<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/NCT03007446</url>
  </required_header>
  <id_info>
    <org_study_id>Ahead-BG301</org_study_id>
    <nct_id>NCT03007446</nct_id>
  </id_info>
  <brief_title>The Study of Conversion Surgery for Apatinib in Combination With SOX for Patients With Unresectable Gastric Cancer</brief_title>
  <official_title>The Exploratory Study of Conversion Surgery for Apatinib in Combination With Oxaliplatin/S-1(SOX) for Patients With Unresectable Gastric Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chinese PLA General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chinese PLA General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Prospective，Single-center，Single-arm，Open-label exploratory clinical trial&#xD;
      evaluating the efficacy and safety of Conversion Surgery for Apatinib plus SOX for patients&#xD;
      with unresectable gastric cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Gastric cancer is the second most common cause of cancer-related deaths worldwide, and&#xD;
      surgical resection during the early stage has improved treatment outcomes.However, many&#xD;
      patients are diagnosed with unresectable advanced or metastatic stage disease losing the&#xD;
      radical surgery opportunity. Systemic chemotherapy is the leading treatment that prolongs&#xD;
      survival times for such patients.&#xD;
&#xD;
      Approximate 20 patients with unresectable gastric cancer will be enrolled in this study,the&#xD;
      investigators will evaluate the efficacy and security of Apatinib + SOX(oxaliplatin+S-1) for&#xD;
      unresectable gastric cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>November 2016</start_date>
  <completion_date type="Anticipated">November 2018</completion_date>
  <primary_completion_date type="Anticipated">November 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>reaction rate</measure>
    <time_frame>4 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>an expected average of 6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival</measure>
    <time_frame>an expected average of 6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival</measure>
    <time_frame>an expected average of 6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>adverse events</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Gastric Cancer</condition>
  <arm_group>
    <arm_group_label>Apatinib plus Oxaliplatin/S-1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Apatinib :&#xD;
A starting dose of apatinib was administered 500 mg daily on days 1 through 21 of each 3-week cycle.&#xD;
Oxaliplatin:130 mg/m2，d1，ivgtt，in a 21 day cycle.&#xD;
S-1:40mg，bid，d1-14，po，in a 21 day cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>Apatinib :A starting dose of apatinib was administered 500 mg daily</description>
    <arm_group_label>Apatinib plus Oxaliplatin/S-1</arm_group_label>
    <other_name>Apatinib mesylate tablets</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Oxaliplatin:130 mg/m2，d1，ivgtt，in a 21 day cycle</description>
    <arm_group_label>Apatinib plus Oxaliplatin/S-1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>S-1</intervention_name>
    <description>S-1:40mg，bid，d1-14，po，in a 21 day cycle.</description>
    <arm_group_label>Apatinib plus Oxaliplatin/S-1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically proved gastric adenocarcinoma;&#xD;
&#xD;
          2. At least a unresectable factor before operation via CT, MRI, or PET-CT: difficult&#xD;
             resection of locally advanced gastric cancer(T4b); hepatic metastasis (H1; at most&#xD;
             five lesions, total diameter ≤8 cm); Peritoneal metastasis(CY1, P1) ;&#xD;
&#xD;
          3. Definitely diagnosed as unresectable gastric cancer via exploratory laparoscopy or&#xD;
             laparotomy;&#xD;
&#xD;
          4. ECOG performance status 0-2;&#xD;
&#xD;
          5. Age 18-70 years old, Life expectancy estimated than 3 months;&#xD;
