<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/NCT04473339</url>
  </required_header>
  <id_info>
    <org_study_id>2020107</org_study_id>
    <nct_id>NCT04473339</nct_id>
  </id_info>
  <brief_title>A Randomized Prospective Trail of HIPEC in Recurrent Ovarian Cancer Patients With HRR Mutation</brief_title>
  <official_title>A Randomized Prospective Trail of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Recurrent Ovarian Cancer Patients With Mutations in Homologous Recombination Repair (HRR) Genes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CAI Hongbing</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhongnan Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A phase III prospective study with the primary objective to investigate the benefit of&#xD;
      Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in ovarian cancer patients with mutations&#xD;
      in homologous recombination repair (HRR) genes. The target population for this study is&#xD;
      patients with recurrent ovarian, peritoneal or fallopian tube cancers undergoing&#xD;
      Cytoreductive Surgery (CRS). Patients will be divided into two groups according to HRR genes&#xD;
      mutation, each group will be further divided into two sub-groups with different intervention.&#xD;
      Patients in Group A are HRR mutated type, sub-group 1 will undergo CRS plus HIPEC and then go&#xD;
      on to receive standard platinum-based combination doublet intravenous chemotherapy, sub-group&#xD;
      2 will undergo CRS and then go on to intravenous chemotherapy. Patients in Group B are HRR&#xD;
      wild type, sub-group 3 will undergo CRS plus HIPEC and then go on to receive standard&#xD;
      platinum-based combination doublet intravenous chemotherapy, sub-group 4 will undergo CRS and&#xD;
      then go on to intravenous chemotherapy. All patients will receive maintenance therapy with&#xD;
      Niraparib after primary treatment. Prognostic information will be collected for investigation&#xD;
      of survival benefits of patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">August 30, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>up to 36 months since diagnosis</time_frame>
    <description>The progression-free survival interval was the time between diagnosis and evidence of recurrent or progressive disease.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>up to 36 months since histological diagnosis</time_frame>
    <description>The overall survival interval was the time between diagnosis and death or last follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DP9</measure>
    <time_frame>the 1 day of histological diagnosis and 9 months after</time_frame>
    <description>The 9 months progression-free survival rate was the rate of no evidence of recurrent or progressive disease at the time of 9 months since histological diagnosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DP12</measure>
    <time_frame>the 1 day of histological diagnosis and 12 months after</time_frame>
    <description>The 9 months progression-free survival rate was the rate of no evidence of recurrent or progressive disease at the time of 12 months since histological diagnosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious adverse events, SAEs</measure>
    <time_frame>surgery and with in 30 days</time_frame>
    <description>Serious adverse events occur within 30 days after surgery, measured with CTCAE 4.0</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">280</enrollment>
  <condition>Ovarian Cancer</condition>
  <condition>Epithelial Ovarian Cancer</condition>
  <condition>Ovarian Cancer, Epithelial</condition>
  <condition>Hyperthermic Intraperitoneal Chemotherapy(HIPEC)</condition>
  <condition>Homologous Recombination Repair Gene Mutation</condition>
  <arm_group>
    <arm_group_label>HRR mt 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients are HRR mutated type, will undergo CRS plus HIPEC and then go on to receive standard platinum-based combination doublet intravenous chemotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HRR mt 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients are HRR mutated type, will undergo CRS and then go on to receive standard platinum-based combination doublet intravenous chemotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HRR wt 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients are HRR wild type, will undergo CRS plus HIPEC and then go on to receive standard platinum-based combination doublet intravenous chemotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HRR wt 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients are HRR wild type, will undergo CRS and then go on to receive standard platinum-based combination doublet intravenous chemotherapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>CRS+HIPEC</intervention_name>
