<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/NCT01682746</url>
  </required_header>
  <id_info>
    <org_study_id>163588-1</org_study_id>
    <nct_id>NCT01682746</nct_id>
  </id_info>
  <brief_title>Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors</brief_title>
  <official_title>Photodynamic Therapy (PDT) for Poor Prognosis Recurrent/Refractory Malignant Brain Tumors - A Phase I Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Harry T Whelan, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pinnacle Biologics Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical College of Wisconsin</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this proposal is to evaluate a new Photodynamic Therapy (PDT) modification which&#xD;
      could revolutionize the treatment of brain tumors in children and adults. There are currently&#xD;
      few cases published involving the use of PDT in infratentorial (in the posterior fossa) brain&#xD;
      tumors in general and specifically those occurring in children. The investigators propose to&#xD;
      test a technique, for the first time in the U.S., that demonstrated in Australian adult&#xD;
      glioblastoma patients dramatic long-term, survival rates of 57% (anaplastic astrocytoma) and&#xD;
      37% (glioblastoma multiforme). These results are unprecedented in any other treatment&#xD;
      protocol.&#xD;
&#xD;
      Photodynamic therapy (PDT) is a paradigm shift in the treatment of tumors from the&#xD;
      traditional resection and systemic chemotherapy methods. The principle behind photodynamic&#xD;
      therapy is light-mediated activation of a photosensitizer that is selectively accumulated in&#xD;
      the target tissue, causing tumor cell destruction through singlet oxygen production.&#xD;
      Therefore, the photosensitizer is considered to be the first critical element in PDT&#xD;
      procedures, and the activation procedure is the second step. The methodology used in this&#xD;
      proposal utilizes more intensive laser light and larger Photofrin photosensitizer doses than&#xD;
      prior PDT protocols in the U.S. for brain tumor patients. The PDT will consist of&#xD;
      photoillumination at 630 nm beginning at the center of the tumor resection cavity, and&#xD;
      delivering a total energy of 240 J cm-2. The investigators feel that the light should&#xD;
      penetrate far enough into the tissue to reach migrating tumor cells, and destroy these cells&#xD;
      without harming the healthy cells in which they are dispersed.&#xD;
&#xD;
      The investigators will be testing the hypothesis that pediatric subjects with&#xD;
      progressive/recurrent malignant brain tumors undergoing PDT with increased doses of&#xD;
      Photofrin® and light energy than were used in our previous clinical study will show better&#xD;
      progression free survival (PFS) and overall survival (OS) outcomes. PDT will also be&#xD;
      effective against infratentorial tumors. The specific aims include determining the maximum&#xD;
      tolerable dose (MTD) of Photofrin in children and looking for preliminary effectiveness&#xD;
      trends.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">June 29, 2018</completion_date>
  <primary_completion_date type="Actual">June 29, 2018</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>Maximum tolerable dose (MTD) of Photofrin® in pediatric subjects</measure>
    <time_frame>One to four weeks from PDT</time_frame>
    <description>MTD is defined as the Photofrin® dose that precedes the dose level used with a subgroup of subjects that exhibits a greater than 33% DLT occurrence.&#xD;
DLT is defined as any of the following events with reasonable possibility to be attributable to the experimental intervention:&#xD;
Neurotoxicity: defined as a decline in neurological function manifest within 1 week of PDT and persistent to 4 weeks post-PDT. Adverse events of neurologic function of grade 4, or a level change from grade 1 to grade 3, within this period will constitute neurotoxicity for this study. The CTCAE V4.02 will be used.&#xD;
Photosensitivity: defined as a photosensitivity adverse event (CTCAE category dermatology/skin) of grade 4 occurring within the same period.&#xD;
Ocular sensitivity: Photofrin®-induced ocular sensitivity is defined as a photophobia adverse event (CTCAE category ocular/visual) of grade 4 within the same period.&#xD;
