<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/NCT03763123</url>
  </required_header>
  <id_info>
    <org_study_id>SIM-63-OC-101</org_study_id>
    <nct_id>NCT03763123</nct_id>
  </id_info>
  <brief_title>A Phase 1b Study of Sevacizumab in Combination With Chemotherapy in Chinese Patients With Platinum-Resistant Recurrent Ovarian Cancer.</brief_title>
  <official_title>A Phase Ib, Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody(Sevacizumab) Injection Plus Chemotherapy in Chinese Patients With Platinum-Resistant Recurrent Ovarian Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu Simcere Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jiangsu Simcere Pharmaceutical Co., Ltd.</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>
      This is an open-label, multicenter, dose-escalation study designed to assess the safety,&#xD;
      tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab)&#xD;
      Injection in combination with Chemotherapy in Chinese patients with Platinum-Resistant&#xD;
      Recurrent Ovarian Cancer. This study includes two stages. Stage 1 is the dose-escalation&#xD;
      stage. Once the maximum tolerated dose (MTD of Sevacizumab has been established, additional&#xD;
      patients will be enrolled in the cohort-expansion stage (Stage 2).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, multicenter, dose-escalation study designed to assess the safety,&#xD;
      tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab)&#xD;
      Injection in combination with Chemotherapy in Chinese patients with Platinum-Resistant&#xD;
      Recurrent Ovarian Cancer. This study includes two stages. Stage 1 is the dose-escalation&#xD;
      stage. Once the maximum tolerated dose (MTD of Sevacizumab has been established, additional&#xD;
      patients will be enrolled in the cohort-expansion stage (Stage 2).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 24, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</primary_completion_date>
  <phase>Phase 1</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>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>3 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>The ratio of adverse of event</measure>
    <time_frame>3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration [Cmax]</measure>
    <time_frame>3 years</time_frame>
    <description>Maximum Plasma Concentration [Cmax]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve [AUC],</measure>
    <time_frame>3 years</time_frame>
    <description>Area Under the Curve [AUC]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>3 years</time_frame>
    <description>Tmax for Cmax of sevacizumab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">48</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>Sevacizumab +Chemotherapy Combined chemotherapy drug including</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Investigators selected single-agent chemotherapy on an individual patient basis from the following options, with appropriate premedication according to local standards: paclitaxel 80mg/m2 intravenously (IV)on days 1, 8, 15, and 22 every 4 weeks; or topotecan 4 mg/m2 IV on days 1, 8, and 15 every 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sevacizumab</intervention_name>
    <description>Drug: Sevacizumab escalating doses of Sevacizumab : 0.5mg/kg，1mg/kg，1.5mg/kg and 2mg/kg</description>
    <arm_group_label>Sevacizumab +Chemotherapy Combined chemotherapy drug including</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>paclitaxel 80mg/m2 as a &gt; 3-hour IV infusion on days 1, 8,15, and 22 every 4 weeks;</description>
    <arm_group_label>Sevacizumab +Chemotherapy Combined chemotherapy drug including</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topotecan</intervention_name>
    <description>topotecan 4 mg/m2 as a &gt;30 minute IV infusion on days 1, 8, and 15 every 4 weeks ;</description>
    <arm_group_label>Sevacizumab +Chemotherapy Combined chemotherapy drug including</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. age≥18 years&#xD;
&#xD;
          2. Histologically documented platinum resistant&#xD;
&#xD;
          3. EOC, FTC, or PPC of the following types: adenocarcinoma not otherwise specified (NOS),&#xD;
             clear cell adenocarcinoma, endometriod adenocarcinoma, malignant Brenner's tumor,&#xD;
             mixed epithelial carcinoma, mucinous adenocarcinoma, serous adenocarcinoma,&#xD;
             transitional cell carcinoma and undifferentiated carcinoma.&#xD;
&#xD;
          4. At least one measurable leision. (according to RECIST 1.1 )&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.&#xD;
&#xD;
          6. Adequate hematologic function: ANC ≥ 1.5 × 10^9 /L, HB ≥ 90 g /L (blood transfusion&#xD;
             allowed), PLT ≥ 100 ×10^9 /L; Adequate hepatic function: ALT ≤ 2.5 × ULN, AST ≤ 2.5 ×&#xD;
             ULN, TBIL ≤ 1.5 × ULN (patients with liver metastases ALT ≤ 5 × ULN, AST ≤ 5 × ULN);&#xD;
