<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/NCT02263105</url>
  </required_header>
  <id_info>
    <org_study_id>CAT001</org_study_id>
    <secondary_id>Huashan H</secondary_id>
    <nct_id>NCT02263105</nct_id>
  </id_info>
  <brief_title>Efficacy and Tolerability of Cisplatin Plus Alternating Weekly Temozolomide in Recurrent High-grade Gliomas</brief_title>
  <official_title>Efficacy and Tolerability of Cisplatin Plus Alternating Weekly Temozolomide in Recurrent High-grade Gliomas: A Single-arm Prospective Phase II Clinical Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Huashan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Huashan Hospital</source>
  <brief_summary>
    <textblock>
      Currently, the prognosis of recurrent high-grade gliomas is still dismal with no standard&#xD;
      treatment protocol established. Cisplatin (CDDP), recommended by National Comprehensive&#xD;
      Cancer Network (NCCN) as a chemotherapeutic agent in salvage treatment for recurrent&#xD;
      high-grade gliomas, was shown to reduce O6-alkylguanine DNA-alkyl transferase (AGAT) activity&#xD;
      and potentially capable of enhancing the antitumor effects of temozolomide (TMZ). Compared to&#xD;
      the standard 5-day TMZ regimen, alternating weekly regimen that deliver more prolonged&#xD;
      exposure of TMZ may lead to higher cumulative doses, and may deplete more O6-methylguanine&#xD;
      DNA methyltransferase (MGMT), thus reducing the resistance of tumor cells to TMZ.&#xD;
&#xD;
      The investigators therefore initiate a single-arm Phase II study to evaluate the efficacy and&#xD;
      tolerability of CDDP plus alternating weekly TMZ regimen in patients with recurrent&#xD;
      high-grade gliomas.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2014</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">May 2018</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>progression free survival (PFS)</measure>
    <time_frame>at 6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall survival(OS)</measure>
    <time_frame>at 1 year and 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">67</enrollment>
  <condition>High-grade Gliomas</condition>
  <arm_group>
    <arm_group_label>CDDP plus Temozolomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients were treated with CDDP and TMZ. CDDP was administered iv from Day 1 to 3 with everyday dose of 30mg. TMZ was orally administered from Day 1 to 7 and Day 15 to 21, with everyday dose of 125mg/m2 (Level 2). The period of one chemotherapy cycle is 28 days. TMZ dose levels were listed in Table 1.&#xD;
Table 1 TMZ dose levels Dose levels Daily TMZ dose( mg/m2/d ) TMZ dose per cycle(mg/m2)&#xD;
150 2100&#xD;
125 1750&#xD;
100 1400&#xD;
75 1050</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CDDP</intervention_name>
    <arm_group_label>CDDP plus Temozolomide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Temozolomide</intervention_name>
    <description>If hematologic and nonhematologic toxicity assessed according to the Common Terminology Criteria for Adverse Events (CTCAE; version 4.0) from the previous cycle had been grade 0 or 1, then TMZ dose escalation to was allowed to the maximum of 150 mg/m2. If grade 4 hematologic toxicity or grade 3 nonhematologic toxicity had occurred, then TMZ dose was reduced in 25 mg/m2 steps. If grade 4 nonhematologic toxicity occurred, patient treatment was halted. If grade 4 hematologic toxicity or grade 3 nonhematologic toxicity continued when TMZ dose was in the minimum of 75 mg/m2, patient treatment was halted.</description>
    <arm_group_label>CDDP plus Temozolomide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histological diagnosis of primary tumor as high-grade gliomas (WHO III or IV)&#xD;
&#xD;
          -  All patients should complete radiation therapy for primary gliomas.&#xD;
&#xD;
          -  MRI showed unequivocal evidence of tumor recurrence or progression.&#xD;
&#xD;
          -  The time to be enrolled should be more than 90 days after the radiation therapy.&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group(ECOG) score: 0-2&#xD;
&#xD;
          -  The patients with recurrent gliomas were treated without dose-dense TMZ therapy before&#xD;
             enrollment.&#xD;
&#xD;
          -  Surgical interventions for recurrent gliomas are permitted and patients with no&#xD;
             residual tumor are permitted&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Abnormal function of liver or renal (value more than 1.5 fold normal upper limit)&#xD;
&#xD;
          -  Blood routing: Hb &lt; 90g/L, absolute neutrophil count≤1.5*10^9/L, platelet &lt; 100*10^9/L&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Allergic to administered drugs&#xD;
