<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/NCT04469699</url>
  </required_header>
  <id_info>
    <org_study_id>UKM12_0017</org_study_id>
    <secondary_id>2015-002727-25</secondary_id>
    <nct_id>NCT04469699</nct_id>
  </id_info>
  <brief_title>Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma</brief_title>
  <acronym>NOA11</acronym>
  <official_title>Controlled Clinical Trial to Evaluate the Safety and Efficacy of Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Muenster</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Deutsche Krebshilfe e.V., Bonn (Germany)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>photonamic GmbH &amp; Co. KG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>medac GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>LifePhotonic GmbH</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital Muenster</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>
      In this multicenter, randomized, non-blinded trial the efficacy and safety of stereotactical&#xD;
      photodynamic therapy with 5-aminolevulinic acid will be investigated in 106 patients with&#xD;
      recurrent glioblastoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 12, 2021</start_date>
  <completion_date type="Anticipated">April 2026</completion_date>
  <primary_completion_date type="Anticipated">April 2026</primary_completion_date>
  <phase>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>Progression free survival (PFS)</measure>
    <time_frame>through study completion (at least 1.5 years and a maximum of 5 years) or until progression or death</time_frame>
    <description>Progression free survival (PFS) measured as time from the day of randomization until diagnosis of progressive disease as determined by MRI according to RANO criteria (Response Assessment in Neuro-Oncology Criteria) or death from any cause</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>6-month PFS rate</measure>
    <time_frame>for each patient up to 6 months after randomization or until progression has occurred</time_frame>
    <description>Progression free survival (PFS) measured as time from the day of randomization until diagnosis of progressive disease as determined by MRI according to RANO criteria or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>through study completion (at least 1.5 years and a maximum of 5 years) or until death</time_frame>
    <description>Overall survival (OS) measured as time from the day of randomization until death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free time</measure>
    <time_frame>through study completion (at least 1.5 years and a maximum of 5 years) or until progression</time_frame>
    <description>Progression free time as time from the day of randomization until progressive disease (death is regarded as censored)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>12-month OS rate</measure>
    <time_frame>for each patient up to 12 months after randomization or until death</time_frame>
    <description>Overall survival (OS) measured as time from the day of randomization until death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute changes from baseline in contrast medium volume uptake from the MRI performed 48 hours after randomization on, and during any MRI performed thereafter to monitor for disease progression</measure>
    <time_frame>Baseline, 26 - 48 hours after stereotactic procedure, 1 month after randomization and then every 2 months, 1.5 years after randomization or at disease progression, and then every 3 months until end of entire study (up to 5 years) or progression</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>48h response rate on MRI (Complete Remission, Partial Remission, Stable Disease) after treatment with iPDT (interstitial photodynamic therapy)</measure>
    <time_frame>26 - 48 hours after stereotactic procedure in patients treated with interstitial photodynamic therapy (iPDT)</time_frame>
    <description>Response is assessed according to the RANO criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>If a PET (positron emission tomography) was performed less than 2 weeks apart from an MRI: Consistency of both procedures with regard to the region of interest (ROI)</measure>
    <time_frame>Baseline, 26 - 48 hours after stereotactic procedure, 1 month after randomization and then every 2 months, 1.5 years after randomization or at disease progression and then every 3 months until end of entire study (up to 5 years) or progression</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in KPS (Karnofsky Performance Score)</measure>
    <time_frame>Baseline, 26 -48 hours after stereotactic procedure, upon discharge or 7 days after stereotactic procedure, 1 month after randomization and then every 2 months until 1.5 years after randomization or disease progression</time_frame>
    <description>Minimum value: 0, maximum value: 100. A higher value means a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in NIHSS (National Institutes of Health Stroke Scale)</measure>
    <time_frame>Baseline, 26 -48 hours after stereotactic procedure, upon discharge or 7 days after stereotactic procedure, 1 month after randomization and then every 2 months until 1.5 years after randomization or disease progression</time_frame>
    <description>Minimum value: 0, maximum value: 42. A higher value means a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in MMSE (Mini-Mental State Examination)</measure>