             Adequate renal function: creatinine ≤ 1 × ULN; Coagulation function: INR ≤ 1.5 × ULN,&#xD;
             APTT ≤ 1.5 × ULN&#xD;
&#xD;
          7. Progression within 6 months from completion of a minimum of 4 platinum therapy cycles.&#xD;
&#xD;
          8. Life expectancy ≥12 weeks.&#xD;
&#xD;
          9. At least 4 weeks from the last chemotherapy. If patients received anti-tumor&#xD;
             biological products, at least four t1/2 of washout period is needed&#xD;
&#xD;
         10. Toxicity from previous treatment has to restore to ≤ grade 1 (NCI CTC4.0)&#xD;
&#xD;
         11. Patients signed written inform consent.&#xD;
&#xD;
         12. Willingness and capability to communicate with investigators and to comply with&#xD;
             protocol requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous treatment with &gt; 2 anti-cancer regimens.&#xD;
&#xD;
          2. Patients whose disease was refractory to their previous platinum treatment.&#xD;
             (Refractory disease was defined as those patients who progressed during the preceding&#xD;
             platinum treatment.)&#xD;
&#xD;
          3. Ovarian tumors with low malignant potential (i.e. borderline tumors).&#xD;
&#xD;
          4. Patients with a prior invasive malignancy (except non-melanoma skin cancer) or whose&#xD;
             prior malignancy treatment contraindicated the current protocol therapy.&#xD;
&#xD;
          5. Any prior radiotherapy to the pelvis or abdomen.&#xD;
&#xD;
          6. Patients with serious non-healing wound, ulcer, or bone fracture.&#xD;
&#xD;
          7. patients with a history of bowel obstruction (including subocclusive disease) related&#xD;
             to underlying disease, a history of abdominal fistula, GI perforation, or&#xD;
             intra-abdominal abscess or evidence of rectosigmoid involvement by pelvic examination,&#xD;
             bowel involvement on computed tomography, or clinical symptoms of bowel obstruction.&#xD;
&#xD;
          8. Serious infection requiring intravenous antibiotic therapy&#xD;
&#xD;
          9. history or evidence of thrombotic or hemorrhagic disorder within 6 months before first&#xD;
             study treatment&#xD;
&#xD;
         10. untreated CNS disease unrelated to cancer or symptomatic CNS metastasis&#xD;
&#xD;
         11. Patients with clinically significant cardiovascular disease. This&#xD;
             included:Uncontrolled hypertension, defined as systolic &gt; 150 mmHg or diastolic &gt; 90&#xD;
             mmHg;Myocardial infarction or unstable angina &gt; 6 months prior to registration;New&#xD;
             York Heart Association (NYHA) Grade II or greater congestive heart failure;Serious&#xD;
             cardiac arrhythmia requiring medication. This did not include asymptomatic, atrial&#xD;
             fibrillation with controlled ventricular rate.&#xD;
&#xD;
         12. left ventricular ejection fraction below the institutional lower limit of normal&#xD;
&#xD;
         13. pre-existing neuropathy ≥ CTC Grade 2 for those in the paclitaxel group&#xD;
&#xD;
         14. Known allergies to any excipient in the study drug&#xD;
&#xD;
         15. Pregnant and lactating women&#xD;
&#xD;
         16. Patients with proteinuria (urine protein &gt;1+ at screening, or urine protein 1+, not&#xD;
             recover to normal value within 24h)&#xD;
&#xD;
         17. Previously received anti-VEGF protein drugs, such as Bevacizumab, Sevacizumab&#xD;
&#xD;
         18. Patients with or with anticipation of invasive procedures as defined below:Major&#xD;
             surgical procedure or significant traumatic injury within 28 days prior to the first&#xD;
             date of sevacizumab therapy;Major surgical procedure anticipated during the course of&#xD;
             the study. This included, but was not limited to abdominal surgery (laparotomy or&#xD;
             laparoscopy) prior to disease progression;Core biopsy, within 7 days prior to&#xD;
             randomization.&#xD;
&#xD;
         19. Participation in other clinical trials within 4 weeks before enrollment&#xD;
&#xD;
         20. The investigators consider the patients are not suitable for this trial.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Beijing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>zheng hong</last_name>
      <phone>010-88196102</phone>
      <email>zhhong306@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>zheng hong</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cancer Hospital Chinese Academy of Medical Sciences</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wu Lingying</last_name>
      <phone>010-87788787</phone>
      <email>wulingying@csco.org.cn</email>
    </contact>
    <investigator>
      <last_name>wu lingying</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The first affiliated hospital,sun yat-sen university</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yao Shuzhong</last_name>
      <phone>020-87755766</phone>
