<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/NCT03013010</url>
  </required_header>
  <id_info>
    <org_study_id>FUSCC-LAGCCS002</org_study_id>
    <nct_id>NCT03013010</nct_id>
  </id_info>
  <brief_title>PREACT Study: Locally Advanced Gastric Cancer, Chemoradiotherapy vs. Chemotherapy Followed by D2 Surgery and Adjuvant Chemotherapy</brief_title>
  <acronym>PREACT</acronym>
  <official_title>A Randomized, Controlled, Multicenter Study to Compare Preoperative Radiochemotherapy With Preoperative Chemotherapy in Patients With Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma (PREACT Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Cancer Hospital, China</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ruijin Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Xinhua Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Huadong Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai Cancer Hospital, China</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Although the incidence of gastric cancer has been substantially declining for several&#xD;
      decades, it is still the sixth most common cancer and the fourth most frequent cause of&#xD;
      cancer death worldwide. Surgery is still the only curative option for gastric cancer.&#xD;
      However, most patients are unable to undergo surgery because of late stage, unresectable&#xD;
      disease. The prognosis for these patients is very poor. Although the Magic trial showed that&#xD;
      perioperative chemotherapy can increase the rate of curative surgery and significantly&#xD;
      improve overall survival in patients with operable gastric or lower esophageal&#xD;
      adenocarcinomas, no pCR events were reported in this trial. The intervention arm in PREACT&#xD;
      consists of pre-operative chemotherapy, pre-operative radiochemotherapy, surgery and&#xD;
      post-operative chemotherapy. The control arm consists of pre-operative chemotherapy, surgery,&#xD;
      and post-operative chemotherapy. The primary purpose of PREACT is to investigate whether the&#xD;
      addition of radiochemotherapy to chemotherapy is superior to chemotherapy alone in the&#xD;
      pre-operative setting in improving disease free survival in patients with locally advanced&#xD;
      gastric or esophagogastric junction adenocarcinoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Disease free survival</measure>
    <time_frame>up to 3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical complete resection rate (R0)</measure>
    <time_frame>at the time of surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathological response rate</measure>
    <time_frame>at the time of surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with toxicities</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with surgery-related complication</measure>
    <time_frame>at the time of surgery</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">682</enrollment>
  <condition>Stomach Neoplasm</condition>
  <condition>GastroEsophageal Cancer</condition>
  <condition>Adenocarcinoma</condition>
  <condition>Locally Advanced Cancer</condition>
  <condition>Chemoradiation</condition>
  <arm_group>
    <arm_group_label>Preoperative radiochemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 cycle preoperative chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin.&#xD;
5 weeks preoperative chemoradiotherapy.&#xD;
1 cycle preoperative chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin.&#xD;
Gastric resection. 3 cycles adjuvant chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Preoperative chemotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>3 cycles preoperative chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin.&#xD;
Gastric resection. 3 cycles adjuvant chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tegafur-Gimeracil-Oteracil Potassium</intervention_name>
    <description>The dose of S-1 is according to body-surface area (BSA): patients with a BSA of less than 1.25 m2 received 80 mg daily; those with a BSA of 1.25 m2 or more but less than 1.5 m2 received 100 mg daily; and those with a BSA of 1.5 m2 or more received 120 mg daily. oxaliplatin 130mg/m2, intravenously, on day 1.</description>
    <arm_group_label>Preoperative chemotherapy</arm_group_label>
    <arm_group_label>Preoperative radiochemotherapy</arm_group_label>
    <other_name>S-1</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Chemoradiotherapy</intervention_name>
    <description>Chemotherapy: S-1 40-60mg/m2 orally, oral tablet twice daily, days 1-5 of each week of radiotherapy.&#xD;
Radiotherapy: 45 Gy of radiation in 25 fractions, five days per week for five weeks.</description>
    <arm_group_label>Preoperative radiochemotherapy</arm_group_label>
    <other_name>radiochemotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Gastric resection</intervention_name>
    <description>A standard D2 gastrectomy was recommended. The type of gastrectomy performed depended on the location and extent of the primary lesion. For middle third tumors, the gastric margin was recommended to be more than 5 cm, and a total gastrectomy was performed. For lower third tumors, a 2 cm duodenal margin was recommended and a subtotal or total gastrectomy was considered. For upper third tumors, a 3 cm esophageal margin was recommended and a total gastrectomy or esophagogastrectomy was performed. Billroth I or Roux-en-y gastrojejunostomy was performed for distal gastrectomy patients, Roux-en-y esophagojejunostomy was performed for total gastrectomy patients.</description>
