<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/NCT04483076</url>
  </required_header>
  <id_info>
    <org_study_id>RESONANCE-II</org_study_id>
    <nct_id>NCT04483076</nct_id>
  </id_info>
  <brief_title>Oxaliplatin Combined With S-1(SOX) Neoadjuvant Chemotherapy for Different Cycles in Patients With Gastric Cancer</brief_title>
  <acronym>RESONANCE-II</acronym>
  <official_title>A Prospective, Multicenter, Randomized, Controlled Phase III Study Evaluating Different Cycles of Oxaliplatin Combined With S-1 (SOX) as Neoadjuvant Chemotherapy for Patients With Locally Advanced Gastric Cancer: RESONANCE-II Trial</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study&#xD;
      which will enroll 524 patients in total. Patients with eligibility will be registered,&#xD;
      pre-enrolled and receive three cycles of SOX. Then, tumor response evaluation will be carried&#xD;
      out. Those who achieve stable disease or progressive disease will be excluded. Patients&#xD;
      achieving complete response or partial response will be enrolled and assigned into either&#xD;
      group A for another three cycles of SOX (six cycles in total) followed by D2 surgery and&#xD;
      group B for D2 surgery (three cycles in total). The primary endpoint is the rate of&#xD;
      pathological complete response and the secondary endpoints are R0 resection rate, three-year&#xD;
      disease-free survival, five-year overall survival and safety.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study&#xD;
      which was designed to evaluate the efficacy and safety of different cycles of SOX as&#xD;
      neoadjuvant chemotherapy for patients with locally advanced gastric cancer. All patients with&#xD;
      eligibility will be registered, pre-enrolled and receive three cycles of SOX. Then, tumor&#xD;
      response evaluation will be carried out according to the Response Evaluation Criteria for&#xD;
      Solid Tumors (RECIST) 1.1. Those who achieve stable disease (SD) or progressive disease&#xD;
      (PD)will be excluded. Patients achieving complete response (CR) or partial response (PR) will&#xD;
      be enrolled and assigned into either group A (six cycles of neoadjuvant chemotherapy with&#xD;
      SOX) for another three cycles of SOX followed by D2 surgery and group B (three cycles of&#xD;
      neoadjuvant chemotherapy with SOX) for D2 surgery. The primary endpoint is the rate of&#xD;
      pathological complete response (pCR%) and the secondary endpoints are R0 resection rate,&#xD;
      three-year disease-free survival (3-y DFS), five-year overall survival (5-y OS) and safety.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 13, 2021</start_date>
  <completion_date type="Anticipated">December 2028</completion_date>
  <primary_completion_date type="Anticipated">December 2022</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>pCR rate</measure>
    <time_frame>Postoperative, 2 years</time_frame>
    <description>The pCR rate is defined as the rate of patients achieving pCR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>R0 resection rate</measure>
    <time_frame>Postoperative, 2 years</time_frame>
    <description>The R0 resection rate is defined as the rate of R0 resection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Three-year disease-free survival</measure>
    <time_frame>From date of surgery until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 70 months</time_frame>
    <description>The DFS is defined as the period from the time of surgery to recurrence or death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Five-year overall survival</measure>
    <time_frame>From date of surgery until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 90 months</time_frame>
    <description>The OS is defined as the period from the time of surgery to death or last follow-up.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">524</enrollment>
  <condition>Gastric Cancer</condition>
  <condition>Chemotherapy Effect</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be pre-enrolled and receive three cycles of SOX. After randomization, patients in Arm A will receive three more cycles of SOX (six cycles of neoadjuvant chemotherapy with SOX in total) followed by D2 gastrectomy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will be pre-enrolled and receive three cycles of SOX. After randomization, patients in Arm B will receive D2 gastrectomy (three cycles of neoadjuvant chemotherapy with SOX in total).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chemotherapy drug</intervention_name>
    <description>The preoperative SOX chemotherapy consists of three-week cycles of intravenously administered oxaliplatin 130 mg/m2 on day 1 and orally administered S-1 40-60 mg twice a day (BID) on day 1 to 14. The dose of S-1 depends on body surface area (BSA): 40mg BID for BSA &lt; 1.25 m2; 50mg BID for 1.25 m2 &lt; BSA &lt;1.5 m2; 60mg BID for BSA &gt; 1.5 m2. Day 15 to day 21 is the rest period.</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Gastrectomy</intervention_name>
    <description>Surgery is planned 3-4 weeks after the last cycle of chemotherapy. A standard D2 radical laparoscopic gastrectomy is recommended. The extent of gastric resection and lymphadenectomy were performed as per the treatment guidelines. Reconstruction after gastrectomy was decided by the surgeon. All operations are performed by well trained and experienced surgical team to guarantee the quality of surgery, including harvesting more than 16 lymph nodes.</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Laparoscopic exploration</intervention_name>
