<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/NCT02227576</url>
  </required_header>
  <id_info>
    <org_study_id>2011_29</org_study_id>
    <secondary_id>2012-001751-38</secondary_id>
    <nct_id>NCT02227576</nct_id>
  </id_info>
  <brief_title>Prevention of Thrombocytopenia in Glioblastoma Patients</brief_title>
  <acronym>PLATUM</acronym>
  <official_title>Secondary Prophylaxis Use of Romiplostim for the Prevention of Thrombocytopenia Induced by Temozolomide in Newly Diagnosed Glioblastoma Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Lille</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chemotherapy used in the treatment of primitive tumors of the central nervous system has a&#xD;
      particularly important platelet toxicity compared to chemotherapy used for treatment of other&#xD;
      tumors. Chemotherapy postponed for toxicity is often due to thrombocytopenia (TP). The TP&#xD;
      and/or the other anomalies of coagulation, which can be spontaneous (Rogers, 2004) or induced&#xD;
      (Gerber, 2006) can have dramatic consequences:&#xD;
&#xD;
        -  specifically neurological (intratumoral bleeding with particularly important&#xD;
           neovascularization) with a functional aggravation and sometimes involvement of vital&#xD;
           prognosis,&#xD;
&#xD;
        -  digestive (Garcia-Rodiguez, 2001) in patients receiving long term treatment with&#xD;
           corticoids (potential gastric toxicity).&#xD;
&#xD;
      The encouraging results from the EORTC/NCIC trial by Stupp (median survival among patients&#xD;
      with newly diagnosed glioblastoma is 14.6 months with an estimated 5-year survival of 9, 8%),&#xD;
      has changed the standard of care of these patients (Stupp et al., 2009). Patients with newly&#xD;
      diagnosed, histologically confirmed glioblastoma receive radiotherapy (2 Gy given 5 days per&#xD;
      week for 6 weeks, for a total of 60 Gy) plus continuous daily Temozolomide (75 mg per square&#xD;
      meter of body-surface area per day, 7 days per week from the first to the last day of&#xD;
      radiotherapy), followed by six cycles of adjuvant Temozolomide (TMZ) (150 to 200 mg per&#xD;
      square meter for 5 days during each 28-day cycle). The Stupp regimen is currently the&#xD;
      treatment of reference for glioblastoma and is used as a basis in various clinical studies&#xD;
      with new agents.&#xD;
&#xD;
      This study aims to evaluate Romiplostim for the treatment of TP secondary to initial TMZ&#xD;
      chemotherapy of glioblastomas.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study halted for efficacy following the results of the interim analysis provided for in the&#xD;
    protocol on 20 patients.&#xD;
  </why_stopped>
  <start_date type="Actual">July 10, 2014</start_date>
  <completion_date type="Actual">December 14, 2017</completion_date>
  <primary_completion_date type="Actual">December 14, 2017</primary_completion_date>
  <phase>Phase 2</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>Proportion of patients receiving 100% of the planned TMZ dosage in the whole Stupp protocol. The primary endpoint will consider dose reduction and dose delay.</measure>
    <time_frame>one year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of serious adverse events according to CTCAE 4.0 criteria.</measure>
    <time_frame>one year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of delayed chemotherapy cycles and the incidence of chemotherapy cycles with dose reduction due to severe TP</measure>
    <time_frame>one year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and percentage of patients with TP of grade 3 or grade 4 after receiving Romiplostim.</measure>
    <time_frame>One year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and percentage of patients receiving platelets transfusion for TP</measure>
    <time_frame>one year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and type of adverse events linked to TP episodes during Romiplostim and Temozolomide combined treatment.</measure>
    <time_frame>one year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6 months Progression Free Survival:</measure>
    <time_frame>one year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Thrombocytopenia</condition>
  <condition>Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Romiplostim</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Romiplostim lyophilized formulation is a white, solide cake that is reconstituted with sterile water for injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Romiplostim</intervention_name>
