≥100 000/mm3 ;&#xD;
&#xD;
          -  serum creatinine &lt; 1.5 x normal for age when the serum creatinine is ≥ 1.5 × the ULN,&#xD;
             the glomerular filtration rate (either estimated or formal) must be &gt; 70&#xD;
             mL/min/1.73m2;&#xD;
&#xD;
          -  total bilirubin&lt; 1.5 x normal for age,&#xD;
&#xD;
          -  ASAT and ALAT &lt; 2.5 x normal for age&#xD;
&#xD;
          -  Effective contraception for patients (male and female) with reproductive potential,&#xD;
             and for a minimum of 3 months after the end of treatment&#xD;
&#xD;
          -  Negative pregnancy test, if applicable&#xD;
&#xD;
          -  Patients able to swallow capsules&#xD;
&#xD;
          -  Patient affiliated with a health insurance system&#xD;
&#xD;
          -  Written informed consent of patient and/or parents/guardians prior to the study&#xD;
             participation.&#xD;
&#xD;
        PRIOR OR CONCURRENT THERAPY&#xD;
&#xD;
          -  Prior treatments containing vinca alkaloids like vincristine and/or vinblastine are&#xD;
             authorized&#xD;
&#xD;
          -  Patients must have fully recovered from the toxic effects of any prior therapy before&#xD;
             entering the study. No organ toxicity superior to grade 2 according to NCI-CTCAE v4.0&#xD;
&#xD;
          -  An interval of at least 2 months from prior radiotherapy, 6 weeks from nitrosourea&#xD;
             chemotherapy, and 4 weeks from other chemotherapy regimen, is required&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inclusion criteria failure&#xD;
&#xD;
          -  Prior treatment with intravenous or oral vinorelbine&#xD;
&#xD;
          -  Known hypersensibility to other vinca-alkaloïdes&#xD;
&#xD;
          -  Digestive pathology affecting absorption in a important way&#xD;
&#xD;
          -  Prior surgical resection of stomach or the small intestine&#xD;
&#xD;
          -  Severe hepatic failure independent from tumoral disease&#xD;
&#xD;
          -  Fructose intolerance&#xD;
&#xD;
          -  Leptomeningeal relapse without any available measurable disease on MRI (for example,&#xD;
             leptomeningeal relapse with totally resected primary lesion)&#xD;
&#xD;
          -  Uncontrolled active infection within 2 weeks&#xD;
&#xD;
          -  Pregnancy or breast feeding woman&#xD;
&#xD;
          -  Uncontrolled intercurrent illness or active infection&#xD;
&#xD;
          -  Unsuitable for medical follow-up (geographic, social or mental reasons)&#xD;
&#xD;
          -  Patients requiring long-term oxygen therapy&#xD;
&#xD;
          -  Patients with ANC less than 1500/mm3&#xD;
&#xD;
          -  Patients vaccinated against yellow fever&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pierre LEBLOND, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Oscar Lambret, Lille, France</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nicolas ANDRE, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hôpital La Timone, Marseille, France</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU d'Angers</name>
      <address>
        <city>Angers</city>
        <zip>49033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Bordeaux</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Grenoble</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Oscar Lambret</name>
      <address>
        <city>Lille</city>
        <zip>59020</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Limoges</name>
      <address>
        <city>Limoges</city>
        <zip>87042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Léon Bérard</name>
      <address>
        <city>Lyon</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de la TIMONE</name>
      <address>
        <city>Marseille</city>
        <zip>13385</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Arnaud de Villeneuve</name>
      <address>
        <city>Montpellier</city>
        <zip>34000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Nancy</name>
      <address>
        <city>Nancy</city>
        <zip>54500</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Curie</name>
      <address>
        <city>Paris</city>
        <zip>75005</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Reims</name>
      <address>
        <city>Reims</city>
        <zip>51100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Rennes - Hôpital Sud</name>
      <address>
        <city>Rennes</city>
        <zip>35203</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Rouen</name>
      <address>
        <city>Rouen</city>
        <zip>76031</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Hautepierre</name>
      <address>
        <city>Strasbourg</city>
        <zip>67098</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital des Enfants</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>May 9, 2014</study_first_submitted>
  <study_first_submitted_qc>July 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 23, 2014</study_first_posted>
  <last_update_submitted>November 17, 2020</last_update_submitted>
  <last_update_submitted_qc>November 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 18, 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>Glioma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vinorelbine</mesh_term>
  </intervention_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/NCT02197637
org study id: OVIMA-1210
secondary id: 2013-001625-12
secondary id: PHRC 12- 194
nct id: NCT02197637
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine whether oral vinorelbine is effective in the
      treatment of children with progressive or recurrent unresectable low grade glioma.