    <time_frame>Baseline, 26 -48 hours after stereotactic procedure, upon discharge or 7 days after stereotactic procedure, 1 month after randomization and then every 2 months until 1.5 years after randomization or disease progression</time_frame>
    <description>Minimum value: 0, maximum value: 30. A higher value means a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brain edema as assessed by MRI within 26 to 48 h after stereotactic surgery</measure>
    <time_frame>26 to 48 hours after stereotactic intervention</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of Adverse Events</measure>
    <time_frame>over the entire study period of each patient (at least 1.5 years and a maximum of 5 years)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire) score during study participation</measure>
    <time_frame>Baseline, at discharge or 7 days after intervention, 1 month after randomization and then every 2 months, 1.5 years after randomization or at disease progression and then every 3 months until end of entire study (up to 5 years) or progression</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the EORTC QLQ-BN20 module (European Organisation for Research and Treatment of Cancer Quality of Life Brain Cancer Module) score during study participation</measure>
    <time_frame>Baseline, at discharge or 7 days after intervention, 1 month after randomization and then every 2 months, 1.5 years after randomization or at disease progression and then every 3 months until end of entire study (up to 5 years) or progression</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">106</enrollment>
  <condition>Glioblastoma Multiforme, Adult</condition>
  <arm_group>
    <arm_group_label>Treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Stereotactic biopsy followed by stereotactical photodynamic therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Stereotactic biopsy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Stereotactic biopsy followed by stereotactical photodynamic therapy with 5-aminolevulinic acid</intervention_name>
    <description>5-ALA HCl orally (20 mg/kg bw) 3,5-4,5 hours prior to induction of anaesthesia for stereotactic biopsy followed by stereotactical photodynamic therapy. All patients will receive further treatment of recurrent glioblastoma at the investigator´s discretion (best possible care).</description>
    <arm_group_label>Treatment arm</arm_group_label>
    <other_name>Gliolan, 5-aminolevulinic acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Stereotactic biopsy</intervention_name>
    <description>Stereotactic biopsy. All patients will receive further treatment of recurrent glioblastoma at the investigator´s discretion (best possible care).</description>
    <arm_group_label>Control arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent&#xD;
&#xD;
          2. Age 18 - 75 years&#xD;
&#xD;
          3. Karnofsky Performance Score (KPS) of ≥60 %&#xD;
&#xD;
          4. Radiologically suspected diagnosis (according to RANO criteria) of the first&#xD;
             recurrence of a glioblastoma located in the cerebral hemisphere including insular and&#xD;
             diencephalon. Tumors in the brain stem are excluded. First MRI with signs of first&#xD;
             recurrence (radiologic RANO criteria for disease progression) within 8 weeks prior to&#xD;
             Informed Consent. Not necessarily identical to primary tumor location&#xD;
&#xD;
          5. Single or single progressive contrast-enhancing lesion on MRI, largest diameter not&#xD;
             more than 2.5 cm&#xD;
&#xD;
          6. For female and male patients of reproductive potential: Willingness to apply highly&#xD;
             effective contraception (Pearl index &lt;1) during the entire study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Multifocal disease &gt; 2 locations&#xD;
&#xD;
          2. Patients with significant non-enhancing tumor portions&#xD;
&#xD;
          3. Previous treatment of recurrence&#xD;
&#xD;
          4. Other malignant disease except basalioma&#xD;
&#xD;
          5. Hypersensitivity against porphyrins or Gliolan® or Fluorethylenpropylen (FEP )&#xD;
&#xD;
          6. Porphyria&#xD;
&#xD;
          7. HIV infection, active Hepatitis B or C infection&#xD;
&#xD;
          8. Bone marrow reserve:&#xD;
&#xD;
               -  white blood cell (WBC) count &lt;2000/μl,&#xD;
&#xD;
               -  platelets &lt;100000/μl,&#xD;
&#xD;
          9. Liver function:&#xD;
&#xD;
               -  total bilirubin &gt; 1.5 times above upper limit of normal range (ULN)&#xD;
&#xD;
               -  alanine transaminase (ALT) and aspartate transaminase (AST) &gt; 3 times ULN&#xD;
&#xD;
         10. Renal function:&#xD;
&#xD;
             - creatinine &gt; 1.5 times ULN&#xD;
&#xD;
         11. Blood clotting:&#xD;
&#xD;
             - Quick/INR or PTT out of acceptable limits&#xD;
&#xD;
         12. Conditions precluding MRI (e.g. pacemaker)&#xD;
&#xD;
         13. Past medical history of diseases with poor prognosis, e.g. severe coronary heart&#xD;
             disease, heart failure (NYHA III/IV), severe poorly controlled diabetes, immune&#xD;
             deficiency, residual deficits after stroke, severe mental retardation or other serious&#xD;
             concomitant systemic disorders incompatible with the study (at the discretion of the&#xD;
             investigator)&#xD;
&#xD;
         14. Any active infection (at the discretion of the investigator)&#xD;
&#xD;
         15. Any psychological, cognitive, familial, sociological or geographical condition that,&#xD;