Any other toxicity of CTCAE grade 4 or higher within the same period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Brain tumor response</measure>
    <time_frame>Response ocurring within 3 years after PDT</time_frame>
    <description>To preliminarily define the antitumor activity of Photofrin and laser light activation within the confines of a Phase 1 Study. We will follow progression free survival and overall survival for 3 years post PDT treatment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Brain Tumor, Recurrent</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Photofrin (porfimer sodium) photodynamic therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Photofrin (porfimer sodium) &amp; photodynamic therapy.</intervention_name>
    <description>Intravenous (IV) Photofrin&#xD;
This is a dose escalation study. Patients will receive Photofrin via an IV infusion approximately 24 hours prior to their tumor resection surgery and Photodynamic Therapy (PDT). Patients will be light sensitive immediately upon receiving the Photofrin and must observe photosensitivity &amp; light precautions for a minimum of 30 days after the infusion.&#xD;
Photodynamic Therapy (PDT)&#xD;
After tumor resection, an optical fiber will be placed in the approximate center of the surgical cavity. Intralipid will be infused into the open tumor cavity while PDT is performed. The Intralipid will diffuse the light and ensure uniform delivery. Photoactivation of Photofrin is controlled by the total light dose delivered over the treatment time.</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        1. Age: ≥ 6 months and &lt; 18 years&#xD;
&#xD;
          2. Disease: Patients with relapsed or refractory brain tumors are eligible. Patients must&#xD;
             have had histologic verification of malignancy at original diagnosis or relapse.&#xD;
             Tumors can be either supratentorial or infratentorial (posterior fossa) in location.&#xD;
&#xD;
          3. Disease Status: Patients must have potentially resectable disease.&#xD;
&#xD;
          4. Therapeutic Options: Patients' current disease state must be one for which there is no&#xD;
             known curative therapy or therapy proven to prolong survival with an acceptable&#xD;
             quality of life.&#xD;
&#xD;
          5. Performance Level: Karnofsky 50% or greater for patients &gt; 16 years of age and Lansky&#xD;
             50 or greater for patients &lt; 16 years of age. Note: Neurologic deficits in patients&#xD;
             with CNS tumors must have been relatively stable for at least 7 days prior to study&#xD;
             enrollment. Patients who are unable to walk because of paralysis, but who are up in a&#xD;
             wheelchair, will be considered ambulatory for the purpose of assessing the performance&#xD;
             score.&#xD;
&#xD;
          6. Predictable Life Expectancy: &gt; 8 weeks&#xD;
&#xD;
          7. Prior Therapy: Patients must have fully recovered from the acute toxic effects of all&#xD;
             prior anti-cancer chemotherapy. At least 3 weeks from previous chemotherapy and 4&#xD;
             weeks from prior radiation therapy&#xD;
&#xD;
          8. Organ Function:&#xD;
&#xD;
             Adequate bone marrow function&#xD;
&#xD;
             Absolute neutrophil count ≥ 1,000&#xD;
&#xD;
             Platelet count ≥ 100,000 (may transfuse to meet requirement)&#xD;
&#xD;
             Adequate renal function&#xD;
&#xD;
             Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 OR&#xD;
&#xD;
             A serum creatinine within normal range based on age/gender&#xD;
&#xD;
             Adequate liver function Bilirubin (direct) ≤ 3X upper limit of normal (ULN) for age&#xD;
&#xD;
             SGPT (ALT) ≤ 10X ULN&#xD;
&#xD;
             For the purpose of this study, the ULN for SGPT is 45 U/L&#xD;
&#xD;
             Serum albumin ≥ 2 g/dL&#xD;
&#xD;
             Adequate coagulation&#xD;
&#xD;
             PT and INR ≤ 2X ULN for age&#xD;
&#xD;
          9. Central Nervous System Function: Patients with seizure disorder may be enrolled if&#xD;
             receiving non- enzyme inducing anticonvulsants and well controlled.&#xD;
&#xD;
         10. Informed Consent: All patients and/or their parents or legally authorized&#xD;
