<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/NCT03841435</url>
  </required_header>
  <id_info>
    <org_study_id>2017-2183</org_study_id>
    <nct_id>NCT03841435</nct_id>
  </id_info>
  <brief_title>Hypofractionated Radiotherapy for Recurrent DIPG</brief_title>
  <official_title>Feasibility Study of Hypofractionated Radiotherapy in the Setting of Recurrent Diffuse Intrinsic Pontine Glioma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Cincinnati</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>
      This study evaluates the feasibility of hypofractionated radiotherapy (RT) in the palliative&#xD;
      treatment of recurrent diffuse intrinsic pontine glioma (DIPG). Participants will receive 15&#xD;
      Gy in 3 fractions as opposed to the standard 20 Gy in 10 fractions.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 31, 2018</start_date>
  <completion_date type="Actual">March 3, 2023</completion_date>
  <primary_completion_date type="Actual">March 3, 2023</primary_completion_date>
  <phase>N/A</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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Post Radiation Toxicity</measure>
    <time_frame>Through Study Completion, an average of 1 year</time_frame>
    <description>RTOG common toxicity criteria grade 0-5</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of Life score</measure>
    <time_frame>Pre-RT, 2 weeks, 1 month, 3 months and every 3 months there-after post RT</time_frame>
    <description>Patient reported quality of life via Pediatric Quality of Life Inventory Version 4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic Response</measure>
    <time_frame>1 month</time_frame>
    <description>Physician documented change of tumor from pre-RT MRI as compared to 1 month post-RT MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>Through Study Completion, an average of 1 year</time_frame>
    <description>Time to clinical, symptomatic or radiographic evidence of disease progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Through Study Completion, an average of 1 year</time_frame>
    <description>Time to patient death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Steroid Requirement</measure>
    <time_frame>Through Study Completion, an average of 1 year</time_frame>
    <description>Use of steroids post-RT</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Recurrent Diffuse Intrinsic Pontine Glioma</condition>
  <arm_group>
    <arm_group_label>Hypofractionated Radiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>15 Gy given in 3 fractions over 2 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Hypofractionated Radiotherapy</intervention_name>
    <description>Radiotherapy Treatment, totaling 15 Gy, will be given in 3 fractions over 2 weeks.</description>
    <arm_group_label>Hypofractionated Radiotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients must be ≤30 years of age&#xD;
&#xD;
          2. Patients must have a diagnosis of progressive DIPG.&#xD;
&#xD;
          3. Received prior IMRT based definitive radiotherapy to a dose of ≥54 Gy.&#xD;
&#xD;
          4. The patient and or parent/legal guardian must be physically and mentally capable of&#xD;
             signing the consent form of their own volition.&#xD;
&#xD;
          5. Steroids dosage must be unchanged for 5 days.&#xD;
&#xD;
          6. No Bevacizumab within 21 days (Half-life 11 days ~)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with incomplete medical records&#xD;
&#xD;
          2. Patients with prior history of reirradiation for DIPG&#xD;
&#xD;
          3. Life expectancy &lt; or equal to 1 month&#xD;
&#xD;
          4. Pregnant women&#xD;
&#xD;
          5. Age &gt;30&#xD;
&#xD;
          6. Prisoners&#xD;
&#xD;
          7. Concurrent systemic therapy at the time of reirradiation&#xD;
&#xD;
          8. Physically or mentally incapable of signing the consent form of their own volition&#xD;
&#xD;
          9. &lt; 6 mos time interval between completion of initial RT to start of reRT.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Luke E Pater, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol. 2013 Nov;15 Suppl 2(Suppl 2):ii1-56. doi: 10.1093/neuonc/not151. No abstract available. Erratum In: Neuro Oncol. 2014 May;16(5):760.</citation>
    <PMID>24137015</PMID>
  </reference>
  <reference>
    <citation>Vanan MI, Eisenstat DD. DIPG in Children - What Can We Learn from the Past? Front Oncol. 2015 Oct 21;5:237. doi: 10.3389/fonc.2015.00237. eCollection 2015.</citation>
    <PMID>26557503</PMID>
