<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/NCT03298074</url>
  </required_header>
  <id_info>
    <org_study_id>HRGX-001</org_study_id>
    <nct_id>NCT03298074</nct_id>
  </id_info>
  <brief_title>Apatinib Plus Etoposide Versus Etoposide Alone for Platinum-resistant Recurrent Ovarian Cancer</brief_title>
  <official_title>Apatinib Plus Etoposide Versus Etoposide Alone for Platinum-resistant Recurrent Ovarian Cancer: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yang Zhijun</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Guangxi Medical University</source>
  <oversight_info>
    <has_dmc>No</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>
      It is a prospective multi-center trial, platinum-resistant ovarian cancer patients will be&#xD;
      randomized in two groups, one group will be treated with Apatinib plus Etoposide, the other&#xD;
      will be treated with Etoposide alone. It is aimed to see the efficacy and safety of Apatinib&#xD;
      plus Etoposide for the platinum-resistant ovarian cancer patients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is a randomized controlled trial, the aim is to see the efficacy and safety of Apatinib&#xD;
      plus Etoposide treating platinum-resistant ovarian cancer. The main primary end point is DCR&#xD;
      (disease control rate), the secondary endpoint is Duration of response（DOR），overall survival&#xD;
      (OS), time to progression (TTP)，quality of life (QoL, according to EORTC QLQ-C30).The key&#xD;
      safety indicators include the patients' vital signs, laboratory indicators, adverse&#xD;
      events(AE),serious adverse events.&#xD;
&#xD;
      The data collection duration is from the day ICF assigned to the day(30 days after the end of&#xD;
      the last medication).From the day ICF signed to the end of the study, all adverse events were&#xD;
      recorded in the CRF. The severity of the adverse events will be evaluated according to the&#xD;
      NCI CTCAE 4.0 standard.Each patient will receive a planned visit and specific data at&#xD;
      different points will be recorded in the visit.&#xD;
&#xD;
      The patients will be followed up after quitting the trial because of disease progression or&#xD;
      intolerance. The following parameters were recorded during follow-up: disease&#xD;
      recurrence,metastasis,death time,SAE occurred during the study; survival (available with&#xD;
      telephone follow-up, record required).&#xD;
&#xD;
      Adverse events that have not been recovered when the drug is discontinued should be tracked&#xD;
      and finalized. All patients should undergo a 30-day follow-up after the last medication to&#xD;
      find any new adverse events.&#xD;
&#xD;
      All cases should be recorded carefully and completely, the investigator should be responsible&#xD;
      for the authenticity of the center's data.&#xD;
&#xD;
      During the clinical trial, the inspector should send the CRF to the data management unit (in&#xD;
      batches), the data administrator will carry out the independent double entry, and carry out&#xD;
      the double verification.&#xD;
&#xD;
      The trial as an exploratory test, using a small sample comparison, the test plans to enroll a&#xD;
      total of 60 cases.&#xD;
&#xD;
      The statistical analysis plan includes case analysis,demographic data and baseline&#xD;
      analysis,efficacy analysis and safety analysis.All statistical tests will be performed on&#xD;
      both sides, the difference between the tests was considered statistically significant with a&#xD;
      P value less than or equal to 0.05,&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">October 2017</start_date>
  <completion_date type="Anticipated">April 2019</completion_date>
  <primary_completion_date type="Anticipated">October 2018</primary_completion_date>
  <phase>Phase 2</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, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Disease Control Rate</measure>
    <time_frame>through study completion, an average of 1.5 years</time_frame>
    <description>the proportion of patients who had a best response rating of complete response, partial response, or stable disease</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>through study completion, an average of 1.5 years</time_frame>
    <description>the time course from the first time tumor assessed as CR or PR to the first time tumor assessed as progressive disease or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>through study completion, an average of 3 years</time_frame>
    <description>From the beginning of randomization to the cause of death for any reason</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression</measure>
    <time_frame>through study completion, an average of 1.5 years</time_frame>
    <description>From randomization to the onset of disease progression or death</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>Apatinib plus Etoposide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Apatinib,500mg,PO.QD, continuous administration Etoposide,100mg, PO.QD，D1-D10, Q3W</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Etoposide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Etoposide,100mg, PO.QD，D1-D10, Q3W</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>Apatinib, 500mg,po qd for continuous administration</description>
    <arm_group_label>Apatinib plus Etoposide</arm_group_label>
    <other_name>Aitan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>Etoposide,100mg, PO.QD，D1-D10, Q3W</description>
    <arm_group_label>Apatinib plus Etoposide</arm_group_label>
    <arm_group_label>Etoposide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ECOG PS：0-2 points&#xD;
&#xD;
          -  Platinum-resistant recurrent ovarian cancer patients with measurable recurrent focus&#xD;
&#xD;
          -  The damage caused by other treatment has been restored (NCI-CTCAE 4.0 Graded ≤ 1&#xD;
             level), Other cytotoxic drugs treatment, radiotherapy or surgery≥ 4 week; EGFR TKI&#xD;
             treatment ≥ 2 week&#xD;
&#xD;
          -  Baseline routine blood test and biochemical indicators meet the following criteria:&#xD;
