xml: <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/NCT06039709</url>
    </required_header>
    <id_info>
      <org_study_id>HSR230064</org_study_id>
      <nct_id>NCT06039709</nct_id>
    </id_info>
    <brief_title>Sonodynamic Therapy in Patients With Recurrent GBM</brief_title>
    <acronym>GBM 001</acronym>
    <official_title>Pilot Study of Sonodynamic Therapy With 5-ALA for the Treatment of Recurrent Glioblastoma Using Neuronavigation-Guided Low-Intensity Focused Ultrasound</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shayan Moosa, MD</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Virginia</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
      <is_unapproved_device>Yes</is_unapproved_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Patients diagnosed with glioblastoma (GBM) are faced with limited treatment options. This&#xD;
        pilot study will evaluate the safety and feasibility of combining an investigational drug&#xD;
        called 5-ALA with neuronavigation-guided low-intensity focused ultrasound (LIFU) for patients&#xD;
        who have recurrent GBM. Focused ultrasound (FUS) can be used to non-invasively destroy tumor&#xD;
        tissue while preserving normal tissue. When FUS is combined with 5-ALA, this combinatorial&#xD;
        approach is called sonodynamic therapy (SDT), and this investigational therapy is being&#xD;
        tested for its ability to cause damage to GBM cells. SDT will take place prior to surgery for&#xD;
        recurrent GBM.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The combination of 5-ALA (Gleolan) and LIFU is collectively known as sonodynamic therapy&#xD;
        (SDT). SDT is an investigational therapy that will be administered 1-3 weeks before surgery&#xD;
        for recurrent GBM. Researchers seek to determine the safety and feasibility of this therapy&#xD;
        as well as measure its effectiveness to elicit tumor-cell death. All participants are&#xD;
        expected to stay overnight in the hospital following administration of SDT to monitor for&#xD;
        adverse events.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">May 2026</completion_date>
    <primary_completion_date type="Anticipated">November 2025</primary_completion_date>
    <phase>Phase 1</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 adverse events</measure>
      <time_frame>From informed consent through 30 days after study intervention is complete</time_frame>
      <description>Per NCI Common Terminology Criteria for Adverse Events v5.0</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Severity of adverse events</measure>
      <time_frame>From informed consent through 30 days after study intervention is complete</time_frame>
      <description>Per NCI Common Terminology Criteria for Adverse Events v5.0</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of intracranial hemorrhage and/or worsening of edema</measure>
      <time_frame>From day after SDT (day 1) up to the time of surgery (day 7-day 21)</time_frame>
      <description>On post-SDT MRIs</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Extent of targeted tumor area receiving FUS</measure>
      <time_frame>Day 0</time_frame>
      <description>Use of NaviFUS system to target a maximum of 50% of the tumor volume of one contiguous lesion</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Ability to have participants undergo planned surgery without delay</measure>
      <time_frame>within 3 weeks following SDT</time_frame>
      <description>A delay is defined as more than 3 weeks after SDT</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Response of target tissue following SDT on imaging</measure>
      <time_frame>From day after SDT (day 1) up to 100 days after intervention is completed</time_frame>
      <description>Via MRI w/ use of modified Response Assessment in Neuro-Oncology (RANO) criteria</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Histologic tumor devitalization</measure>
      <time_frame>Day 7-Day 21</time_frame>
      <description>Evaluating cell fate and cell death via histologic samples after GBM resection</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">11</enrollment>
    <condition>Recurrent Glioblastoma</condition>
    <condition>Glioblastoma Multiforme</condition>
    <condition>GBM</condition>
    <arm_group>