  </reference>
  <reference>
    <citation>Fangusaro J. Pediatric high-grade gliomas and diffuse intrinsic pontine gliomas. J Child Neurol. 2009 Nov;24(11):1409-17. doi: 10.1177/0883073809338960. Epub 2009 Jul 28.</citation>
    <PMID>19638636</PMID>
  </reference>
  <reference>
    <citation>Fontanilla HP, Pinnix CC, Ketonen LM, Woo SY, Vats TS, Rytting ME, Wolff JE, Mahajan A. Palliative reirradiation for progressive diffuse intrinsic pontine glioma. Am J Clin Oncol. 2012 Feb;35(1):51-7. doi: 10.1097/COC.0b013e318201a2b7.</citation>
    <PMID>21297433</PMID>
  </reference>
  <reference>
    <citation>Merchant TE, Boop FA, Kun LE, Sanford RA. A retrospective study of surgery and reirradiation for recurrent ependymoma. Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):87-97. doi: 10.1016/j.ijrobp.2007.09.037.</citation>
    <PMID>18406885</PMID>
  </reference>
  <reference>
    <citation>Liu AK, Foreman NK, Gaspar LE, Trinidad E, Handler MH. Maximally safe resection followed by hypofractionated re-irradiation for locally recurrent ependymoma in children. Pediatr Blood Cancer. 2009 Jul;52(7):804-7. doi: 10.1002/pbc.21982.</citation>
    <PMID>19260098</PMID>
  </reference>
  <reference>
    <citation>Bouffet E, Hawkins CE, Ballourah W, Taylor MD, Bartels UK, Schoenhoff N, Tsangaris E, Huang A, Kulkarni A, Mabbot DJ, Laperriere N, Tabori U. Survival benefit for pediatric patients with recurrent ependymoma treated with reirradiation. Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):1541-8. doi: 10.1016/j.ijrobp.2011.10.039. Epub 2012 Jan 13.</citation>
    <PMID>22245198</PMID>
  </reference>
  <reference>
    <citation>Iqbal MS, Lewis J. An overview of the management of adult ependymomas with emphasis on relapsed disease. Clin Oncol (R Coll Radiol). 2013 Dec;25(12):726-33. doi: 10.1016/j.clon.2013.07.009. Epub 2013 Aug 20.</citation>
    <PMID>23972764</PMID>
  </reference>
  <reference>
    <citation>Mayer R, Sminia P. Reirradiation tolerance of the human brain. Int J Radiat Oncol Biol Phys. 2008 Apr 1;70(5):1350-60. doi: 10.1016/j.ijrobp.2007.08.015. Epub 2007 Nov 26.</citation>
    <PMID>18037587</PMID>
  </reference>
  <reference>
    <citation>Massimino M, Biassoni V, Miceli R, Schiavello E, Warmuth-Metz M, Modena P, Casanova M, Pecori E, Giangaspero F, Antonelli M, Buttarelli FR, Potepan P, Pollo B, Nunziata R, Spreafico F, Podda M, Anichini A, Clerici CA, Sardi I, De Cecco L, Bode U, Bach F, Gandola L. Results of nimotuzumab and vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood. J Neurooncol. 2014 Jun;118(2):305-312. doi: 10.1007/s11060-014-1428-z. Epub 2014 Apr 3. Erratum In: J Neurooncol. 2018 May 16;:</citation>
    <PMID>24696052</PMID>
  </reference>
  <reference>
    <citation>Lassaletta A, Bartels U, Strother D, et al. Hg-57re-irradiation in patients with diffuse intrinsic pontine gliomas, an update on the canadian experience. Neuro-Oncology 2016;18:iii60-iii61.</citation>
  </reference>
  <reference>
    <citation>Freese C, Takiar V, Fouladi M, DeWire M, Breneman J, Pater L. Radiation and subsequent reirradiation outcomes in the treatment of diffuse intrinsic pontine glioma and a systematic review of the reirradiation literature. Pract Radiat Oncol. 2017 Mar-Apr;7(2):86-92. doi: 10.1016/j.prro.2016.11.005. Epub 2016 Nov 23.</citation>
    <PMID>28274399</PMID>
  </reference>
  <reference>
    <citation>Hoffman LM, Plimpton SR, Foreman NK, Stence NV, Hankinson TC, Handler MH, Hemenway MS, Vibhakar R, Liu AK. Fractionated stereotactic radiosurgery for recurrent ependymoma in children. J Neurooncol. 2014 Jan;116(1):107-11. doi: 10.1007/s11060-013-1259-3.</citation>
    <PMID>24078173</PMID>
  </reference>
  <reference>
    <citation>Mayo C, Yorke E, Merchant TE. Radiation associated brainstem injury. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S36-41. doi: 10.1016/j.ijrobp.2009.08.078.</citation>
    <PMID>20171516</PMID>
  </reference>
  <reference>
    <citation>Freeman CR, Krischer JP, Sanford RA, Cohen ME, Burger PC, del Carpio R, Halperin EC, Munoz L, Friedman HS, Kun LE. Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: a Pediatric Oncology Group study. Int J Radiat Oncol Biol Phys. 1993 Sep 30;27(2):197-206. doi: 10.1016/0360-3016(93)90228-n.</citation>
    <PMID>8407392</PMID>
  </reference>
  <reference>
    <citation>Packer RJ, Boyett JM, Zimmerman RA, Rorke LB, Kaplan AM, Albright AL, Selch MT, Finlay JL, Hammond GD, Wara WM. Hyperfractionated radiation therapy (72 Gy) for children with brain stem gliomas. A Childrens Cancer Group Phase I/II Trial. Cancer. 1993 Aug 15;72(4):1414-21. doi: 10.1002/1097-0142(19930815)72:43.0.co;2-c.</citation>