&#xD;
          6. For results of blood routine test and biochemical tests:&#xD;
&#xD;
               1. Hgb ≥ 80g/L,&#xD;
&#xD;
               2. WBC ≥ 4000/mm3,&#xD;
&#xD;
               3. ANC ≥ 1.5×109/L,&#xD;
&#xD;
               4. platelets ≥ 80×109/L&#xD;
&#xD;
               5. ALT and AST ≤ 2.5 x upper normal limit (UNL), and ≤ 5 x UNL（Hematogenous&#xD;
                  metastases）,&#xD;
&#xD;
               6. Serum Total bilirubin ≤ 1.5 X UNL,&#xD;
&#xD;
               7. Serum Creatine ≤ 1.5 x UNL ；&#xD;
&#xD;
          7. Good cardiac function before the recruitment, no seizure of myocardial infarction in&#xD;
             past half years, and controllable hypertension and other coronary heart disease;&#xD;
&#xD;
          8. Not concomitant with other uncontrollable benign disease before the recruitment(e.g.&#xD;
             the infection in the kidney, lung and liver);&#xD;
&#xD;
          9. informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with poor-controlled arterial hypertension (systolic blood pressure&gt; 140 mmHg&#xD;
             and diastolic blood pressure &gt; 90 mm Hg) despite standard medical management; Coronary&#xD;
             heart disease greater than Class I; I-level arrhythmia (including QT interval&#xD;
             prolongation, for man ≥ 450 ms, for woman ≥ 470 ms) together with Class I cardiac&#xD;
             dysfunction; Patients with positive urinary protein;&#xD;
&#xD;
          2. Factors that could have an effect on oral medication (such as inability to swallow,&#xD;
             chronic diarrhea and intestinal obstruction);&#xD;
&#xD;
          3. Subjects with high gastrointestinal bleeding risk, including the following conditions:&#xD;
             local active ulcer lesions with positive fecal occult blood test (++); history of&#xD;
             black stool, or vomiting blood in the past 2 months;&#xD;
&#xD;
          4. Contraindications include allergy to apatinib and/or its accessories, active bleeding,&#xD;
             intestinal perforation, intestinal obstruction, within 30 days after surgery, drugs&#xD;
             with poor-controlled hypertension, Class Ⅲ-Ⅳ cardiac dysfunction （NYHA standard）,&#xD;
             severe hepatic and renal dysfunction（level 4）if apatinib use is considered;&#xD;
&#xD;
          5. Abnormal Coagulation (INR&gt;1.5, APTT&gt;1.5 UNL), with tendency of bleed;&#xD;
&#xD;
          6. Pregnant or lactating women;&#xD;
&#xD;
          7. Any other condition that might place the patient at undue risk or preclude a patient&#xD;
             from completing the study;&#xD;
&#xD;
          8. Treatment with prior radiotherapy, chemotherapy, Targeted therapy or immunotherapy;&#xD;
&#xD;
          9. Other conditions regimented at investigators' discretion.&#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>Lin Chen</last_name>
    <role>Principal Investigator</role>
    <affiliation>the Chinese PLA General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hongqing Xi, Master</last_name>
    <phone>010-66938128</phone>
  </overall_contact>
  <location>
    <facility>
      <name>the chinese PLA General Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100853</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lin Chen, Master</last_name>
      <phone>13801290395</phone>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, Dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-39. doi: 10.1016/S0140-6736(13)61719-5. Epub 2013 Oct 3.</citation>
    <PMID>24094768</PMID>
  </reference>
  <reference>
    <citation>Fukuchi M, Ishiguro T, Ogata K, Suzuki O, Kumagai Y, Ishibashi K, Ishida H, Kuwano H, Mochiki E. Prognostic Role of Conversion Surgery for Unresectable Gastric Cancer. Ann Surg Oncol. 2015 Oct;22(11):3618-24. doi: 10.1245/s10434-015-4422-6. Epub 2015 Feb 7.</citation>
    <PMID>25663597</PMID>
  </reference>
  <reference>