    <arm_group_label>Romiplostim</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological proof of newly diagnosed glioblastoma,&#xD;
&#xD;
          -  Age: 18 and older,&#xD;
&#xD;
          -  Information to patient and signed consent form,&#xD;
&#xD;
          -  Indication for a &quot; Stupp &quot; protocol (cerebral focal radiotherapy and concomitant TMZ&#xD;
             followed by adjuvant TMZ - 6 cycles),&#xD;
&#xD;
          -  Patient with grade 3 or 4 TP during Temozolomide chemotherapy, regardless of when the&#xD;
             onset of TP was: after completion of concomitant RT/CT, before adjuvant CT or during&#xD;
             adjuvant CT and only if a minimum of 2 cycles are still planned,&#xD;
&#xD;
          -  Normal initial platelets count (&gt; 100 000/mm3) before the start of Temozolomide during&#xD;
             the RT/CT concomitant phase,&#xD;
&#xD;
          -  Adequate haematological, renal, hepatic function at the time of inclusion visit,&#xD;
&#xD;
          -  ECOG PS 0-2 (patients unable to walk because of a paralysis and who are up in a wheel&#xD;
             chair will be considered as ambulatory for the evaluation of the ECOG performance&#xD;
             status),&#xD;
&#xD;
          -  Life expectancy &gt; 2 months,&#xD;
&#xD;
          -  Patients covered by the French Health Insurance System,&#xD;
&#xD;
          -  Negative pregnancy test at the time of inclusion visit,&#xD;
&#xD;
          -  If required, effective contraception respecting criteria of CPMP/ICH/286/95 (such as&#xD;
             implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or&#xD;
             vasectomised partner).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant radiotherapy (Romiplostim will be started after the completion of the&#xD;
             RT/CT concomitant phase),&#xD;
&#xD;
          -  Other malignancies (prior hx malignancies),&#xD;
&#xD;
          -  Any anterior systemic chemotherapy,&#xD;
&#xD;
          -  Any known coagulation disease or known haematological disease even if resolved. Known&#xD;
             hypercoagulate state (e.g., factor V Leiden, protein C defiency, protein S deficiency,&#xD;
             PT 20201, antiphospholipid antibody syndrome…),&#xD;
&#xD;
          -  Prior Romiplostim exposure or prior exposure to other TPO mimetics,&#xD;
&#xD;
          -  History of thromboembolic disease &lt; 6 months. Treatment with anticoagulant such as&#xD;
             Heparin or antivitamin K (LMWH as prophylactic treatment is authorized),&#xD;
&#xD;
          -  Any other hemato-toxicity (anemia, neutropenia) requiring EPO or GCSF,&#xD;
&#xD;
          -  Other causes of Temozolomide interruption (non haematological toxicities),&#xD;
&#xD;
          -  Known hypersensitivity to any E-coli derived product,&#xD;
&#xD;
          -  Participation to any other study during the last 30 days,&#xD;
&#xD;
          -  Refusal to give written informed consent,&#xD;
&#xD;
          -  Pregnancy or nursing,&#xD;
&#xD;
          -  For all men and women of childbearing potential: Refusal or inability to use effective&#xD;
             means of contraception,&#xD;
&#xD;
          -  Any psychological, familial, sociological or geographical condition potentially&#xD;
             hampering compliance with the study protocol and follow-up schedule; those conditions&#xD;
             should be discussed with the patient before registration in the trial,&#xD;
&#xD;
          -  Persons protected by a legal regime (guardianship, trusteeship),&#xD;
&#xD;
          -  Patients in emergency situations,&#xD;
&#xD;
          -  Patients kept in detention.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Emilie Le Rhun, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHRU Lille</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHRU de Lille, Hôpital Roger Salengro,Clinique de Neurochirurgie</name>
      <address>
        <city>Lille</city>
        <zip>59037 Cedex</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Neurologique Pierre Wertheimer, Lyon,</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AP-HM,Hôpital La Timone, AP-HM, Marseille</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AH-HP, Hôpital Pitié-Salpêtrière, Service de Neurologie 2</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Armstrong TS, Cao Y, Scheurer ME, Vera-Bolanos E, Manning R, Okcu MF, Bondy M, Zhou R, Gilbert MR. Risk analysis of severe myelotoxicity with temozolomide: the effects of clinical and genetic factors. Neuro Oncol. 2009 Dec;11(6):825-32. doi: 10.1215/15228517-2008-120.</citation>