    <PMID>8339232</PMID>
  </reference>
  <reference>
    <citation>Packer RJ, Boyett JM, Zimmerman RA, Albright AL, Kaplan AM, Rorke LB, Selch MT, Cherlow JM, Finlay JL, Wara WM. Outcome of children with brain stem gliomas after treatment with 7800 cGy of hyperfractionated radiotherapy. A Childrens Cancer Group Phase I/II Trial. Cancer. 1994 Sep 15;74(6):1827-34. doi: 10.1002/1097-0142(19940915)74:63.0.co;2-q.</citation>
    <PMID>8082086</PMID>
  </reference>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>February 12, 2019</study_first_submitted>
  <study_first_submitted_qc>February 13, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Cincinnati</investigator_affiliation>
    <investigator_full_name>Luke Pater</investigator_full_name>
    <investigator_title>Associate Professor of Radiation Oncology, Mediacal Director, West Chester Hospital Radiotherapy</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioma</mesh_term>
    <mesh_term>Diffuse Intrinsic Pontine Glioma</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Individual participant data will be kept confidential and will not be shared with other researchers</ipd_description>
  </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/NCT03841435
org study id: 2017-2183
nct id: NCT03841435
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study evaluates the feasibility of hypofractionated radiotherapy (RT) in the palliative
      treatment of recurrent diffuse intrinsic pontine glioma (DIPG). Participants will receive 15
      Gy in 3 fractions as opposed to the standard 20 Gy in 10 fractions.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Post Radiation Toxicity
time frame: Through Study Completion, an average of 1 year
description: RTOG common toxicity criteria grade 0-5
measure: Change in Quality of Life score
time frame: Pre-RT, 2 weeks, 1 month, 3 months and every 3 months there-after post RT
description: Patient reported quality of life via Pediatric Quality of Life Inventory Version 4.0
measure: Radiographic Response
time frame: 1 month
description: Physician documented change of tumor from pre-RT MRI as compared to 1 month post-RT MRI
measure: Progression Free Survival
time frame: Through Study Completion, an average of 1 year
description: Time to clinical, symptomatic or radiographic evidence of disease progression
measure: Overall Survival
time frame: Through Study Completion, an average of 1 year
description: Time to patient death
measure: Steroid Requirement
time frame: Through Study Completion, an average of 1 year
description: Use of steroids post-RT
arm group label: Hypofractionated Radiotherapy
arm group type: Experimental
description: 15 Gy given in 3 fractions over 2 weeks
intervention type: Radiation
intervention name: Hypofractionated Radiotherapy
description: Radiotherapy Treatment, totaling 15 Gy, will be given in 3 fractions over 2 weeks.
arm group label: Hypofractionated Radiotherapy
criteria: 
gender: All
minimum age: N/A
maximum age: 30 Years
healthy volunteers: No
last name: Luke E Pater, MD
role: Principal Investigator
affiliation: University of Cincinnati
facility: 
country: United States
citation: Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol. 2013 Nov;15 Suppl 2(Suppl 2):ii1-56. doi: 10.1093/neuonc/not151. No abstract available. Erratum In: Neuro Oncol. 2014 May;16(5):760.
PMID: 24137015
citation: Vanan MI, Eisenstat DD. DIPG in Children - What Can We Learn from the Past? Front Oncol. 2015 Oct 21;5:237. doi: 10.3389/fonc.2015.00237. eCollection 2015.
PMID: 26557503
citation: Fangusaro J. Pediatric high-grade gliomas and diffuse intrinsic pontine gliomas. J Child Neurol. 2009 Nov;24(11):1409-17. doi: 10.1177/0883073809338960. Epub 2009 Jul 28.
PMID: 19638636
citation: Fontanilla HP, Pinnix CC, Ketonen LM, Woo SY, Vats TS, Rytting ME, Wolff JE, Mahajan A. Palliative reirradiation for progressive diffuse intrinsic pontine glioma. Am J Clin Oncol. 2012 Feb;35(1):51-7. doi: 10.1097/COC.0b013e318201a2b7.
PMID: 21297433
citation: Merchant TE, Boop FA, Kun LE, Sanford RA. A retrospective study of surgery and reirradiation for recurrent ependymoma. Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):87-97. doi: 10.1016/j.ijrobp.2007.09.037.
PMID: 18406885
citation: Liu AK, Foreman NK, Gaspar LE, Trinidad E, Handler MH. Maximally safe resection followed by hypofractionated re-irradiation for locally recurrent ependymoma in children. Pediatr Blood Cancer. 2009 Jul;52(7):804-7. doi: 10.1002/pbc.21982.
