<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/NCT01666600</url>
  </required_header>
  <id_info>
    <org_study_id>NONK-3/NOA-12</org_study_id>
    <nct_id>NCT01666600</nct_id>
  </id_info>
  <brief_title>NOA-12: BIBF1120 and R-RT in Glioblastoma</brief_title>
  <official_title>A Phase I/II, Randomized, Open-label, Multi-centre Study of BIBF1120 + Reirradiation (R-RT) Versus Reirradiation in the Treatment of Patients With First or Second Progression of Glioblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Prof. Dr. Wolfgang Wick</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital Heidelberg</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with glioblastoma at first or second progression who have failed standard treatment&#xD;
      that must have included radiochemotherapy with temozolomide and who are a candidate for a&#xD;
      reirradiation can be included into the trial. In the phase I part the minimal tolerated dose&#xD;
      (MTD)of BIBF 1120 in combination with radiotherapy will be investigated. Subjects in phase II&#xD;
      will be randomised to receive reirradiation alone or reirradiation + 2 x MTD BIBF1120.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Interim Analysis for Feasibility&#xD;
  </why_stopped>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">September 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximal tolerated dose of BIBF 1120 in combination with reirradiation (Phase I)</measure>
    <time_frame>day 0, 8, 15 and 17 post-dose during phase I</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with adverse events as a measure of safety and tolerability of BIBF1120</measure>
    <time_frame>Up to 90 days follow-up</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Time from randomization until death or disease progression</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rates (OR)</measure>
    <time_frame>Time from randomization until response</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Time from randomization until death</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life as determined by EORTC QLQ-C15 PAL and the EORTC brain module QLQ-BN 20</measure>
    <time_frame>Screening and 6-weekly after radiotherapy</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function determined by MMSE</measure>
    <time_frame>Screening and 6-weekly after end of radiotherapy</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">63</enrollment>
  <condition>Glioblastoma Multiforme</condition>
  <arm_group>
    <arm_group_label>BIBF 1120 + reirradiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 x minimal tolerated dose BIBF 1120 per day in combination with radiotherapy (2 Gy / fraction; 36 Gy in total)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>reirradiation alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>radiotherapy (2 Gy / fraction; 36 Gy in total)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIBF 1120</intervention_name>
    <description>BIBF 1120 is given as 2 x minimal tolerated dose per day as long as as a clinical benefit is considered by the treating physician.</description>
    <arm_group_label>BIBF 1120 + reirradiation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>radiotherapy</intervention_name>
    <description>36 Gy, 2 Gy / fraction, 18 fractions</description>
    <arm_group_label>reirradiation alone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients with a recurrence / progression of glioblastoma either not&#xD;
             being eligible for tumour resection or having macroscopic residual tumour after&#xD;
             resection of the recurrence&#xD;
&#xD;
          -  Diagnosis of glioblastoma must be proven histologically and progress must be&#xD;
             documented by MRI. MRI images must not be older than 2 weeks before first dosing/start&#xD;
             of RT&#xD;
&#xD;
          -  Not more than two prior therapy regimens including one or two resections, one or two&#xD;
             chemotherapies (one temozolomide containing concomitant to radiotherapy) and one&#xD;
             radiotherapy (RT) for the brain tumour&#xD;
&#xD;
          -  Previous irradiation therapy of the primary tumour with a maximal dose of 60 Gy; at&#xD;
             least 8 months since the end of preirradiation&#xD;
&#xD;
          -  Candidate for reirradiation with recurrent tumour visible on MRIT1 (Gd) and with the&#xD;
             largest diameter measuring 1 cm to 5 cm&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
          -  Age ≥ 18 years, smoking or non-smoking, of any ethnic origin&#xD;
&#xD;
          -  Karnofsky performance index (KPI) ≥ 60%&#xD;
&#xD;
          -  Neutrophile counts &gt; 1500/μl / Platelet counts &gt; 80.000/μl /Haemoglobin &gt; 10 g/dl /&#xD;