    <arm_group_label>Preoperative chemotherapy</arm_group_label>
    <arm_group_label>Preoperative radiochemotherapy</arm_group_label>
    <other_name>Gastrectomy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>The dose of oxaliplatin is according to body-surface area (BSA): 130mg/m2, intravenously, on day 1.</description>
    <arm_group_label>Preoperative chemotherapy</arm_group_label>
    <arm_group_label>Preoperative radiochemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;=18 years&#xD;
&#xD;
          -  Female and male&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1&#xD;
&#xD;
          -  Life expectancy &gt;=6 months&#xD;
&#xD;
          -  Histologically proven adenocarcinoma of the stomach or gastroesophageal junction (GEJ)&#xD;
             (excluding Siewert I) that is: Stage IIB (T3N1 only), IIIA (T2N3 not eligible), IIIB,&#xD;
             and IIIC, i.e. T3 - T4a and node positive, or T4b and/ or node positive, according to&#xD;
             American Joint Committee on Cancer (AJCC) 7th edition&#xD;
&#xD;
          -  Considered operable following initial staging investigations or after pre-operative&#xD;
             therapy Disease which can be radically treated with radiotherapy to 45 Gy with&#xD;
             standard fractionation&#xD;
&#xD;
          -  Adequate organ function defined as follows:&#xD;
&#xD;
          -  Bone marrow: Haemoglobin &gt;=90 g/L, Absolute neutrophil count (ANC) &gt;=1.5 x 109 /L,&#xD;
             Platelet count &gt;=100 x 109 /L; Hepatic: Serum bilirubin &lt;=1.5 x upper limit of normal,&#xD;
             aspartate aminotransferase (AST) and/or alanine transaminase (ALT) &lt;=2.5 x upper limit&#xD;
             of normal; Renal: Serum creatinine &lt;=1.0 x upper limit of normal&#xD;
&#xD;
          -  Patients are willing to obey the treatment and provide blood and tissue specimens&#xD;
&#xD;
          -  Written informed consent obtained before randomization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating females or female patients of childbearing potential who have&#xD;
             not been surgically sterilized or are without adequate contraceptive measures&#xD;
&#xD;
          -  Sexually active males or females refuse to practice contraception during the study&#xD;
             until 30 days after end of study&#xD;
&#xD;
          -  Evidence of metastatic disease&#xD;
&#xD;
          -  Prior chemotherapy or radiotherapy&#xD;
&#xD;
          -  Patients with a past history of cancer in the 5 years before randomization except for&#xD;
             the squamous or basal cell carcinoma of the skin that has been effectively treated,&#xD;
             and carcinoma in situ of the cervix that has been treated by operation&#xD;
&#xD;
          -  Patients with other significant underlying medical conditions that may be aggravated&#xD;
             by the study treatment or are not controlled&#xD;
&#xD;
          -  Patients with central nervous system(CNS) disorder or peripheral nervous system&#xD;
             disorder or psychiatric disease&#xD;
&#xD;
          -  Known history of uncontrolled or symptomatic angina, uncontrolled arrhythmias and&#xD;
             hypertension, or congestive heart failure, or cardiac infarction within 6 months prior&#xD;
             to study enrollment, or cardiac insufficiency&#xD;
&#xD;
          -  Concurrent severe infection&#xD;
&#xD;
          -  Severe gastrointestinal bleeding, gastrointestinal perforation&#xD;
&#xD;
          -  Unable to swallow&#xD;
&#xD;
          -  Concurrent disease or condition that would make the subject inappropriate for study&#xD;
             participation or any serious medical disorder that would interfere with the subject's&#xD;
             safety&#xD;
&#xD;
          -  Known hypersensitivity reaction or metabolic disorder to S-1or oxaliplatin&#xD;
&#xD;
          -  Renal impairment (GFR &lt;=50ml/min)&#xD;
&#xD;
          -  Linitis plastica&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ya-nong Wang, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Zhen Zhang, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zhen Zhang, M.D.</last_name>
    <phone>(86)13661738625</phone>
    <email>Zhenzhang6@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xiao-wen Liu, M.D.</last_name>
    <phone>(86)13636698200</phone>
    <email>liuxw1129@hotmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhen Zhang, M.D.</last_name>
      <phone>(86)13661738625</phone>
      <email>zhenzhang6@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Xiaowen Liu, M.D.</last_name>
      <phone>(86)13636698200</phone>
      <email>liuxw1129@hotmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>July 2, 2020</last_update_submitted>
  <last_update_submitted_qc>July 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Randomized</keyword>
  <keyword>Open Label</keyword>
  <keyword>Multicenter</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <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>Tegafur</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</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/NCT03013010
org study id: FUSCC-LAGCCS002
nct id: NCT03013010
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Although the incidence of gastric cancer has been substantially declining for several
      decades, it is still the sixth most common cancer and the fourth most frequent cause of
      cancer death worldwide. Surgery is still the only curative option for gastric cancer.