The aim of this study is to determine efficacy of oral vinorelbine in children with
      progressive or recurrent unresectable low grade glioma, in addition to safety,
      pharmacokinetic, pharmacogenetic, medical costs and quality of life.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival
time frame: 9 months
description: no progressive disease according to RANO criteria
measure: Response rate
time frame: 6 months
description: Complete, partial and minor responses according to RANO criteria
measure: Response rate
time frame: 12 months
description: Complete, partial and minor responses according to RANO criteria
measure: Progression Free Survival PFS
time frame: 36 months
description: No progressive disease according to RANO criteria
measure: Overall Survival OS
time frame: 36 months
description: Death incidence
measure: Growth Modulation Index GMI
time frame: 36 months
description: GMI defined as PFS2/ PSF1 ratio (PFS2 = PFS since the beginning of study treatment ; PFS1 = PFS observed in previous line of treatment)
measure: Adverse events
time frame: 12 months
description: According to NCI-CTC AE scale v4.0
measure: Modifications of tumor aspects in diffusion and perfusion MRI
time frame: At each tumor assessment, after 3, 6, 9 and 12 cycles of treatment, at the end of study, then every 4 months during the first year post therapy, then every 6 months for 3 years, if no prior progressive disease
description: Cerebral and/or spinal MRI (morphological and functional) with 2 dimensional assessment of target lesions.
measure: Constitutional polymorphisms of cyp3A5, ABCB1
time frame: Before the start of treatment
description: Single nucleotide polymorphisms (SNPs) will be analyzed by real time PCR and correlated with efficacy and toxicity of vinorelbine
measure: Pharmacokinetic
time frame: cycles 1 and 2, prior to the initial dose, 30 min, 1, 1.5, 2, 3, 6, 8, 10 and 26 hours post-dose
description: Plasmatic concentrations measured by LC-MS/MS (liquid chromatography tandem mass spectrometry) ; Area under the curve (AUC), maximal concentration (Cmax), time to Cmax (Tmax).
measure: Medical costs
time frame: during all the study (up to 1 year)
description: Costs of medical care including : hospitalisations, emergency admissions, nursing care at home, medical consultations, diet support...
measure: Health Utilities Index (HUI)
time frame: Before the treatment, then at day 1 of 1st cycle, after the 3th, 6th, 9th and the 12th cycles of study treatment, and at the end of study (up to 1 year)
description: Health Utilities Index (HUI)
arm group label: ORAL VINORELBINE
arm group type: Experimental
description: Orally vinorelbine 60 mg/m2 D1, 8 and 15 Cycle of 28 days For a maximum of 12 cycles The dose of vinorelbine should be increased to 80 mg/m2 from the 2nd cycle
intervention type: Drug
intervention name: ORAL VINORELBINE
description: Orally vinorelbine 60 mg/m2 D1, 8 and 15 Cycle of 28 days For a maximum of 12 cycles The dose of vinorelbine should be increased to 80 mg/m2 from the 2nd cycle If on D8 and D15, the administration conditions are not met, the administration is canceled and not delayed.
arm group label: ORAL VINORELBINE
other name: NAVELBINE
criteria: 
gender: All
minimum age: 6 Years
maximum age: 17 Years
healthy volunteers: No
last name: Pierre LEBLOND, MD, PhD
role: Principal Investigator
affiliation: Centre Oscar Lambret, Lille, France
last name: Nicolas ANDRE, MD, PhD
role: Principal Investigator
affiliation: Hôpital La Timone, Marseille, France
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Glioma
mesh term: Vinorelbine
sharing ipd: No