             in the investigator's opinion, compromises the patient's ability to understand the&#xD;
             patient information, to give informed consent or to comply with the trial protocol&#xD;
&#xD;
         16. Previous antiangiogenic treatment&#xD;
&#xD;
         17. Participation in another interventional clinical trial during this trial or within 4&#xD;
             weeks before entry into this trial.&#xD;
&#xD;
         18. Pregnancy or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Walter Stummer, Univ.-Prof. Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Muenster, Klinik und Poliklinik für Neurochirurgie</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Juliane Schroeteler, Dr. med.</last_name>
    <phone>+491733802878</phone>
    <email>juliane.schroeteler@ukmuenster.de</email>
  </overall_contact>
  <location>
    <facility>
      <name>Medizinische Fakultät Carl Gustav Carus, Klinik und Poliklinik für Neurochirurgie</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Abteilung Funktionelle NC &amp; Stereotaxie</name>
      <address>
        <city>Düsseldorf</city>
        <zip>40225</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Essen, Klinik für Neurochirurgie und Wirbelsäulenchirurgie</name>
      <address>
        <city>Essen</city>
        <zip>45122</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>LMU München, Campus Großhadern, Neurochirurgische Klinik und Poliklinik</name>
      <address>
        <city>München</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Münster, Klinik und Poliklinik für Neurochirurgie</name>
      <address>
        <city>Münster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>May 12, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>December 20, 2022</last_update_submitted>
  <last_update_submitted_qc>December 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2022</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>Glioblastoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aminolevulinic Acid</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/NCT04469699
org study id: UKM12_0017
secondary id: 2015-002727-25
nct id: NCT04469699
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In this multicenter, randomized, non-blinded trial the efficacy and safety of stereotactical
      photodynamic therapy with 5-aminolevulinic acid will be investigated in 106 patients with
      recurrent glioblastoma.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival (PFS)
time frame: through study completion (at least 1.5 years and a maximum of 5 years) or until progression or death
description: Progression free survival (PFS) measured as time from the day of randomization until diagnosis of progressive disease as determined by MRI according to RANO criteria (Response Assessment in Neuro-Oncology Criteria) or death from any cause
measure: 6-month PFS rate
time frame: for each patient up to 6 months after randomization or until progression has occurred
description: Progression free survival (PFS) measured as time from the day of randomization until diagnosis of progressive disease as determined by MRI according to RANO criteria or death from any cause
measure: Overall survival (OS)
time frame: through study completion (at least 1.5 years and a maximum of 5 years) or until death
description: Overall survival (OS) measured as time from the day of randomization until death
measure: Progression free time
time frame: through study completion (at least 1.5 years and a maximum of 5 years) or until progression
description: Progression free time as time from the day of randomization until progressive disease (death is regarded as censored)
measure: 12-month OS rate
time frame: for each patient up to 12 months after randomization or until death
description: Overall survival (OS) measured as time from the day of randomization until death
measure: Absolute changes from baseline in contrast medium volume uptake from the MRI performed 48 hours after randomization on, and during any MRI performed thereafter to monitor for disease progression
time frame: Baseline, 26 - 48 hours after stereotactic procedure, 1 month after randomization and then every 2 months, 1.5 years after randomization or at disease progression, and then every 3 months until end of entire study (up to 5 years) or progression
measure: 48h response rate on MRI (Complete Remission, Partial Remission, Stable Disease) after treatment with iPDT (interstitial photodynamic therapy)
time frame: 26 - 48 hours after stereotactic procedure in patients treated with interstitial photodynamic therapy (iPDT)
description: Response is assessed according to the RANO criteria
measure: If a PET (positron emission tomography) was performed less than 2 weeks apart from an MRI: Consistency of both procedures with regard to the region of interest (ROI)
time frame: Baseline, 26 - 48 hours after stereotactic procedure, 1 month after randomization and then every 2 months, 1.5 years after randomization or at disease progression and then every 3 months until end of entire study (up to 5 years) or progression
measure: Change in KPS (Karnofsky Performance Score)
time frame: Baseline, 26 -48 hours after stereotactic procedure, upon discharge or 7 days after stereotactic procedure, 1 month after randomization and then every 2 months until 1.5 years after randomization or disease progression
description: Minimum value: 0, maximum value: 100. A higher value means a better outcome.