    <PMID>19179423</PMID>
  </reference>
  <reference>
    <citation>Gerber DE, Grossman SA, Zeltzman M, Parisi MA, Kleinberg L. The impact of thrombocytopenia from temozolomide and radiation in newly diagnosed adults with high-grade gliomas. Neuro Oncol. 2007 Jan;9(1):47-52. doi: 10.1215/15228517-2006-024. Epub 2006 Nov 15.</citation>
    <PMID>17108062</PMID>
  </reference>
  <reference>
    <citation>George JN, Raskob GE, Shah SR, Rizvi MA, Hamilton SA, Osborne S, Vondracek T. Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med. 1998 Dec 1;129(11):886-90. doi: 10.7326/0003-4819-129-11_part_1-199812010-00009.</citation>
    <PMID>9867731</PMID>
  </reference>
  <reference>
    <citation>Kuter DJ, Rummel M, Boccia R, Macik BG, Pabinger I, Selleslag D, Rodeghiero F, Chong BH, Wang X, Berger DP. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010 Nov 11;363(20):1889-99. doi: 10.1056/NEJMoa1002625.</citation>
    <PMID>21067381</PMID>
  </reference>
  <reference>
    <citation>Molineux G. The development of romiplostim for patients with immune thrombocytopenia. Ann N Y Acad Sci. 2011 Mar;1222:55-63. doi: 10.1111/j.1749-6632.2011.05975.x.</citation>
    <PMID>21434943</PMID>
  </reference>
  <reference>
    <citation>Sure D, Dunn I, Norden A, Anderson WS. Intracerebral hemorrhage secondary to thrombocytopenia in a patient treated with temozolomide. Clin Neurol Neurosurg. 2010 Oct;112(8):741-2. doi: 10.1016/j.clineuro.2010.04.005.</citation>
    <PMID>20434832</PMID>
  </reference>
  <reference>
    <citation>Mutter N, Stupp R. Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev Anticancer Ther. 2006 Aug;6(8):1187-204. doi: 10.1586/14737140.6.8.1187.</citation>
    <PMID>16925485</PMID>
  </reference>
  <reference>
    <citation>Oh J, Kutas GJ, Davey P, Morrison M, Perry JR. Aplastic anemia with concurrent temozolomide treatment in a patient with glioblastoma multiforme. Curr Oncol. 2010 Aug;17(4):124-6. doi: 10.3747/co.v17i4.526.</citation>
    <PMID>20697524</PMID>
  </reference>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <last_update_submitted>April 23, 2018</last_update_submitted>
  <last_update_submitted_qc>April 23, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>glioblastoma, thrombocytopenia, temozolomide, chemotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
    <mesh_term>Thrombocytopenia</mesh_term>
  </condition_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/NCT02227576
org study id: 2011_29
secondary id: 2012-001751-38
nct id: NCT02227576
lead sponsor: 
has dmc: Yes
Chemotherapy used in the treatment of primitive tumors of the central nervous system has a
      particularly important platelet toxicity compared to chemotherapy used for treatment of other
      tumors. Chemotherapy postponed for toxicity is often due to thrombocytopenia (TP). The TP
      and/or the other anomalies of coagulation, which can be spontaneous (Rogers, 2004) or induced
      (Gerber, 2006) can have dramatic consequences:

        -  specifically neurological (intratumoral bleeding with particularly important
           neovascularization) with a functional aggravation and sometimes involvement of vital
           prognosis,

        -  digestive (Garcia-Rodiguez, 2001) in patients receiving long term treatment with
           corticoids (potential gastric toxicity).

      The encouraging results from the EORTC/NCIC trial by Stupp (median survival among patients
      with newly diagnosed glioblastoma is 14.6 months with an estimated 5-year survival of 9, 8%),
      has changed the standard of care of these patients (Stupp et al., 2009). Patients with newly
      diagnosed, histologically confirmed glioblastoma receive radiotherapy (2 Gy given 5 days per
      week for 6 weeks, for a total of 60 Gy) plus continuous daily Temozolomide (75 mg per square
      meter of body-surface area per day, 7 days per week from the first to the last day of
      radiotherapy), followed by six cycles of adjuvant Temozolomide (TMZ) (150 to 200 mg per
      square meter for 5 days during each 28-day cycle). The Stupp regimen is currently the
      treatment of reference for glioblastoma and is used as a basis in various clinical studies
      with new agents.