    <citation>Kanda T, Yajima K, Kosugi S, Ishikawa T, Ajioka Y, Hatakeyama K. Gastrectomy as a secondary surgery for stage IV gastric cancer patients who underwent S-1-based chemotherapy: a multi-institute retrospective study. Gastric Cancer. 2012 Jul;15(3):235-44. doi: 10.1007/s10120-011-0100-y. Epub 2011 Oct 28.</citation>
    <PMID>22033890</PMID>
  </reference>
  <reference>
    <citation>Kitayama J, Ishigami H, Yamaguchi H, Yamashita H, Emoto S, Kaisaki S, Watanabe T. Salvage gastrectomy after intravenous and intraperitoneal paclitaxel (PTX) administration with oral S-1 for peritoneal dissemination of advanced gastric cancer with malignant ascites. Ann Surg Oncol. 2014 Feb;21(2):539-46. doi: 10.1245/s10434-013-3208-y. Epub 2013 Aug 22.</citation>
    <PMID>23975319</PMID>
  </reference>
  <reference>
    <citation>Inoue K, Nakane Y, Kogire M, Fujitani K, Kimura Y, Imamura H, Tamura S, Okano S, Kwon AH, Kurokawa Y, Shimokawa T, Takiuchi H, Tsujinaka T, Furukawa H. Phase II trial of preoperative S-1 plus cisplatin followed by surgery for initially unresectable locally advanced gastric cancer. Eur J Surg Oncol. 2012 Feb;38(2):143-9. doi: 10.1016/j.ejso.2011.11.009. Epub 2011 Dec 9.</citation>
    <PMID>22154885</PMID>
  </reference>
  <reference>
    <citation>Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. doi: 10.1200/JCO.2011.36.2236. Epub 2011 Aug 15.</citation>
    <PMID>21844504</PMID>
  </reference>
  <reference>
    <citation>Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y, Sun G, Yang Y, Wang L, Xu N, Cheng Y, Wang Z, Zheng L, Tao M, Zhu X, Ji D, Liu X, Yu H. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol. 2013 Sep 10;31(26):3219-25. doi: 10.1200/JCO.2013.48.8585. Epub 2013 Aug 5.</citation>
    <PMID>23918952</PMID>
  </reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <last_update_submitted>September 25, 2017</last_update_submitted>
  <last_update_submitted_qc>September 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chinese PLA General Hospital</investigator_affiliation>
    <investigator_full_name>Lin Chen</investigator_full_name>
    <investigator_title>Director of the General Surgery Department, Chinese PLA General Hospital</investigator_title>
  </responsible_party>
  <keyword>Apatinib</keyword>
  <keyword>SOX</keyword>
  <keyword>Conversion Surgery</keyword>
  <keyword>unresectable gastric cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT03007446
org study id: Ahead-BG301
nct id: NCT03007446
lead sponsor: 
has dmc: Yes
This is a Prospective，Single-center，Single-arm，Open-label exploratory clinical trial
      evaluating the efficacy and safety of Conversion Surgery for Apatinib plus SOX for patients
      with unresectable gastric cancer.
Gastric cancer is the second most common cause of cancer-related deaths worldwide, and
      surgical resection during the early stage has improved treatment outcomes.However, many
      patients are diagnosed with unresectable advanced or metastatic stage disease losing the
      radical surgery opportunity. Systemic chemotherapy is the leading treatment that prolongs
      survival times for such patients.

      Approximate 20 patients with unresectable gastric cancer will be enrolled in this study,the
      investigators will evaluate the efficacy and security of Apatinib + SOX(oxaliplatin+S-1) for
      unresectable gastric cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: reaction rate
time frame: 4 months
measure: Objective Response Rate
time frame: an expected average of 6 weeks
measure: Disease-free survival
time frame: an expected average of 6 weeks
measure: Progression-Free Survival
time frame: an expected average of 6 weeks
measure: Overall Survival
time frame: 3 years
measure: adverse events
time frame: 6 months
arm group label: Apatinib plus Oxaliplatin/S-1
arm group type: Experimental
description: Apatinib :
A starting dose of apatinib was administered 500 mg daily on days 1 through 21 of each 3-week cycle.