             representatives must sign a written informed consent. Assent, when appropriate, will&#xD;
             be obtained according to institutional guidelines.&#xD;
&#xD;
         11. Archival tumor tissue slides from initial diagnosis should be reviewed by CHW&#xD;
             institutional pathologists prior to study enrollment whenever possible.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Disseminated disease (metastatic disease)&#xD;
&#xD;
          2. Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on&#xD;
             this study, as risks of fetal and teratogenic adverse effects of Photofrin® are not&#xD;
             known.&#xD;
&#xD;
          3. Other concurrent tumor therapy&#xD;
&#xD;
          4. Subjects with porphyria&#xD;
&#xD;
          5. Subjects taking potentially photosensitizing drugs&#xD;
&#xD;
          6. The presence of adverse events of neurologic function, photosensitivity, or&#xD;
             photophobia Grade 4 or higher (CTCAE Version 4.0)&#xD;
&#xD;
          7. Allergy to eggs, soybean oil, or safflower oil (due to potential allergy against&#xD;
             intralipids)&#xD;
&#xD;
          8. Patients who in the opinion of the investigator may not be able to comply with the&#xD;
             safety monitoring requirements of the study are not eligible.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Harry T Whelan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical College of Wisconsin</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jeff Knipstein, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical College of Wisconsin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital of Wisconsin</name>
      <address>
        <city>Wauwatosa</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>September 5, 2012</study_first_submitted>
  <study_first_submitted_qc>September 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <last_update_submitted>February 21, 2019</last_update_submitted>
  <last_update_submitted_qc>February 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Medical College of Wisconsin</investigator_affiliation>
    <investigator_full_name>Harry T Whelan, MD</investigator_full_name>
    <investigator_title>Bleser Professor of Neurology</investigator_title>
  </responsible_party>
  <keyword>Brain Tumor</keyword>
  <keyword>Photodynamic Therapy</keyword>
  <keyword>Photochemotherapy</keyword>
  <keyword>Astrocytoma</keyword>
  <keyword>Pilocytic Astrocytoma</keyword>
  <keyword>Low grade Astrocytoma</keyword>
  <keyword>Anaplastic Astrocytoma</keyword>
  <keyword>Glioblastoma</keyword>
  <keyword>GBM</keyword>
  <keyword>Chordoma</keyword>
  <keyword>Germinoma</keyword>
  <keyword>Germ Cell Tumor</keyword>
  <keyword>Non-germinaoma</keyword>
  <keyword>CNS Lymphoma</keyword>
  <keyword>Craniopharyngioma</keyword>
  <keyword>Brain Stem Glioma</keyword>
  <keyword>Ependymoma</keyword>
  <keyword>Mixed Glioma</keyword>
  <keyword>Optic Nerve Glioma</keyword>
  <keyword>Subependymoma</keyword>
  <keyword>Medulloblastoma</keyword>
  <keyword>Meningioma</keyword>
  <keyword>Metastatic Brain Tumors</keyword>
  <keyword>Oligodendroglioma</keyword>
  <keyword>Pituitary Tumors</keyword>
  <keyword>Primitive Neuroectodermal</keyword>
  <keyword>PNET</keyword>
  <keyword>Desmoplastic Neuroepithelial Tumor</keyword>
  <keyword>DNET</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dihematoporphyrin Ether</mesh_term>
    <mesh_term>Trioxsalen</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/NCT01682746
org study id: 163588-1
nct id: NCT01682746
lead sponsor: 
collaborator: 
has dmc: Yes
The goal of this proposal is to evaluate a new Photodynamic Therapy (PDT) modification which
      could revolutionize the treatment of brain tumors in children and adults. There are currently
      few cases published involving the use of PDT in infratentorial (in the posterior fossa) brain
      tumors in general and specifically those occurring in children. The investigators propose to
      test a technique, for the first time in the U.S., that demonstrated in Australian adult
      glioblastoma patients dramatic long-term, survival rates of 57% (anaplastic astrocytoma) and
      37% (glioblastoma multiforme). These results are unprecedented in any other treatment
      protocol.