      This study aims to evaluate Romiplostim for the treatment of TP secondary to initial TMZ
      chemotherapy of glioblastomas.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients receiving 100% of the planned TMZ dosage in the whole Stupp protocol. The primary endpoint will consider dose reduction and dose delay.
time frame: one year
measure: Incidence of serious adverse events according to CTCAE 4.0 criteria.
time frame: one year
measure: Incidence of delayed chemotherapy cycles and the incidence of chemotherapy cycles with dose reduction due to severe TP
time frame: one year
measure: Number and percentage of patients with TP of grade 3 or grade 4 after receiving Romiplostim.
time frame: One year
measure: Number and percentage of patients receiving platelets transfusion for TP
time frame: one year
measure: Incidence and type of adverse events linked to TP episodes during Romiplostim and Temozolomide combined treatment.
time frame: one year
measure: 6 months Progression Free Survival:
time frame: one year
arm group label: Romiplostim
arm group type: Experimental
description: Romiplostim lyophilized formulation is a white, solide cake that is reconstituted with sterile water for injection.
intervention type: Drug
intervention name: Romiplostim
arm group label: Romiplostim
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Emilie Le Rhun, MD
role: Principal Investigator
affiliation: CHRU Lille
facility: 
facility: 
facility: 
facility: 
country: France
citation: Armstrong TS, Cao Y, Scheurer ME, Vera-Bolanos E, Manning R, Okcu MF, Bondy M, Zhou R, Gilbert MR. Risk analysis of severe myelotoxicity with temozolomide: the effects of clinical and genetic factors. Neuro Oncol. 2009 Dec;11(6):825-32. doi: 10.1215/15228517-2008-120.
PMID: 19179423
citation: Gerber DE, Grossman SA, Zeltzman M, Parisi MA, Kleinberg L. The impact of thrombocytopenia from temozolomide and radiation in newly diagnosed adults with high-grade gliomas. Neuro Oncol. 2007 Jan;9(1):47-52. doi: 10.1215/15228517-2006-024. Epub 2006 Nov 15.
PMID: 17108062
citation: George JN, Raskob GE, Shah SR, Rizvi MA, Hamilton SA, Osborne S, Vondracek T. Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med. 1998 Dec 1;129(11):886-90. doi: 10.7326/0003-4819-129-11_part_1-199812010-00009.
PMID: 9867731
citation: Kuter DJ, Rummel M, Boccia R, Macik BG, Pabinger I, Selleslag D, Rodeghiero F, Chong BH, Wang X, Berger DP. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010 Nov 11;363(20):1889-99. doi: 10.1056/NEJMoa1002625.
PMID: 21067381
citation: Molineux G. The development of romiplostim for patients with immune thrombocytopenia. Ann N Y Acad Sci. 2011 Mar;1222:55-63. doi: 10.1111/j.1749-6632.2011.05975.x.
PMID: 21434943
citation: Sure D, Dunn I, Norden A, Anderson WS. Intracerebral hemorrhage secondary to thrombocytopenia in a patient treated with temozolomide. Clin Neurol Neurosurg. 2010 Oct;112(8):741-2. doi: 10.1016/j.clineuro.2010.04.005.
PMID: 20434832
citation: Mutter N, Stupp R. Temozolomide: a milestone in neuro-oncology and beyond? Expert Rev Anticancer Ther. 2006 Aug;6(8):1187-204. doi: 10.1586/14737140.6.8.1187.
PMID: 16925485
citation: Oh J, Kutas GJ, Davey P, Morrison M, Perry JR. Aplastic anemia with concurrent temozolomide treatment in a patient with glioblastoma multiforme. Curr Oncol. 2010 Aug;17(4):124-6. doi: 10.3747/co.v17i4.526.
PMID: 20697524
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Thrombocytopenia
sharing ipd: No