    <description>Laparoscopic exploration is to detect occult peritoneal metastases and inspect the primary lesion, liver, diaphragm, pelvic organs, bowel and omentum according to the standard acquirements reported before. Patients with any patterns of distant metastases, suggestive of distant metastasis (M1), will be excluded from the trial.</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Non-bedridden, aged 18 to 70 years old;&#xD;
&#xD;
          2. Eastern Cooperative Oncology Group (ECOG) score is 0 to 1;&#xD;
&#xD;
          3. Histologically confirmed gastric adenocarcinoma;&#xD;
&#xD;
          4. Stage III (American Joint Committee on Cancer (AJCC) TNM staging system 8th edition)&#xD;
             gastric cancer confirmed by enhanced computer tomography (enhanced CT) and&#xD;
             laparoscopic exploration (endoscopic ultrasonography (EUS) and magnetic resonance&#xD;
             imaging (MRI) if necessary);&#xD;
&#xD;
          5. The research center and the surgeon have the ability to complete standard D2 radical&#xD;
             gastrectomy, and the gastrectomy can be tolerated by the patient;&#xD;
&#xD;
          6. Laboratory test criteria: peripheral blood hemoglobin (Hb) ≥ 90 g/L, neutrophil&#xD;
             absolute count ≥ 3×109 /L, platelet count (PLT) ≥ 100×109 /L, alanine aminotransferase&#xD;
             (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal&#xD;
             (ULN), total bilirubin ≤ 1.5×ULN, serum creatinine (SCr) ≤ 1.5×ULN, and serum albumin&#xD;
             (ALB) ≥ 30 g/L;&#xD;
&#xD;
          7. Patients with heart disease, the echocardiogram showed that the left ventricular&#xD;
             ejection fraction ≥ 50%, the electrocardiogram (ECG) is basically normal within 4&#xD;
             weeks before operation and without no obvious symptoms are acceptable;&#xD;
&#xD;
          8. There is no serious underlying disease that could lead to an expected life expectancy&#xD;
             &lt; 5 years;&#xD;
&#xD;
          9. Willing to sign the inform consent for participation and publication of results.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or lactating women;&#xD;
&#xD;
          2. Positive pregnancy test for women in childbearing age. Menopausal women without&#xD;
             menstruation for at least 12 months can be regarded as women with no possibility of&#xD;
             getting pregnant;&#xD;
&#xD;
          3. Refuse to birth control during the study;&#xD;
&#xD;
          4. Received any chemotherapy, radiotherapy or immunotherapy before;&#xD;
&#xD;
          5. History of other malignant diseases in the last five years (except for cervical&#xD;
             carcinoma in situ);&#xD;
&#xD;
          6. History of uncontrolled central nervous system diseases, which could influence the&#xD;
             compliance;&#xD;
&#xD;
          7. History of severe liver diseases, renal diseases or respiratory diseases; Uncontrolled&#xD;
             diabetes and hypertension; Clinically severe heart disease, such as congestive heart&#xD;
             failure, symptomatic coronary heart disease, uncontrolled arrhythmia, or a history of&#xD;
             myocardial infarction in the last six months;&#xD;
&#xD;
          8. History of dysphagia, complete or partial gastrointestinal obstruction, active&#xD;
             gastrointestinal bleeding and gastrointestinal perforation;&#xD;
&#xD;
          9. On steroid treatment after organ transplant;&#xD;
&#xD;
         10. With uncontrolled severe infections;&#xD;
&#xD;
         11. Known dihydropyrimidine dehydrogenase deficiency (DPD);&#xD;
&#xD;
         12. Anaphylaxis to any research drug ingredient;&#xD;
&#xD;
         13. Known peripheral neuropathy (&gt; NCI-CTC AE 1). Patients with only disappearance of deep&#xD;
             tendon reflex need not to be excluded.&#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_contact>
    <last_name>Xinxin Wang, MD</last_name>
    <phone>+8613811858199</phone>
    <email>301wxx@sina.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Chinese PLA General Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100853</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xinxin Wang, Dr.</last_name>
      <phone>+8613811858199</phone>
      <email>301wxx@sina.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 19, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>January 17, 2021</last_update_submitted>
  <last_update_submitted_qc>January 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 20, 2021</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>Prof.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Neoplasms</mesh_term>
  </condition_browse>
  <!-- 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/NCT04483076
org study id: RESONANCE-II
nct id: NCT04483076
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study
      which will enroll 524 patients in total. Patients with eligibility will be registered,
      pre-enrolled and receive three cycles of SOX. Then, tumor response evaluation will be carried
      out. Those who achieve stable disease or progressive disease will be excluded. Patients
      achieving complete response or partial response will be enrolled and assigned into either
      group A for another three cycles of SOX (six cycles in total) followed by D2 surgery and
      group B for D2 surgery (three cycles in total). The primary endpoint is the rate of
      pathological complete response and the secondary endpoints are R0 resection rate, three-year
      disease-free survival, five-year overall survival and safety.
RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study
      which was designed to evaluate the efficacy and safety of different cycles of SOX as
      neoadjuvant chemotherapy for patients with locally advanced gastric cancer. All patients with
      eligibility will be registered, pre-enrolled and receive three cycles of SOX. Then, tumor
      response evaluation will be carried out according to the Response Evaluation Criteria for
      Solid Tumors (RECIST) 1.1. Those who achieve stable disease (SD) or progressive disease
      (PD)will be excluded. Patients achieving complete response (CR) or partial response (PR) will
      be enrolled and assigned into either group A (six cycles of neoadjuvant chemotherapy with
      SOX) for another three cycles of SOX followed by D2 surgery and group B (three cycles of
      neoadjuvant chemotherapy with SOX) for D2 surgery. The primary endpoint is the rate of
      pathological complete response (pCR%) and the secondary endpoints are R0 resection rate,
      three-year disease-free survival (3-y DFS), five-year overall survival (5-y OS) and safety.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: pCR rate
time frame: Postoperative, 2 years
description: The pCR rate is defined as the rate of patients achieving pCR.
measure: R0 resection rate
time frame: Postoperative, 2 years
description: The R0 resection rate is defined as the rate of R0 resection.
measure: Three-year disease-free survival
time frame: From date of surgery until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 70 months
description: The DFS is defined as the period from the time of surgery to recurrence or death.
measure: Five-year overall survival
time frame: From date of surgery until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 90 months
description: The OS is defined as the period from the time of surgery to death or last follow-up.
arm group label: Arm A
arm group type: Experimental
description: Patients will be pre-enrolled and receive three cycles of SOX. After randomization, patients in Arm A will receive three more cycles of SOX (six cycles of neoadjuvant chemotherapy with SOX in total) followed by D2 gastrectomy.
arm group label: Arm B
arm group type: Active Comparator
description: Patients will be pre-enrolled and receive three cycles of SOX. After randomization, patients in Arm B will receive D2 gastrectomy (three cycles of neoadjuvant chemotherapy with SOX in total).
intervention type: Drug
intervention name: Chemotherapy drug
description: The preoperative SOX chemotherapy consists of three-week cycles of intravenously administered oxaliplatin 130 mg/m2 on day 1 and orally administered S-1 40-60 mg twice a day (BID) on day 1 to 14. The dose of S-1 depends on body surface area (BSA): 40mg BID for BSA < 1.25 m2; 50mg BID for 1.25 m2 < BSA <1.5 m2; 60mg BID for BSA > 1.5 m2. Day 15 to day 21 is the rest period.
arm group label: Arm A
arm group label: Arm B
intervention type: Procedure
intervention name: Gastrectomy
description: Surgery is planned 3-4 weeks after the last cycle of chemotherapy. A standard D2 radical laparoscopic gastrectomy is recommended. The extent of gastric resection and lymphadenectomy were performed as per the treatment guidelines. Reconstruction after gastrectomy was decided by the surgeon. All operations are performed by well trained and experienced surgical team to guarantee the quality of surgery, including harvesting more than 16 lymph nodes.
arm group label: Arm A
arm group label: Arm B
intervention type: Procedure
intervention name: Laparoscopic exploration
description: Laparoscopic exploration is to detect occult peritoneal metastases and inspect the primary lesion, liver, diaphragm, pelvic organs, bowel and omentum according to the standard acquirements reported before. Patients with any patterns of distant metastases, suggestive of distant metastasis (M1), will be excluded from the trial.
arm group label: Arm A
arm group label: Arm B
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Xinxin Wang, MD
phone: +8613811858199
email: 301wxx@sina.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Chinese PLA General Hospital
investigator full name: Lin Chen
investigator title: Prof.
mesh term: Stomach Neoplasms