             Serum creatinine &lt; 1.5-fold upper normal range / Bilirubin, AST or ALT &lt; 2,5-fold&#xD;
             upper normal range unless attributed to anticonvulsants / Alkaline phosphatase &lt;&#xD;
             2,5-fold upper normal range&#xD;
&#xD;
          -  Adequate contraception&#xD;
&#xD;
          -  If on steroids, stable or decreasing treatment with steroids within 5 days before&#xD;
             treatment start&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  More than one RT of brain, prior first radiotherapy with more than 60 Gy&#xD;
&#xD;
          -  Cumulative total dose on the optical chiasm &gt;54 Gy for 2 Gy/fraction, α/β=2&#xD;
&#xD;
          -  Prior treatment with bevacizumab, iodine seeds and/or brachytherapy&#xD;
&#xD;
          -  Unable to undergo MRI&#xD;
&#xD;
          -  Past medical history of diseases with poor prognosis according to the judgement of the&#xD;
             Investigator, e.g. severe coronary heart disease, severe diabetes, immune deficiency,&#xD;
             residual deficits after stroke, severe mental retardation&#xD;
&#xD;
          -  HIV or hepatitis infection&#xD;
&#xD;
          -  Pregnancy or breast feeding&#xD;
&#xD;
          -  Treatment within any other clinical trial parallel to the treatment phase of the&#xD;
             current study or within 30 days before inclusion&#xD;
&#xD;
          -  Known coronary artery disease, significant cardiac arrhythmias or severe congestive&#xD;
             heart failure (NYHA class III - IV)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University Hospital Heidelberg, Department of Neurooncology</name>
      <address>
        <city>Heidelberg</city>
        <state>Baden-Württemberg</state>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Heidelberg, Department of Pharmacology</name>
      <address>
        <city>Heidelberg</city>
        <state>Baden-Württemberg</state>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>July 12, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>October 30, 2017</last_update_submitted>
  <last_update_submitted_qc>October 30, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital Heidelberg</investigator_affiliation>
    <investigator_full_name>Prof. Dr. Wolfgang Wick</investigator_full_name>
    <investigator_title>Professor Dr. med.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nintedanib</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01666600
org study id: NONK-3/NOA-12
nct id: NCT01666600
lead sponsor: 
has dmc: Yes
Patients with glioblastoma at first or second progression who have failed standard treatment
      that must have included radiochemotherapy with temozolomide and who are a candidate for a
      reirradiation can be included into the trial. In the phase I part the minimal tolerated dose
      (MTD)of BIBF 1120 in combination with radiotherapy will be investigated. Subjects in phase II
      will be randomised to receive reirradiation alone or reirradiation + 2 x MTD BIBF1120.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximal tolerated dose of BIBF 1120 in combination with reirradiation (Phase I)
time frame: day 0, 8, 15 and 17 post-dose during phase I
measure: Number of participants with adverse events as a measure of safety and tolerability of BIBF1120
time frame: Up to 90 days follow-up
measure: Progression-free survival
time frame: Time from randomization until death or disease progression
measure: Objective response rates (OR)
time frame: Time from randomization until response
measure: Overall survival
time frame: Time from randomization until death
measure: Quality of life as determined by EORTC QLQ-C15 PAL and the EORTC brain module QLQ-BN 20
time frame: Screening and 6-weekly after radiotherapy
measure: Cognitive function determined by MMSE
time frame: Screening and 6-weekly after end of radiotherapy
arm group label: BIBF 1120 + reirradiation
arm group type: Experimental
description: 2 x minimal tolerated dose BIBF 1120 per day in combination with radiotherapy (2 Gy / fraction; 36 Gy in total)
arm group label: reirradiation alone
arm group type: Active Comparator
description: radiotherapy (2 Gy / fraction; 36 Gy in total)
intervention type: Drug
intervention name: BIBF 1120
description: BIBF 1120 is given as 2 x minimal tolerated dose per day as long as as a clinical benefit is considered by the treating physician.
arm group label: BIBF 1120 + reirradiation
intervention type: Radiation
intervention name: radiotherapy
description: 36 Gy, 2 Gy / fraction, 18 fractions
arm group label: reirradiation alone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: Germany
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital Heidelberg
investigator full name: Prof. Dr. Wolfgang Wick
investigator title: Professor Dr. med.
mesh term: Glioblastoma
mesh term: Nintedanib