      <arm_group_label>Sonodynamic Therapy (5-ALA + LIFU)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Administration of SDT occurs 1-3 weeks prior to GBM resection</description>
    </arm_group>
    <intervention>
      <intervention_type>Combination Product</intervention_type>
      <intervention_name>5-ALA and Low-Intensity Focused Ultrasound (SDT)</intervention_name>
      <description>5-ALA (20mg/kg orally) given ~6 hours prior to LIFU. Focused ultrasound will target a maximum of 50% of the tumor.</description>
      <arm_group_label>Sonodynamic Therapy (5-ALA + LIFU)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Disease status and Disease Parameters:&#xD;
  &#xD;
                 -  Suspected recurrent glioblastoma that is clearly measurable based on the modified&#xD;
                    Response Assessment in Neuro-Oncology (RANO) criteria&#xD;
  &#xD;
                 -  The tumor lesion needs to comprise at least 1 contrast-enhancing lesion with a&#xD;
                    volume of ≥ 6 cm3 and ≤ 20 cm3 of targeted treatment area&#xD;
  &#xD;
                 -  Tumor tissue to be treated is in a surgically accessible brain region for biopsy&#xD;
                    or resection&#xD;
  &#xD;
                 -  The brain tumor to be treated must be in the treatment envelope of the NaviFUS&#xD;
                    system (30 mm to 80 mm from the inner skull table)&#xD;
  &#xD;
                 -  Recurrence will be assessed by imaging and confirmed by consensus at tumor board&#xD;
  &#xD;
            2. Men or women between the ages of 18-80 years of age at the time of consent&#xD;
  &#xD;
            3. No contraindication to repeat brain surgery&#xD;
  &#xD;
            4. Karnofsky Performance Score of 70-100&#xD;
  &#xD;
            5. Able to undergo an MRI with contrast&#xD;
  &#xD;
            6. Able to swallow oral medications&#xD;
  &#xD;
            7. Willingness and ability to comply with scheduled visits, treatment plans, lifestyle&#xD;
               considerations, laboratory tests, and other procedures.&#xD;
  &#xD;
            8. Ability to understand and the willingness to sign a written informed consent document&#xD;
               (personally or by the legally authorized representative, if applicable).&#xD;
  &#xD;
            9. Participants who received prior chemotherapy, radiation therapy, immunotherapy, and/or&#xD;
               another investigational therapy must have recovered (Common Terminology Criteria for&#xD;
               Adverse Events [CTCAE] Grade ≤1 or baseline) from the acute effects of the therapy or&#xD;
               therapies) except for residual alopecia or Grade 2 peripheral neuropathy prior to&#xD;
               registration.&#xD;
  &#xD;
           10. Has adequate bone marrow and organ function as defined by the following laboratory&#xD;
               values (as assessed by the local laboratory for eligibility):&#xD;
  &#xD;
          Hematological&#xD;
  &#xD;
            -  Absolute neutrophil count (ANC) ≥1000/mm3&#xD;
  &#xD;
            -  Platelets ≥ 100,000/mm3&#xD;
  &#xD;
            -  Hemoglobin ≥ 11 g/dL for women and ≥ 12 g/dL for men Participants may receive&#xD;
               erythrocyte transfusions to achieve this hemoglobin level at the discretion of the&#xD;
               investigator.&#xD;
  &#xD;
            -  INR ≤ 1.4&#xD;
  &#xD;
          Renal &amp; Hepatic&#xD;
  &#xD;
            -  Creatinine clearance CrCl ≥ 60 mL/min/1.73 m2 as estimated by the Cockcroft-Gault&#xD;
               (C-G) equation. If estimated CrCl is abnormal, accurate measurement should be obtained&#xD;
               by 24- hour CrCl.&#xD;
  &#xD;
            -  Bilirubin ≤ 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to&#xD;
               2.0x ULN is allowed).&#xD;
  &#xD;
            -  AST and ALT ≤ 3 x ULN&#xD;
  &#xD;
            -  Alkaline phosphatase ≤ 3 x ULN&#xD;
  &#xD;
            -  GGT ≤ 3 x ULN&#xD;
  &#xD;
            -  Estimated glomerular filtration rate ≥30mL/min/1.73m2&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Known sensitivity or allergy to 5-ALA&#xD;
  &#xD;
            2. Simultaneous use of other potentially phototoxic substances (e.g. tetracyclines,&#xD;
               sulfonamides, fluoroquinolones, hypericin extracts)&#xD;
  &#xD;
            3. Diagnosis of porphyria&#xD;
  &#xD;
            4. Hypersensitivity against porphyrins&#xD;
  &#xD;
            5. Pregnancy&#xD;
  &#xD;
            6. Significant cardiac disease or coagulopathy&#xD;
  &#xD;