    <description>Patients will undergo only CRS, HIPEC and IVCT.Patients will receive standard platinum-based combination doublet chemotherapy for 6-8 cycles after CRS and then followed by maintenance therapy.&#xD;
A single drug lobaplatin(30mg/m2)will be administered in normal saline via HIPEC and it will be continued for 60 minutes in the hyperthermic phase (41°C-43°C). HIPEC will be performed at the 1st, 3rd and 5th day after CRS. The intravenous chemotherapy(IVCT) will start from 7th-14th day after CRS.</description>
    <arm_group_label>HRR mt 1</arm_group_label>
    <arm_group_label>HRR wt 3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>CRS alone</intervention_name>
    <description>Patients will undergo only CRS and IVCT.Patients will receive standard platinum-based combination doublet chemotherapy for 6-8 cycles after CRS and then followed by maintenance therapy.</description>
    <arm_group_label>HRR mt 2</arm_group_label>
    <arm_group_label>HRR wt 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age 18-75&#xD;
&#xD;
          -  Karnofsky performance status &gt;50 or World Health Organization performance score &lt; 2&#xD;
&#xD;
          -  primary or recurrence ovarian, peritoneal or fallopian tube epithelial cancer; first&#xD;
             intra-abdominal recurrence without distant metastasis (including: unique resectable&#xD;
             pleural metastasis which are platinum-sensitive; resectable single lymphatic&#xD;
             metastasis retroperitoneal or inguinal)&#xD;
&#xD;
          -  preoperative platinum-based chemotherapy (carboplatin and paclitaxel, carboplatin and&#xD;
             liposomal doxorubicin, gemcitabine, trabectedin or topotecan)&#xD;
&#xD;
          -  lesion can be removed completely or residual disease &lt; 0.5 cm&#xD;
&#xD;
          -  last chemotherapy finished no more than 12 weeks after surgery&#xD;
&#xD;
          -  no hepatic function damage&#xD;
&#xD;
          -  white blood cell count ≥3.5*10^9/L; platelet count ≥80*10^9/L; Hemoglobin ≥90g/L&#xD;
&#xD;
          -  no contraindication of surgery and anesthesia&#xD;
&#xD;
          -  life expectancy ≥ 3 months&#xD;
&#xD;
          -  informed consent form signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age &lt; 18 or &gt;75&#xD;
&#xD;
          -  no history of other cancer&#xD;
&#xD;
          -  platinum allergy&#xD;
&#xD;
          -  distant metastasis&#xD;
&#xD;
          -  used anti-angiogenic drug within 8 weeks&#xD;
&#xD;
          -  possibility of more than two resection of alimentary canal&#xD;
&#xD;
          -  recurrence &lt; 6 months after primary treatment&#xD;
&#xD;
          -  histologic type: non epithelial origin&#xD;
&#xD;
          -  infection out of control&#xD;
&#xD;
          -  follow-up unable to carry on (geographic or psychic)&#xD;
&#xD;
          -  cardiac insufficiency or respiratory insufficiency&#xD;
&#xD;
          -  has received HIPEC already&#xD;
&#xD;
          -  being in other clinical study&#xD;
&#xD;
          -  pregnancy or lactation period&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Hongbing Cai, Doctor</last_name>
    <phone>+86-27-67812648</phone>
    <email>chb2105@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zhen Li, Doctor</last_name>
    <phone>+86-27-67812648</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Zhongnan Hospital of Wuhan University</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430070</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yuanzhen Zhang, Doctor</last_name>
      <phone>+86-27-67812787</phone>
      <email>znyyll@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 12, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>September 4, 2020</last_update_submitted>
  <last_update_submitted_qc>September 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Zhongnan Hospital</investigator_affiliation>
    <investigator_full_name>CAI Hongbing</investigator_full_name>
    <investigator_title>Dr. Prof.</investigator_title>
  </responsible_party>
  <keyword>Homologous Recombination Repair Gene Mutation</keyword>
  <keyword>hyperthermic intraperitoneal chemotherapy</keyword>
  <keyword>Epithelial Ovarian Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Hyperthermia</mesh_term>
    <mesh_term>Fever</mesh_term>
  </condition_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/NCT04473339
org study id: 2020107
nct id: NCT04473339
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
A phase III prospective study with the primary objective to investigate the benefit of
      Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in ovarian cancer patients with mutations
      in homologous recombination repair (HRR) genes. The target population for this study is
      patients with recurrent ovarian, peritoneal or fallopian tube cancers undergoing
      Cytoreductive Surgery (CRS). Patients will be divided into two groups according to HRR genes
      mutation, each group will be further divided into two sub-groups with different intervention.