&#xD;
               -  Hemoglobin ≥ 90g / L&#xD;
&#xD;
               -  Neutrophil absolute count (ANC) ≥ 1.5 × 109 / L&#xD;
&#xD;
               -  Platelets ≥80 × 109 / L&#xD;
&#xD;
               -  ALT, AST ≤ 2.5 × ULN or 5 × ULN (with liver metastases)&#xD;
&#xD;
               -  Total Serum bilirubin ≤ 1.5 × ULN&#xD;
&#xD;
               -  Serum creatinine≤1.5×ULN or endogenous creatinine clearance ≥ 45ml/min (according&#xD;
                  to Cockcroft-Gault formula);&#xD;
&#xD;
          -  No blood and blood products transfusion in 14 Days&#xD;
&#xD;
          -  Expected survival time≥3 month;&#xD;
&#xD;
          -  Subjects volunteer to join the study, sign informed consent, cooperate with follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  &quot;biochemical recurrence &quot; ovarian cancer patients&#xD;
&#xD;
          -  Patients allergy to apatinib, etoposide and / or its excipients&#xD;
&#xD;
          -  Patients with high blood pressure and who can not be reduced to normal range by&#xD;
             antihypertensive therapy (systolic blood pressure&gt; 140 mmHg, diastolic blood pressure&gt;&#xD;
             90 mmHg), with grade I coronary heart disease, grade I arrhythmia (including QTc&#xD;
             prolongation &gt; 470 ms)&#xD;
&#xD;
          -  According to NYHA standard, grade Ⅲ-Ⅳ heart failure, or cardiac color Doppler&#xD;
             ultrasound examination shows left ventricular ejection fraction (LVEF) &lt;50%&#xD;
&#xD;
          -  Urine protein positive patients&#xD;
&#xD;
          -  With a variety of factors that affect oral medication (such as can not swallow,&#xD;
             nausea, vomiting, chronic diarrhea and intestinal obstruction, etc.)&#xD;
&#xD;
          -  Patients with definite gastrointestinal bleeding tendencies, including the following:&#xD;
             localized ulcer lesions, and fecal occult blood (++); 2 months with black stool,&#xD;
             hematemesis history&#xD;
&#xD;
          -  Patients with coagulation dysfunction (INR&gt; 1.5, APTT&gt; 1.5 ULN), bleeding tendency&#xD;
&#xD;
          -  Existing hereditary or acquired bleeding and thrombotic tendencies (such as&#xD;
             hemophilia, coagulation disorders, thrombocytopenia, hypersplenism, etc.)&#xD;
&#xD;
          -  Long untreated wound or fracture;major surgery or severe traumatic injury in 4 weeks,&#xD;
             fracture or ulcer&#xD;
&#xD;
          -  Accompanied by abdominal fistula, gastrointestinal perforation or abdominal abscess;&#xD;
             active hepatitis B virus or hepatitis C patients&#xD;
&#xD;
          -  Active brain metastases, cancer meningitis, spinal cord compression patients, Imaging&#xD;
             CT or MRI examination found the brain or pia mater disease,( brain metastases patients&#xD;
             who has complete treatment 21 days before and has stable symptoms can be enrolled ,&#xD;
             but the need for transcranial MRI, CT or intravenous angiography evaluation confirmed&#xD;
             as no cerebral hemorrhage symptoms)&#xD;
&#xD;
          -  Imaging (CT or MRI) shows tumor lesions from large vessels ≤ 5 mm, or lesions invade&#xD;
             the Local large blood vessels&#xD;
&#xD;
          -  Lactating women&#xD;
&#xD;
          -  Patients with other malignancies in 5 years (except for cured skin basal cell&#xD;
             carcinoma and in situ ovarian cancer)&#xD;
&#xD;
          -  Patients with a history of psychiatric abuse and who can not quit or have mental&#xD;
             disorders&#xD;
&#xD;
          -  Patients who participated in other drug clinical trials within 4 weeks&#xD;
&#xD;
          -  Patients who received VEGFR inhibitors such as sorafenib and sunitinib treatment&#xD;
&#xD;
          -  Patients who received Etoposide treatment&#xD;
&#xD;
          -  According to the researcher's judgment, there are serious illnesses that endanger the&#xD;
             patient's safety or affect the completion of the study&#xD;
&#xD;
          -  Patients that are not suitable for this trial in the investigator's opinions.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>female patient with recurrent ovarian cancer</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhijun Yang</last_name>
    <role>Principal Investigator</role>
    <affiliation>Affiliated Cancer Hospital &amp; Institute of Guangzhou Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zhijun Yang</last_name>
    <phone>8618994127461</phone>
    <email>18994127461@163.com</email>
  </overall_contact>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>September 28, 2017</last_update_submitted>
  <last_update_submitted_qc>September 28, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Guangxi Medical University</investigator_affiliation>
    <investigator_full_name>Yang Zhijun</investigator_full_name>
    <investigator_title>Associate chief physician</investigator_title>
  </responsible_party>
  <keyword>platinum-resistant</keyword>
  <keyword>recurrent</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Apatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03298074
org study id: HRGX-001
nct id: NCT03298074
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
It is a prospective multi-center trial, platinum-resistant ovarian cancer patients will be
      randomized in two groups, one group will be treated with Apatinib plus Etoposide, the other
      will be treated with Etoposide alone. It is aimed to see the efficacy and safety of Apatinib
      plus Etoposide for the platinum-resistant ovarian cancer patients
It is a randomized controlled trial, the aim is to see the efficacy and safety of Apatinib
      plus Etoposide treating platinum-resistant ovarian cancer. The main primary end point is DCR
      (disease control rate), the secondary endpoint is Duration of response（DOR），overall survival
      (OS), time to progression (TTP)，quality of life (QoL, according to EORTC QLQ-C30).The key
      safety indicators include the patients' vital signs, laboratory indicators, adverse
      events(AE),serious adverse events.