measure: Change in NIHSS (National Institutes of Health Stroke Scale)
time frame: Baseline, 26 -48 hours after stereotactic procedure, upon discharge or 7 days after stereotactic procedure, 1 month after randomization and then every 2 months until 1.5 years after randomization or disease progression
description: Minimum value: 0, maximum value: 42. A higher value means a worse outcome.
measure: Change in MMSE (Mini-Mental State Examination)
time frame: Baseline, 26 -48 hours after stereotactic procedure, upon discharge or 7 days after stereotactic procedure, 1 month after randomization and then every 2 months until 1.5 years after randomization or disease progression
description: Minimum value: 0, maximum value: 30. A higher value means a better outcome.
measure: Brain edema as assessed by MRI within 26 to 48 h after stereotactic surgery
time frame: 26 to 48 hours after stereotactic intervention
measure: Frequency of Adverse Events
time frame: over the entire study period of each patient (at least 1.5 years and a maximum of 5 years)
measure: Change in the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire) score during study participation
time frame: Baseline, at discharge or 7 days after intervention, 1 month after randomization and then every 2 months, 1.5 years after randomization or at disease progression and then every 3 months until end of entire study (up to 5 years) or progression
measure: Change in the EORTC QLQ-BN20 module (European Organisation for Research and Treatment of Cancer Quality of Life Brain Cancer Module) score during study participation
time frame: Baseline, at discharge or 7 days after intervention, 1 month after randomization and then every 2 months, 1.5 years after randomization or at disease progression and then every 3 months until end of entire study (up to 5 years) or progression
arm group label: Treatment arm
arm group type: Experimental
description: Stereotactic biopsy followed by stereotactical photodynamic therapy
arm group label: Control arm
arm group type: Other
description: Stereotactic biopsy
intervention type: Drug
intervention name: Stereotactic biopsy followed by stereotactical photodynamic therapy with 5-aminolevulinic acid
description: 5-ALA HCl orally (20 mg/kg bw) 3,5-4,5 hours prior to induction of anaesthesia for stereotactic biopsy followed by stereotactical photodynamic therapy. All patients will receive further treatment of recurrent glioblastoma at the investigator´s discretion (best possible care).
arm group label: Treatment arm
other name: Gliolan, 5-aminolevulinic acid
intervention type: Procedure
intervention name: Stereotactic biopsy
description: Stereotactic biopsy. All patients will receive further treatment of recurrent glioblastoma at the investigator´s discretion (best possible care).
arm group label: Control arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Walter Stummer, Univ.-Prof. Dr. med.
role: Principal Investigator
affiliation: University Hospital Muenster, Klinik und Poliklinik für Neurochirurgie
last name: Juliane Schroeteler, Dr. med.
phone: +491733802878
email: juliane.schroeteler@ukmuenster.de
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Not yet recruiting
facility: 
status: Recruiting
country: Germany
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Aminolevulinic Acid
sharing ipd: No