            7. Herniation / intractable seizure / other clinical indications requiring urgent&#xD;
               resection&#xD;
  &#xD;
            8. Known active systemic bacterial infection (requiring intravenous [IV] antibiotics at&#xD;
               time of initiating study treatment), fungal infection, or detectable viral infection&#xD;
               (such as known human immunodeficiency virus positivity or with known active hepatitis&#xD;
               B or C (for example, hepatitis B surface antigen positive)&#xD;
  &#xD;
            9. Have had a recent (≤3 months prior to registration) transient ischemic attack or&#xD;
               stroke&#xD;
  &#xD;
           10. Significant vascular disease (e.g. aortic aneurysm)&#xD;
  &#xD;
           11. Evidence of bleeding diathesis or coagulopathy&#xD;
  &#xD;
           12. Need for systemic anticoagulation which cannot be held for 7 days prior to SDT&#xD;
  &#xD;
           13. Unstable angina and/or congestive heart failure (NYH Class III or Class IV; see&#xD;
               section 13.2) within 6 months prior to registration&#xD;
  &#xD;
           14. Severe hypertension (systolic ≥ 180 mm Hg; diastolic ≥ 120 mm Hg) despite&#xD;
               anti-hypertensive medications&#xD;
  &#xD;
           15. Transmural myocardial infarction within 6 months prior to registration&#xD;
  &#xD;
           16. Serious and inadequately controlled cardiac arrhythmia&#xD;
  &#xD;
           17. Acute exacerbation of chronic obstructive pulmonary disease&#xD;
  &#xD;
           18. Has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment&#xD;
               of the investigator, would preclude participation in this study&#xD;
  &#xD;
           19. Treatment with another investigational drug within 30 days prior to registration or&#xD;
               within 5 half-lives of the investigational product, whichever is longer&#xD;
  &#xD;
           20. Brain edema and/or mass effect that causes midline shift of more than 15 mm&#xD;
  &#xD;
           21. Evidence of recent (within 30 days prior to registration) intracranial hemorrhage&#xD;
  &#xD;
           22. Calcifications or metallic implanted objects in the focused ultrasound sonication path&#xD;
  &#xD;
           23. Scalp atrophy or scars at the expected location of transducer&#xD;
  &#xD;
           24. Cerebral or systemic vasculopathy&#xD;
  &#xD;
           25. Need for or currently on dialysis&#xD;
  &#xD;
           26. Respiratory: chronic pulmonary disorders (e.g., severe emphysema, COPD, pulmonary&#xD;
               vasculitis, or other causes of reduced pulmonary vascular cross-sectional area).&#xD;
  &#xD;
           27. Receipt of radiotherapy ≤21 days prior to registration&#xD;
  &#xD;
           28. Receipt of any of the following ≤ 21 days prior to registration&#xD;
  &#xD;
                 -  chemotherapy&#xD;
  &#xD;
                 -  any investigational medications or investigational procedures&#xD;
  &#xD;
           29. Prior treatment with sonodynamic therapy&#xD;
  &#xD;
           30. Concurrent use of Optune device&#xD;
  &#xD;
           31. Concurrent use of supplements or medications with substantial antioxidant effects&#xD;
               (including sulfhydryl-containing medications such as captopril or supplements such as&#xD;
               N-acetylcysteine, or high doses of vitamins with antioxidant activity such as C or E)&#xD;
  &#xD;
           32. Known sensitivity to gadolinium&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Shayan Moosa, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>UVA</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Judith Beenhakker, M.S.</last_name>
      <phone>434-982-1856</phone>
      <email>jgb3p@uvahealth.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>University of Virginia</name>
        <address>
          <city>Charlottesville</city>
          <state>Virginia</state>
          <zip>22903</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Judith Beenhakker, MS</last_name>
        <phone>434-982-1856</phone>
        <email>jgb3p@uvahealth.org</email>
      </contact>
      <investigator>
        <last_name>Shayan Moosa, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Joseph Donahue, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 10, 2023</study_first_submitted>
    <study_first_submitted_qc>September 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 10, 2023</last_update_submitted>