      The data collection duration is from the day ICF assigned to the day(30 days after the end of
      the last medication).From the day ICF signed to the end of the study, all adverse events were
      recorded in the CRF. The severity of the adverse events will be evaluated according to the
      NCI CTCAE 4.0 standard.Each patient will receive a planned visit and specific data at
      different points will be recorded in the visit.

      The patients will be followed up after quitting the trial because of disease progression or
      intolerance. The following parameters were recorded during follow-up: disease
      recurrence,metastasis,death time,SAE occurred during the study; survival (available with
      telephone follow-up, record required).

      Adverse events that have not been recovered when the drug is discontinued should be tracked
      and finalized. All patients should undergo a 30-day follow-up after the last medication to
      find any new adverse events.

      All cases should be recorded carefully and completely, the investigator should be responsible
      for the authenticity of the center's data.

      During the clinical trial, the inspector should send the CRF to the data management unit (in
      batches), the data administrator will carry out the independent double entry, and carry out
      the double verification.

      The trial as an exploratory test, using a small sample comparison, the test plans to enroll a
      total of 60 cases.

      The statistical analysis plan includes case analysis,demographic data and baseline
      analysis,efficacy analysis and safety analysis.All statistical tests will be performed on
      both sides, the difference between the tests was considered statistically significant with a
      P value less than or equal to 0.05,
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Disease Control Rate
time frame: through study completion, an average of 1.5 years
description: the proportion of patients who had a best response rating of complete response, partial response, or stable disease
measure: Duration of Response
time frame: through study completion, an average of 1.5 years
description: the time course from the first time tumor assessed as CR or PR to the first time tumor assessed as progressive disease or death
measure: Overall Survival
time frame: through study completion, an average of 3 years
description: From the beginning of randomization to the cause of death for any reason
measure: Time to Progression
time frame: through study completion, an average of 1.5 years
description: From randomization to the onset of disease progression or death
arm group label: Apatinib plus Etoposide
arm group type: Experimental
description: Apatinib,500mg,PO.QD, continuous administration Etoposide,100mg, PO.QD，D1-D10, Q3W
arm group label: Etoposide
arm group type: Active Comparator
description: Etoposide,100mg, PO.QD，D1-D10, Q3W
intervention type: Drug
intervention name: Apatinib
description: Apatinib, 500mg,po qd for continuous administration
arm group label: Apatinib plus Etoposide
other name: Aitan
intervention type: Drug
intervention name: Etoposide
description: Etoposide,100mg, PO.QD，D1-D10, Q3W
arm group label: Apatinib plus Etoposide
arm group label: Etoposide
criteria: 
gender: Female
gender based: Yes
gender description: female patient with recurrent ovarian cancer
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Zhijun Yang
role: Principal Investigator
affiliation: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
last name: Zhijun Yang
phone: 8618994127461
email: 18994127461@163.com
responsible party type: Sponsor-Investigator
investigator affiliation: Guangxi Medical University
investigator full name: Yang Zhijun
investigator title: Associate chief physician
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Etoposide
mesh term: Apatinib
sharing ipd: Undecided