<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/NCT03244774</url>
  </required_header>
  <id_info>
    <org_study_id>FNF 007</org_study_id>
    <nct_id>NCT03244774</nct_id>
  </id_info>
  <brief_title>Phase I Study of the Combination of Apatinib and POF</brief_title>
  <official_title>Phase I Study of the Combination of Apatinib and POF (Paclitaxel Plus Oxaliplatin Plus 5-fluorouracil Plus Leucovorin)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fujian Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fujian Cancer Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In previous studies, we found that POF (A combination of oxaliplatin, fluorouracil and&#xD;
      Paclitaxel) regimen appears to be of good efficacy and is well tolerated in patients with&#xD;
      advanced gastric cancer. Apatinib is an orally antiangiogenic agent. It was approved and&#xD;
      launched in China in 2014 as a 3rd-line treatment for patients with advanced gastric cancer.&#xD;
      Therefore, investigators initialize this dose escalation phase I study to explore the safety&#xD;
      of combination of apatinib and POF as first-line treatment for advanced gastric cancer.&#xD;
      Investigators will analyze the maximum tolerated dose (MDT) and dose-limiting toxicity (DLT)&#xD;
      of apatinib in this study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Anticipated">June 30, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2018</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>Dose limiting toxicity</measure>
    <time_frame>From enrollment to completion of study. Estimated about 12 months.</time_frame>
    <description>Dose limiting toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum tolerance dose</measure>
    <time_frame>From enrollment to completion of study. Estimated about 12 months.</time_frame>
    <description>Maximum tolerance dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DTL reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>From enrollment to 3 months after treatment</time_frame>
    <description>Clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>From enrollment to progression of disease. Estimated about 6 months.</time_frame>
    <description>The length of time from enrollment until the time of progression of disease (PFS, progression-free survival).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From enrollment to death of patients. Estimated about 1 year.</time_frame>
    <description>The length of time from enrollment until the time of death (OS, overall survival).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">18</enrollment>
  <condition>Gastric Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Apatinib plus POF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This study will include a sequential evaluation of 3 subjects per cohort. Cohort 1: apatinib 250 mg per day and POF. Cohort 2: apatinib 375 mg per day and POF. Cohort 3: apatinib 500 mg per day and POF. Cohort 4: apatinib 625 mg per day and POF. Cohort 5: apatinib 750 mg per day and POF.&#xD;
A dose limiting toxicity (DLT) event is defined as any of the following events in the first 4-week period:&#xD;
CTCAE Grade 4 event (except for neutropenia lasting for ≤ 5 days);&#xD;
Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase)&#xD;
If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>Apatinib 250mg p.o. qd in first cohort (3 subjects). 375mg p.o. qd in second cohort (3 subjects). 500mg p.o. qd in third cohort (3 subjects). 625mg p.o. qd in forth cohort (3 subjects); 750mg p.o. qd in fifth cohort (3 subjects).&#xD;
Other Name:</description>
    <arm_group_label>Apatinib plus POF</arm_group_label>
    <other_name>YN968D1</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>POF</intervention_name>
    <description>The POF regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m2) followed by oxaliplatin (85 mg/m2) and Calcium Levofolinate (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days.</description>
    <arm_group_label>Apatinib plus POF</arm_group_label>
    <other_name>Paclitaxel plus Oxaliplatin plus Luecovorin plus 5-Fluorouracil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with advanced unresectable, histologically confirmed adenocarcinoma of the&#xD;
             gastric or gastroesophageal junction.&#xD;
&#xD;
          2. No previous treatment with chemotherapy or radiation therapy.&#xD;
&#xD;
          3. Ability to take medications orally.&#xD;
&#xD;
          4. With or without measurable lesions.&#xD;
&#xD;
          5. Patients must have a performance status of 0-1 on the Eastern Cooperative Oncology&#xD;
             Group (ECOG) scale.&#xD;
&#xD;
          6. Without serious system dysfunction and could tolerate chemotherapy. With normal&#xD;
             marrow, liver and renal function: a hemoglobin (HGB) of ≥100g/L (without blood&#xD;
             transfusion during 14 days); a leucopenia count of ≥4.0×109/L; a platelet count of&#xD;
             ≥100×109/L; a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL); a&#xD;
             creatinine (Cr) of ≤ 1.5 UNL; a creatinine clearance rate ≥ 50ml/min&#xD;
             (Cockcroft-Gault); a alanine aminotransferase (ALAT) and aspartate aminotransferase&#xD;
             (ASAT) of ≤2.5 UNL or ≤5 UNL in case of liver metastasis.&#xD;
&#xD;
          7. Life expectancy ≥3 months.&#xD;
&#xD;
          8. With normal electrocardiogram results and no history of congestive heart failure.&#xD;
&#xD;
          9. Without bleeding and thrombosis disease.&#xD;
&#xD;
         10. With normal coagulation function: activated partial thromboplastin time (APTT),&#xD;
             prothrombin time (PT) and INR, each ≤ 1.5 x ULN.&#xD;
&#xD;
         11. Female subjects of child-bearing potential must agree to use contraceptive measures&#xD;
             starting 1 week before the administration of the first dose of apatinib until 8 weeks&#xD;
             after discontinuing study drug. Male subjects must agree to use contraceptive measures&#xD;
             during the study and 8 weeks after last dose of study drug&#xD;