    <last_update_submitted_qc>September 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>University of Virginia</investigator_affiliation>
      <investigator_full_name>Shayan Moosa, MD</investigator_full_name>
      <investigator_title>Assistant Professor of Neurosurgery</investigator_title>
    </responsible_party>
    <keyword>Sonodynamic Therapy</keyword>
    <keyword>Low-Intensity Focused Ultrasound (LIFU)</keyword>
    <keyword>Focused Ultrasound</keyword>
    <keyword>5-ALA</keyword>
    <keyword>Brain Cancer</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Glioblastoma</mesh_term>
      <mesh_term>Recurrence</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06039709
  org study id: HSR230064
  nct id: NCT06039709
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: Yes
  is unapproved device: Yes
  Patients diagnosed with glioblastoma (GBM) are faced with limited treatment options. This
        pilot study will evaluate the safety and feasibility of combining an investigational drug
        called 5-ALA with neuronavigation-guided low-intensity focused ultrasound (LIFU) for patients
        who have recurrent GBM. Focused ultrasound (FUS) can be used to non-invasively destroy tumor
        tissue while preserving normal tissue. When FUS is combined with 5-ALA, this combinatorial
        approach is called sonodynamic therapy (SDT), and this investigational therapy is being
        tested for its ability to cause damage to GBM cells. SDT will take place prior to surgery for
        recurrent GBM.
  The combination of 5-ALA (Gleolan) and LIFU is collectively known as sonodynamic therapy
        (SDT). SDT is an investigational therapy that will be administered 1-3 weeks before surgery
        for recurrent GBM. Researchers seek to determine the safety and feasibility of this therapy
        as well as measure its effectiveness to elicit tumor-cell death. All participants are
        expected to stay overnight in the hospital following administration of SDT to monitor for
        adverse events.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of adverse events
  time frame: From informed consent through 30 days after study intervention is complete
  description: Per NCI Common Terminology Criteria for Adverse Events v5.0
  measure: Severity of adverse events
  time frame: From informed consent through 30 days after study intervention is complete
  description: Per NCI Common Terminology Criteria for Adverse Events v5.0
  measure: Incidence of intracranial hemorrhage and/or worsening of edema
  time frame: From day after SDT (day 1) up to the time of surgery (day 7-day 21)
  description: On post-SDT MRIs
  measure: Extent of targeted tumor area receiving FUS
  time frame: Day 0
  description: Use of NaviFUS system to target a maximum of 50% of the tumor volume of one contiguous lesion
  measure: Ability to have participants undergo planned surgery without delay
  time frame: within 3 weeks following SDT
  description: A delay is defined as more than 3 weeks after SDT
  measure: Response of target tissue following SDT on imaging
  time frame: From day after SDT (day 1) up to 100 days after intervention is completed
  description: Via MRI w/ use of modified Response Assessment in Neuro-Oncology (RANO) criteria
  measure: Histologic tumor devitalization
  time frame: Day 7-Day 21
  description: Evaluating cell fate and cell death via histologic samples after GBM resection
  arm group label: Sonodynamic Therapy (5-ALA + LIFU)
  arm group type: Experimental
  description: Administration of SDT occurs 1-3 weeks prior to GBM resection
  intervention type: Combination Product
  intervention name: 5-ALA and Low-Intensity Focused Ultrasound (SDT)
  description: 5-ALA (20mg/kg orally) given ~6 hours prior to LIFU. Focused ultrasound will target a maximum of 50% of the tumor.
  arm group label: Sonodynamic Therapy (5-ALA + LIFU)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Shayan Moosa, MD
  role: Principal Investigator
  affiliation: UVA
  last name: Judith Beenhakker, M.S.
  phone: 434-982-1856
  email: jgb3p@uvahealth.org
  facility: 
  contact: 
  investigator: 
  investigator: 
  country: United States
  responsible party type: Sponsor-Investigator
  investigator affiliation: University of Virginia
  investigator full name: Shayan Moosa, MD
  investigator title: Assistant Professor of Neurosurgery
  mesh term: Glioblastoma
  mesh term: Recurrence
  sharing ipd: No