      Patients in Group A are HRR mutated type, sub-group 1 will undergo CRS plus HIPEC and then go
      on to receive standard platinum-based combination doublet intravenous chemotherapy, sub-group
      2 will undergo CRS and then go on to intravenous chemotherapy. Patients in Group B are HRR
      wild type, sub-group 3 will undergo CRS plus HIPEC and then go on to receive standard
      platinum-based combination doublet intravenous chemotherapy, sub-group 4 will undergo CRS and
      then go on to intravenous chemotherapy. All patients will receive maintenance therapy with
      Niraparib after primary treatment. Prognostic information will be collected for investigation
      of survival benefits of patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Progression-free Survival
time frame: up to 36 months since diagnosis
description: The progression-free survival interval was the time between diagnosis and evidence of recurrent or progressive disease.
measure: Overall Survival
time frame: up to 36 months since histological diagnosis
description: The overall survival interval was the time between diagnosis and death or last follow-up.
measure: DP9
time frame: the 1 day of histological diagnosis and 9 months after
description: The 9 months progression-free survival rate was the rate of no evidence of recurrent or progressive disease at the time of 9 months since histological diagnosis.
measure: DP12
time frame: the 1 day of histological diagnosis and 12 months after
description: The 9 months progression-free survival rate was the rate of no evidence of recurrent or progressive disease at the time of 12 months since histological diagnosis.
measure: Serious adverse events, SAEs
time frame: surgery and with in 30 days
description: Serious adverse events occur within 30 days after surgery, measured with CTCAE 4.0
arm group label: HRR mt 1
arm group type: Experimental
description: Patients are HRR mutated type, will undergo CRS plus HIPEC and then go on to receive standard platinum-based combination doublet intravenous chemotherapy.
arm group label: HRR mt 2
arm group type: Experimental
description: Patients are HRR mutated type, will undergo CRS and then go on to receive standard platinum-based combination doublet intravenous chemotherapy.
arm group label: HRR wt 3
arm group type: Experimental
description: Patients are HRR wild type, will undergo CRS plus HIPEC and then go on to receive standard platinum-based combination doublet intravenous chemotherapy.
arm group label: HRR wt 4
arm group type: Experimental
description: Patients are HRR wild type, will undergo CRS and then go on to receive standard platinum-based combination doublet intravenous chemotherapy.
intervention type: Procedure
intervention name: CRS+HIPEC
description: Patients will undergo only CRS, HIPEC and IVCT.Patients will receive standard platinum-based combination doublet chemotherapy for 6-8 cycles after CRS and then followed by maintenance therapy.
A single drug lobaplatin(30mg/m2)will be administered in normal saline via HIPEC and it will be continued for 60 minutes in the hyperthermic phase (41°C-43°C). HIPEC will be performed at the 1st, 3rd and 5th day after CRS. The intravenous chemotherapy(IVCT) will start from 7th-14th day after CRS.
arm group label: HRR mt 1
arm group label: HRR wt 3
intervention type: Procedure
intervention name: CRS alone
description: Patients will undergo only CRS and IVCT.Patients will receive standard platinum-based combination doublet chemotherapy for 6-8 cycles after CRS and then followed by maintenance therapy.
arm group label: HRR mt 2
arm group label: HRR wt 4
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Hongbing Cai, Doctor
phone: +86-27-67812648
email: chb2105@163.com
last name: Zhen Li, Doctor
phone: +86-27-67812648
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Zhongnan Hospital
investigator full name: CAI Hongbing
investigator title: Dr. Prof.
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Hyperthermia
mesh term: Fever