      Photodynamic therapy (PDT) is a paradigm shift in the treatment of tumors from the
      traditional resection and systemic chemotherapy methods. The principle behind photodynamic
      therapy is light-mediated activation of a photosensitizer that is selectively accumulated in
      the target tissue, causing tumor cell destruction through singlet oxygen production.
      Therefore, the photosensitizer is considered to be the first critical element in PDT
      procedures, and the activation procedure is the second step. The methodology used in this
      proposal utilizes more intensive laser light and larger Photofrin photosensitizer doses than
      prior PDT protocols in the U.S. for brain tumor patients. The PDT will consist of
      photoillumination at 630 nm beginning at the center of the tumor resection cavity, and
      delivering a total energy of 240 J cm-2. The investigators feel that the light should
      penetrate far enough into the tissue to reach migrating tumor cells, and destroy these cells
      without harming the healthy cells in which they are dispersed.

      The investigators will be testing the hypothesis that pediatric subjects with
      progressive/recurrent malignant brain tumors undergoing PDT with increased doses of
      Photofrin® and light energy than were used in our previous clinical study will show better
      progression free survival (PFS) and overall survival (OS) outcomes. PDT will also be
      effective against infratentorial tumors. The specific aims include determining the maximum
      tolerable dose (MTD) of Photofrin in children and looking for preliminary effectiveness
      trends.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerable dose (MTD) of Photofrin® in pediatric subjects
time frame: One to four weeks from PDT
description: MTD is defined as the Photofrin® dose that precedes the dose level used with a subgroup of subjects that exhibits a greater than 33% DLT occurrence.
DLT is defined as any of the following events with reasonable possibility to be attributable to the experimental intervention:
Neurotoxicity: defined as a decline in neurological function manifest within 1 week of PDT and persistent to 4 weeks post-PDT. Adverse events of neurologic function of grade 4, or a level change from grade 1 to grade 3, within this period will constitute neurotoxicity for this study. The CTCAE V4.02 will be used.
Photosensitivity: defined as a photosensitivity adverse event (CTCAE category dermatology/skin) of grade 4 occurring within the same period.
Ocular sensitivity: Photofrin®-induced ocular sensitivity is defined as a photophobia adverse event (CTCAE category ocular/visual) of grade 4 within the same period.
Any other toxicity of CTCAE grade 4 or higher within the same period.
measure: Brain tumor response
time frame: Response ocurring within 3 years after PDT
description: To preliminarily define the antitumor activity of Photofrin and laser light activation within the confines of a Phase 1 Study. We will follow progression free survival and overall survival for 3 years post PDT treatment.
arm group label: Treatment
arm group type: Experimental
description: Photofrin (porfimer sodium) photodynamic therapy.
intervention type: Drug
intervention name: Photofrin (porfimer sodium) & photodynamic therapy.
description: Intravenous (IV) Photofrin
This is a dose escalation study. Patients will receive Photofrin via an IV infusion approximately 24 hours prior to their tumor resection surgery and Photodynamic Therapy (PDT). Patients will be light sensitive immediately upon receiving the Photofrin and must observe photosensitivity & light precautions for a minimum of 30 days after the infusion.
Photodynamic Therapy (PDT)
After tumor resection, an optical fiber will be placed in the approximate center of the surgical cavity. Intralipid will be infused into the open tumor cavity while PDT is performed. The Intralipid will diffuse the light and ensure uniform delivery. Photoactivation of Photofrin is controlled by the total light dose delivered over the treatment time.
arm group label: Treatment
criteria: 
gender: All
minimum age: 6 Months
maximum age: 18 Years
healthy volunteers: No
last name: Harry T Whelan, MD
role: Principal Investigator
affiliation: Medical College of Wisconsin
last name: Jeff Knipstein, MD
role: Principal Investigator
affiliation: Medical College of Wisconsin
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Medical College of Wisconsin
investigator full name: Harry T Whelan, MD
investigator title: Bleser Professor of Neurology
mesh term: Brain Neoplasms
mesh term: Recurrence
mesh term: Dihematoporphyrin Ether
mesh term: Trioxsalen