Oxaliplatin:130 mg/m2，d1，ivgtt，in a 21 day cycle.
S-1:40mg，bid，d1-14，po，in a 21 day cycle.
intervention type: Drug
intervention name: Apatinib
description: Apatinib :A starting dose of apatinib was administered 500 mg daily
arm group label: Apatinib plus Oxaliplatin/S-1
other name: Apatinib mesylate tablets
intervention type: Drug
intervention name: Oxaliplatin
description: Oxaliplatin:130 mg/m2，d1，ivgtt，in a 21 day cycle
arm group label: Apatinib plus Oxaliplatin/S-1
intervention type: Drug
intervention name: S-1
description: S-1:40mg，bid，d1-14，po，in a 21 day cycle.
arm group label: Apatinib plus Oxaliplatin/S-1
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Lin Chen
role: Principal Investigator
affiliation: the Chinese PLA General Hospital
last name: Hongqing Xi, Master
phone: 010-66938128
facility: 
status: Recruiting
contact: 
country: China
citation: Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, Dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-39. doi: 10.1016/S0140-6736(13)61719-5. Epub 2013 Oct 3.
PMID: 24094768
citation: Fukuchi M, Ishiguro T, Ogata K, Suzuki O, Kumagai Y, Ishibashi K, Ishida H, Kuwano H, Mochiki E. Prognostic Role of Conversion Surgery for Unresectable Gastric Cancer. Ann Surg Oncol. 2015 Oct;22(11):3618-24. doi: 10.1245/s10434-015-4422-6. Epub 2015 Feb 7.
PMID: 25663597
citation: Kanda T, Yajima K, Kosugi S, Ishikawa T, Ajioka Y, Hatakeyama K. Gastrectomy as a secondary surgery for stage IV gastric cancer patients who underwent S-1-based chemotherapy: a multi-institute retrospective study. Gastric Cancer. 2012 Jul;15(3):235-44. doi: 10.1007/s10120-011-0100-y. Epub 2011 Oct 28.
PMID: 22033890
citation: Kitayama J, Ishigami H, Yamaguchi H, Yamashita H, Emoto S, Kaisaki S, Watanabe T. Salvage gastrectomy after intravenous and intraperitoneal paclitaxel (PTX) administration with oral S-1 for peritoneal dissemination of advanced gastric cancer with malignant ascites. Ann Surg Oncol. 2014 Feb;21(2):539-46. doi: 10.1245/s10434-013-3208-y. Epub 2013 Aug 22.
PMID: 23975319
citation: Inoue K, Nakane Y, Kogire M, Fujitani K, Kimura Y, Imamura H, Tamura S, Okano S, Kwon AH, Kurokawa Y, Shimokawa T, Takiuchi H, Tsujinaka T, Furukawa H. Phase II trial of preoperative S-1 plus cisplatin followed by surgery for initially unresectable locally advanced gastric cancer. Eur J Surg Oncol. 2012 Feb;38(2):143-9. doi: 10.1016/j.ejso.2011.11.009. Epub 2011 Dec 9.
PMID: 22154885
citation: Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. doi: 10.1200/JCO.2011.36.2236. Epub 2011 Aug 15.
PMID: 21844504
citation: Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y, Sun G, Yang Y, Wang L, Xu N, Cheng Y, Wang Z, Zheng L, Tao M, Zhu X, Ji D, Liu X, Yu H. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol. 2013 Sep 10;31(26):3219-25. doi: 10.1200/JCO.2013.48.8585. Epub 2013 Aug 5.
PMID: 23918952
responsible party type: Principal Investigator
investigator affiliation: Chinese PLA General Hospital
investigator full name: Lin Chen
investigator title: Director of the General Surgery Department, Chinese PLA General Hospital
mesh term: Stomach Neoplasms
mesh term: Oxaliplatin
mesh term: Apatinib
sharing ipd: No