&#xD;
         12. With written informed consent signed voluntarily by patients themselves or their&#xD;
             supervisors witted by doctors.&#xD;
&#xD;
         13. With good compliance and agree to accept follow-up of disease progression and adverse&#xD;
             events.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with a history of another neoplastic disease within the past three years,&#xD;
             excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or&#xD;
             nonmetastatic prostate cancer.&#xD;
&#xD;
          2. Patients with brain or central nervous system metastases, including leptomeningeal&#xD;
             disease.&#xD;
&#xD;
          3. Pregnant (positive pregnancy test) or breast feeding.&#xD;
&#xD;
          4. Serious, non-healing wound, ulcer, or bone fracture.&#xD;
&#xD;
          5. Significant cardiac disease as defined as: unstable angina, New York Heart Association&#xD;
             (NYHA) grade II or greater, congestive heart failure, history of myocardial infarction&#xD;
             within 6 months Evidence of bleeding diathesis or coagulopathy.&#xD;
&#xD;
          6. History of a stroke or CVA within 6 months.&#xD;
&#xD;
          7. Clinically significant peripheral vascular disease.&#xD;
&#xD;
          8. Inability to comply with study and/or follow-up procedures.&#xD;
&#xD;
          9. Patients with any other medical condition or reason, in that investigator's opinion,&#xD;
             makes the patient unstable to participate in a clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rongbo Lin</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fujian Cancer Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Rongbo Lin</last_name>
    <phone>008613705919382</phone>
    <email>rongbo_lin@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Rongbo Lin</name>
      <address>
        <city>Fuzhou</city>
        <state>Fujian</state>
        <zip>350014</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rongbo Lin, MD</last_name>
      <phone>86+13705919382</phone>
      <email>rongbo_lin@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>July 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>January 24, 2018</last_update_submitted>
  <last_update_submitted_qc>January 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 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>Adenocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Apatinib</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/NCT03244774
org study id: FNF 007
nct id: NCT03244774
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
In previous studies, we found that POF (A combination of oxaliplatin, fluorouracil and
      Paclitaxel) regimen appears to be of good efficacy and is well tolerated in patients with
      advanced gastric cancer. Apatinib is an orally antiangiogenic agent. It was approved and
      launched in China in 2014 as a 3rd-line treatment for patients with advanced gastric cancer.
      Therefore, investigators initialize this dose escalation phase I study to explore the safety
      of combination of apatinib and POF as first-line treatment for advanced gastric cancer.
      Investigators will analyze the maximum tolerated dose (MDT) and dose-limiting toxicity (DLT)
      of apatinib in this study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose limiting toxicity
time frame: From enrollment to completion of study. Estimated about 12 months.
description: Dose limiting toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria
measure: Maximum tolerance dose
time frame: From enrollment to completion of study. Estimated about 12 months.
description: Maximum tolerance dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DTL reported.
measure: Objective response rate
time frame: From enrollment to 3 months after treatment
description: Clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate).
measure: Progression-free survival
time frame: From enrollment to progression of disease. Estimated about 6 months.
description: The length of time from enrollment until the time of progression of disease (PFS, progression-free survival).
measure: Overall survival
time frame: From enrollment to death of patients. Estimated about 1 year.
description: The length of time from enrollment until the time of death (OS, overall survival).
arm group label: Apatinib plus POF
arm group type: Experimental
description: This study will include a sequential evaluation of 3 subjects per cohort. Cohort 1: apatinib 250 mg per day and POF. Cohort 2: apatinib 375 mg per day and POF. Cohort 3: apatinib 500 mg per day and POF. Cohort 4: apatinib 625 mg per day and POF. Cohort 5: apatinib 750 mg per day and POF.
A dose limiting toxicity (DLT) event is defined as any of the following events in the first 4-week period:
CTCAE Grade 4 event (except for neutropenia lasting for ≤ 5 days);
Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase)
If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT.
intervention type: Drug
intervention name: Apatinib
description: Apatinib 250mg p.o. qd in first cohort (3 subjects). 375mg p.o. qd in second cohort (3 subjects). 500mg p.o. qd in third cohort (3 subjects). 625mg p.o. qd in forth cohort (3 subjects); 750mg p.o. qd in fifth cohort (3 subjects).
Other Name:
arm group label: Apatinib plus POF
other name: YN968D1
intervention type: Drug
intervention name: POF
description: The POF regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m2) followed by oxaliplatin (85 mg/m2) and Calcium Levofolinate (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days.
arm group label: Apatinib plus POF
other name: Paclitaxel plus Oxaliplatin plus Luecovorin plus 5-Fluorouracil
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Rongbo Lin
role: Principal Investigator
affiliation: Fujian Cancer Hospital
last name: Rongbo Lin
phone: 008613705919382
email: rongbo_lin@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Paclitaxel
mesh term: Fluorouracil
mesh term: Oxaliplatin
mesh term: Apatinib
sharing ipd: No