      <phone_ext>8185</phone_ext>
      <email>yszlfy@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Yao Shuzhong</last_name>
      <phone>02087755766</phone>
      <phone_ext>02087755766</phone_ext>
      <email>yszlfy@163.com</email>
    </contact_backup>
    <investigator>
      <last_name>Yao Shuzhong</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>the Affiliated Cancer Hospital of Harbin Medical University</name>
      <address>
        <city>Harbin</city>
        <state>Hei Longjiang</state>
        <country>China</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Hunan Cancer Hospital</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhang Keqiang</last_name>
      <phone>0731-89762695</phone>
      <phone_ext>073189762695</phone_ext>
      <email>1465217100@qq.com</email>
    </contact>
    <contact_backup>
      <last_name>Zhang Keqiang</last_name>
      <phone>073189762695</phone>
      <phone_ext>073189762695</phone_ext>
      <email>1465217100@qq.com</email>
    </contact_backup>
    <investigator>
      <last_name>Zhang Keqiang</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Wuhan Union Hospital</name>
      <address>
        <city>Wuhan</city>
        <state>Hunan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Li Guiling</last_name>
      <phone>027-83691785</phone>
      <email>lgl6714@163.com</email>
    </contact>
    <investigator>
      <last_name>Li Guiling</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>November 25, 2018</study_first_submitted>
  <study_first_submitted_qc>December 1, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <last_update_submitted>December 1, 2018</last_update_submitted>
  <last_update_submitted_qc>December 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Paclitaxel</mesh_term>
    <mesh_term>Topotecan</mesh_term>
  </intervention_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/NCT03763123
org study id: SIM-63-OC-101
nct id: NCT03763123
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is an open-label, multicenter, dose-escalation study designed to assess the safety,
      tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab)
      Injection in combination with Chemotherapy in Chinese patients with Platinum-Resistant
      Recurrent Ovarian Cancer. This study includes two stages. Stage 1 is the dose-escalation
      stage. Once the maximum tolerated dose (MTD of Sevacizumab has been established, additional
      patients will be enrolled in the cohort-expansion stage (Stage 2).
This is an open-label, multicenter, dose-escalation study designed to assess the safety,
      tolerability, and pharmacokinetics of Humanized Anti-VEGF Monoclonal Antibody (Sevacizumab)
      Injection in combination with Chemotherapy in Chinese patients with Platinum-Resistant
      Recurrent Ovarian Cancer. This study includes two stages. Stage 1 is the dose-escalation
      stage. Once the maximum tolerated dose (MTD of Sevacizumab has been established, additional
      patients will be enrolled in the cohort-expansion stage (Stage 2).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: 3 years
measure: The ratio of adverse of event
time frame: 3 years
measure: Maximum Plasma Concentration [Cmax]
time frame: 3 years
description: Maximum Plasma Concentration [Cmax]
measure: Area Under the Curve [AUC],
time frame: 3 years
description: Area Under the Curve [AUC]
measure: Tmax
time frame: 3 years
description: Tmax for Cmax of sevacizumab
measure: Objective Response Rate (ORR)
time frame: 3 years
measure: Disease Control Rate (DCR)
time frame: 3 years
measure: Overall Survival (OS)
time frame: 3 years
measure: Progression Free Survival (PFS)
time frame: 3 years
arm group label: Sevacizumab +Chemotherapy Combined chemotherapy drug including
arm group type: Experimental
description: Investigators selected single-agent chemotherapy on an individual patient basis from the following options, with appropriate premedication according to local standards: paclitaxel 80mg/m2 intravenously (IV)on days 1, 8, 15, and 22 every 4 weeks; or topotecan 4 mg/m2 IV on days 1, 8, and 15 every 4 weeks.
intervention type: Drug
intervention name: Sevacizumab
description: Drug: Sevacizumab escalating doses of Sevacizumab : 0.5mg/kg，1mg/kg，1.5mg/kg and 2mg/kg
arm group label: Sevacizumab +Chemotherapy Combined chemotherapy drug including
intervention type: Drug
intervention name: Paclitaxel
description: paclitaxel 80mg/m2 as a > 3-hour IV infusion on days 1, 8,15, and 22 every 4 weeks;
arm group label: Sevacizumab +Chemotherapy Combined chemotherapy drug including
intervention type: Drug
intervention name: Topotecan
description: topotecan 4 mg/m2 as a >30 minute IV infusion on days 1, 8, and 15 every 4 weeks ;
arm group label: Sevacizumab +Chemotherapy Combined chemotherapy drug including
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Suspended
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Paclitaxel
mesh term: Topotecan
sharing ipd: No