PMID: 19260098
citation: Bouffet E, Hawkins CE, Ballourah W, Taylor MD, Bartels UK, Schoenhoff N, Tsangaris E, Huang A, Kulkarni A, Mabbot DJ, Laperriere N, Tabori U. Survival benefit for pediatric patients with recurrent ependymoma treated with reirradiation. Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):1541-8. doi: 10.1016/j.ijrobp.2011.10.039. Epub 2012 Jan 13.
PMID: 22245198
citation: Iqbal MS, Lewis J. An overview of the management of adult ependymomas with emphasis on relapsed disease. Clin Oncol (R Coll Radiol). 2013 Dec;25(12):726-33. doi: 10.1016/j.clon.2013.07.009. Epub 2013 Aug 20.
PMID: 23972764
citation: Mayer R, Sminia P. Reirradiation tolerance of the human brain. Int J Radiat Oncol Biol Phys. 2008 Apr 1;70(5):1350-60. doi: 10.1016/j.ijrobp.2007.08.015. Epub 2007 Nov 26.
PMID: 18037587
citation: Massimino M, Biassoni V, Miceli R, Schiavello E, Warmuth-Metz M, Modena P, Casanova M, Pecori E, Giangaspero F, Antonelli M, Buttarelli FR, Potepan P, Pollo B, Nunziata R, Spreafico F, Podda M, Anichini A, Clerici CA, Sardi I, De Cecco L, Bode U, Bach F, Gandola L. Results of nimotuzumab and vinorelbine, radiation and re-irradiation for diffuse pontine glioma in childhood. J Neurooncol. 2014 Jun;118(2):305-312. doi: 10.1007/s11060-014-1428-z. Epub 2014 Apr 3. Erratum In: J Neurooncol. 2018 May 16;:
PMID: 24696052
citation: Lassaletta A, Bartels U, Strother D, et al. Hg-57re-irradiation in patients with diffuse intrinsic pontine gliomas, an update on the canadian experience. Neuro-Oncology 2016;18:iii60-iii61.
citation: Freese C, Takiar V, Fouladi M, DeWire M, Breneman J, Pater L. Radiation and subsequent reirradiation outcomes in the treatment of diffuse intrinsic pontine glioma and a systematic review of the reirradiation literature. Pract Radiat Oncol. 2017 Mar-Apr;7(2):86-92. doi: 10.1016/j.prro.2016.11.005. Epub 2016 Nov 23.
PMID: 28274399
citation: Hoffman LM, Plimpton SR, Foreman NK, Stence NV, Hankinson TC, Handler MH, Hemenway MS, Vibhakar R, Liu AK. Fractionated stereotactic radiosurgery for recurrent ependymoma in children. J Neurooncol. 2014 Jan;116(1):107-11. doi: 10.1007/s11060-013-1259-3.
PMID: 24078173
citation: Mayo C, Yorke E, Merchant TE. Radiation associated brainstem injury. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S36-41. doi: 10.1016/j.ijrobp.2009.08.078.
PMID: 20171516
citation: Freeman CR, Krischer JP, Sanford RA, Cohen ME, Burger PC, del Carpio R, Halperin EC, Munoz L, Friedman HS, Kun LE. Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: a Pediatric Oncology Group study. Int J Radiat Oncol Biol Phys. 1993 Sep 30;27(2):197-206. doi: 10.1016/0360-3016(93)90228-n.
PMID: 8407392
citation: Packer RJ, Boyett JM, Zimmerman RA, Rorke LB, Kaplan AM, Albright AL, Selch MT, Finlay JL, Hammond GD, Wara WM. Hyperfractionated radiation therapy (72 Gy) for children with brain stem gliomas. A Childrens Cancer Group Phase I/II Trial. Cancer. 1993 Aug 15;72(4):1414-21. doi: 10.1002/1097-0142(19930815)72:43.0.co;2-c.
PMID: 8339232
citation: Packer RJ, Boyett JM, Zimmerman RA, Albright AL, Kaplan AM, Rorke LB, Selch MT, Cherlow JM, Finlay JL, Wara WM. Outcome of children with brain stem gliomas after treatment with 7800 cGy of hyperfractionated radiotherapy. A Childrens Cancer Group Phase I/II Trial. Cancer. 1994 Sep 15;74(6):1827-34. doi: 10.1002/1097-0142(19940915)74:63.0.co;2-q.
PMID: 8082086
responsible party type: Principal Investigator
investigator affiliation: University of Cincinnati
investigator full name: Luke Pater
investigator title: Associate Professor of Radiation Oncology, Mediacal Director, West Chester Hospital Radiotherapy
mesh term: Glioma
mesh term: Diffuse Intrinsic Pontine Glioma
mesh term: Recurrence
sharing ipd: No
ipd description: Individual participant data will be kept confidential and will not be shared with other researchers