&#xD;
          -  Radiation therapy in the previous 90 days before enrollment&#xD;
&#xD;
          -  The patients with recurrent gliomas were treated with dose-dense TMZ therapy before&#xD;
             enrollment.&#xD;
&#xD;
          -  Acute infection in need of antibiotics intravenously&#xD;
&#xD;
          -  Participation in other clinical trials in the 90 days before enrollment&#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>Zhiyong Qin, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Huashan Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ying Mao, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Huashan Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yu Yao, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Huashan Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>ZhenYu Zhang</last_name>
    <role>Principal Investigator</role>
    <affiliation>Huashan Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Huashan Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200040</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 28, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>July 14, 2018</last_update_submitted>
  <last_update_submitted_qc>July 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Huashan Hospital</investigator_affiliation>
    <investigator_full_name>Zhang Zhenyu</investigator_full_name>
    <investigator_title>M.D.</investigator_title>
  </responsible_party>
  <keyword>recurrent high-grade gliomas</keyword>
  <keyword>cisplatin (CDDP)</keyword>
  <keyword>temozolomide (TMZ)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</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/NCT02263105
org study id: CAT001
secondary id: Huashan H
nct id: NCT02263105
lead sponsor: 
Currently, the prognosis of recurrent high-grade gliomas is still dismal with no standard
      treatment protocol established. Cisplatin (CDDP), recommended by National Comprehensive
      Cancer Network (NCCN) as a chemotherapeutic agent in salvage treatment for recurrent
      high-grade gliomas, was shown to reduce O6-alkylguanine DNA-alkyl transferase (AGAT) activity
      and potentially capable of enhancing the antitumor effects of temozolomide (TMZ). Compared to
      the standard 5-day TMZ regimen, alternating weekly regimen that deliver more prolonged
      exposure of TMZ may lead to higher cumulative doses, and may deplete more O6-methylguanine
      DNA methyltransferase (MGMT), thus reducing the resistance of tumor cells to TMZ.

      The investigators therefore initiate a single-arm Phase II study to evaluate the efficacy and
      tolerability of CDDP plus alternating weekly TMZ regimen in patients with recurrent
      high-grade gliomas.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: progression free survival (PFS)
time frame: at 6 months
measure: overall survival(OS)
time frame: at 1 year and 2 years
arm group label: CDDP plus Temozolomide
arm group type: Experimental
description: Patients were treated with CDDP and TMZ. CDDP was administered iv from Day 1 to 3 with everyday dose of 30mg. TMZ was orally administered from Day 1 to 7 and Day 15 to 21, with everyday dose of 125mg/m2 (Level 2). The period of one chemotherapy cycle is 28 days. TMZ dose levels were listed in Table 1.
Table 1 TMZ dose levels Dose levels Daily TMZ dose( mg/m2/d ) TMZ dose per cycle(mg/m2)
150 2100
125 1750
100 1400
75 1050
intervention type: Drug
intervention name: CDDP
arm group label: CDDP plus Temozolomide
intervention type: Drug
intervention name: Temozolomide
description: If hematologic and nonhematologic toxicity assessed according to the Common Terminology Criteria for Adverse Events (CTCAE; version 4.0) from the previous cycle had been grade 0 or 1, then TMZ dose escalation to was allowed to the maximum of 150 mg/m2. If grade 4 hematologic toxicity or grade 3 nonhematologic toxicity had occurred, then TMZ dose was reduced in 25 mg/m2 steps. If grade 4 nonhematologic toxicity occurred, patient treatment was halted. If grade 4 hematologic toxicity or grade 3 nonhematologic toxicity continued when TMZ dose was in the minimum of 75 mg/m2, patient treatment was halted.
arm group label: CDDP plus Temozolomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Zhiyong Qin, MD
role: Study Chair
affiliation: Huashan Hospital
last name: Ying Mao, MD
role: Principal Investigator
affiliation: Huashan Hospital
last name: Yu Yao, MD
role: Principal Investigator
affiliation: Huashan Hospital
last name: ZhenYu Zhang
role: Principal Investigator
affiliation: Huashan Hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Huashan Hospital
investigator full name: Zhang Zhenyu
investigator title: M.D.
mesh term: Glioma
mesh term: Temozolomide