      However, most patients are unable to undergo surgery because of late stage, unresectable
      disease. The prognosis for these patients is very poor. Although the Magic trial showed that
      perioperative chemotherapy can increase the rate of curative surgery and significantly
      improve overall survival in patients with operable gastric or lower esophageal
      adenocarcinomas, no pCR events were reported in this trial. The intervention arm in PREACT
      consists of pre-operative chemotherapy, pre-operative radiochemotherapy, surgery and
      post-operative chemotherapy. The control arm consists of pre-operative chemotherapy, surgery,
      and post-operative chemotherapy. The primary purpose of PREACT is to investigate whether the
      addition of radiochemotherapy to chemotherapy is superior to chemotherapy alone in the
      pre-operative setting in improving disease free survival in patients with locally advanced
      gastric or esophagogastric junction adenocarcinoma.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease free survival
time frame: up to 3 years
measure: Overall survival
time frame: up to 3 years
measure: Surgical complete resection rate (R0)
time frame: at the time of surgery
measure: Pathological response rate
time frame: at the time of surgery
measure: Proportion of patients with toxicities
time frame: up to 3 years
measure: Proportion of patients with surgery-related complication
time frame: at the time of surgery
arm group label: Preoperative radiochemotherapy
arm group type: Experimental
description: 1 cycle preoperative chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin.
5 weeks preoperative chemoradiotherapy.
1 cycle preoperative chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin.
Gastric resection. 3 cycles adjuvant chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin.
arm group label: Preoperative chemotherapy
arm group type: Active Comparator
description: 3 cycles preoperative chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin.
Gastric resection. 3 cycles adjuvant chemotherapy with S-1(Tegafur-Gimeracil-Oteracil Potassium)+ oxaliplatin.
intervention type: Drug
intervention name: Tegafur-Gimeracil-Oteracil Potassium
description: The dose of S-1 is according to body-surface area (BSA): patients with a BSA of less than 1.25 m2 received 80 mg daily; those with a BSA of 1.25 m2 or more but less than 1.5 m2 received 100 mg daily; and those with a BSA of 1.5 m2 or more received 120 mg daily. oxaliplatin 130mg/m2, intravenously, on day 1.
arm group label: Preoperative chemotherapy
arm group label: Preoperative radiochemotherapy
other name: S-1
intervention type: Radiation
intervention name: Chemoradiotherapy
description: Chemotherapy: S-1 40-60mg/m2 orally, oral tablet twice daily, days 1-5 of each week of radiotherapy.
Radiotherapy: 45 Gy of radiation in 25 fractions, five days per week for five weeks.
arm group label: Preoperative radiochemotherapy
other name: radiochemotherapy
intervention type: Procedure
intervention name: Gastric resection
description: A standard D2 gastrectomy was recommended. The type of gastrectomy performed depended on the location and extent of the primary lesion. For middle third tumors, the gastric margin was recommended to be more than 5 cm, and a total gastrectomy was performed. For lower third tumors, a 2 cm duodenal margin was recommended and a subtotal or total gastrectomy was considered. For upper third tumors, a 3 cm esophageal margin was recommended and a total gastrectomy or esophagogastrectomy was performed. Billroth I or Roux-en-y gastrojejunostomy was performed for distal gastrectomy patients, Roux-en-y esophagojejunostomy was performed for total gastrectomy patients.
arm group label: Preoperative chemotherapy
arm group label: Preoperative radiochemotherapy
other name: Gastrectomy
intervention type: Drug
intervention name: Oxaliplatin
description: The dose of oxaliplatin is according to body-surface area (BSA): 130mg/m2, intravenously, on day 1.
arm group label: Preoperative chemotherapy
arm group label: Preoperative radiochemotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ya-nong Wang, M.D.
role: Principal Investigator
affiliation: Fudan University
last name: Zhen Zhang, M.D.
role: Principal Investigator
affiliation: Fudan University
last name: Zhen Zhang, M.D.
phone: (86)13661738625
email: Zhenzhang6@gmail.com
last name: Xiao-wen Liu, M.D.
phone: (86)13636698200
email: liuxw1129@hotmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Stomach Neoplasms
mesh term: Oxaliplatin
mesh term: Tegafur
sharing ipd: Yes