<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/NCT03766607</url>
  </required_header>
  <id_info>
    <org_study_id>KSWOG 1018</org_study_id>
    <nct_id>NCT03766607</nct_id>
  </id_info>
  <brief_title>Trastuzumab Beyond Progression in HER2 Positive Metastatic Gastric Cancer</brief_title>
  <official_title>A Multi-center Phase II Study of Trastuzumab Biosimilar (SB3®) in Combination With Ramucirumab and Paclitaxel in HER2 Positive Metastatic Gastric Cancer Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Korean South West Oncology Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Korean South West Oncology Group</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>
      The aim of this study is to evaluate the efficacy and safety of combination therapy with&#xD;
      ramucirumab, paclitaxel, and trastuzumab biosimilar as second line treatment of HER2 positive&#xD;
      metastatic gastric cancer after failure of first line chemotherapy including trastuzumab.&#xD;
      This study is a phase II, single-arm, open label, multi-center study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Approximately 15% of patients with advanced gastric cancer have HER2 overexpression and the&#xD;
      combined use of trastuzumab and other cytotoxic chemotherapeutic agents, such as 5-FU and&#xD;
      cisplatin, in these patients is associated with a significantly improved survival rate&#xD;
      compared with cytotoxic chemotherapy alone. So, the combination of trastuzumab and&#xD;
      chemotherapy is currently being used as a standard treatment in HER2 positive advanced&#xD;
      gastric or gastroesophageal adenocarcinoma. However, after failing first line treatment with&#xD;
      such regimen, second line treatment is determined regardless of HER2 status, and the most&#xD;
      preferred treatment is ramucirumab and paclitaxel combination chemotherapy.&#xD;
&#xD;
      Recently, the use of trastuzumab in combination with other cytotoxic chemotherapeutic agents&#xD;
      has been reported to be superior to the use of cytotoxic chemotherapy alone in the treatment&#xD;
      of patients with HER2 positive metastatic breast cancer. On the basis of several guidelines,&#xD;
      it is recommended to extend the use of trastuzumab after disease progression. In addition, in&#xD;
      some retrospective studies of metastatic gastric cancer, it has been reported that treatment&#xD;
      with trastuzumab in combination with second line chemotherapy followed by first line&#xD;
      chemotherapy including trastuzumab is beneficial and it is worthwhile to be tested in the&#xD;
      prospective study. Furthermore, data on the safety and efficacy of cross-administration of&#xD;
      trastuzumab biosimilar have not been available yet.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Competing other studies&#xD;
  </why_stopped>
  <start_date type="Anticipated">September 30, 2019</start_date>
  <completion_date type="Anticipated">June 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</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>Progression free survival, PFS</measure>
    <time_frame>up to 12 months</time_frame>
    <description>as measured from the start of the treatment to the date of either documentation of disease progression or death</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate, ORR</measure>
    <time_frame>up to 6 months</time_frame>
    <description>defined as the proportion of subjects who have a best overall response of complete response or partial response as assessed by RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival, OS</measure>
    <time_frame>up to 12 months</time_frame>
    <description>defined as the time from the date of randomization until the date of death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse event</measure>
    <time_frame>up to 12 months</time_frame>
    <description>as measured by NCI-CTCAE v5.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Gastric Cancer</condition>
  <arm_group>
    <arm_group_label>Trastuzumab with Ramucirumab and Paclitaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single arm study of trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) every 21 days + ramucirumab (8 mg/kg) on days 1 &amp; 15 every 28 days + paclitaxel (80 mg/m2) on days 1, 8, and 15 every 28 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab</intervention_name>
    <description>Trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) administered intravenously every 21 days</description>
    <arm_group_label>Trastuzumab with Ramucirumab and Paclitaxel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ramucirumab</intervention_name>
    <description>Ramucirumab 8 mg/kg administered intravenously on days 1 and 15 every 28 days</description>
    <arm_group_label>Trastuzumab with Ramucirumab and Paclitaxel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Paclitaxel 80 mg/m2 administered intravenously on days 1, 8, and 15 every 28 days</description>
    <arm_group_label>Trastuzumab with Ramucirumab and Paclitaxel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Over 19 years old&#xD;
&#xD;
          2. Histologically confirmed HER2 overexpressing gastric cancer (HER2 overexpression is&#xD;
             defined as IHC 3+ or FISH +)&#xD;
&#xD;
          3. Metastatic gastric cancer&#xD;
&#xD;
          4. Progressive disease has been confirmed after first line treatment including&#xD;
             trastuzumab (If the recurrence occurred within 6 months after the completion of&#xD;
             postoperative adjuvant therapy, it can be considered as first line treatment.)&#xD;
&#xD;
          5. At least one measurable or evaluable lesion according to RECIST ver 1.1&#xD;
&#xD;
          6. ECOG performance status 0 or 1&#xD;
&#xD;
          7. Appropriate major organ function as defined below, A. Absolute neutrophil count (ANC)&#xD;
             ≥ 1,500/mm3 B. Platelet ≥ 100,000/mm3 C. Hemoglobin &gt; 8.0 g/dL D. Total bilirubin ≤&#xD;
             1.5 x ULN E. AST and ALT &lt; 3 x ULN (if there is a live metastasis, AST and ALT ≤ 5 x&#xD;
             ULN) F. Serum creatinine ≤ 1.5x ULN or CCr &gt; 50 mL/min&#xD;
&#xD;
          8. Life expectancy is more than 12 weeks&#xD;
&#xD;
          9. Echocardiography at the time of enrollment showed an ejection fraction ≥ 50%&#xD;
&#xD;
         10. Previous adverse events of chemotherapy or radiotherapy has been resolved to less than&#xD;
             grade 1 toxicity (exception: Alopecia, stable peripheral neuropathy, and manageable&#xD;
             electrolyte imbalance by replacement therapy are acceptable if they are resolved to&#xD;
             less than grade 2)&#xD;
&#xD;
         11. If the urine pregnancy test or serum beta-hCG result is negative in child bearing&#xD;
             women&#xD;
&#xD;
         12. If the subject have signed the informed consent form approved by the IRB&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Symptomatic or unstable CNS metastasis (exception: appropriately treated brain&#xD;
             metastasis without progression of more than 4 weeks after previous CT or MRI, and no&#xD;
             steroid treatment for symptom relief is necessary)&#xD;
&#xD;
          2. Active virus, bacteria, or fungal infection (exception: HBV DNA titer is in the normal&#xD;
             range for chronic hepatitis B carriers)&#xD;
&#xD;
          3. If previous chemotherapy or radiotherapy was applied within 3 weeks before the&#xD;
             administration of study drug&#xD;
&#xD;
          4. If the subject has received major surgery within 4 weeks and the recovery is not&#xD;
             complete before the administration of study drug&#xD;
&#xD;
          5. If there is a history of other malignancies within 3 years (exception: cervical&#xD;
             intraepithelial cancer, well differentiated thyroid cancer, or skin cancer has been&#xD;
             treated completely)&#xD;
&#xD;
          6. QTc interval &gt; 480 msec, long or short QT syndrome, or Burgada syndrome. In addition,&#xD;
             known prolongation of QTc interval or Torsade de Pointes&#xD;
&#xD;
          7. If there is a significant history of cardiovascular disease within 6 months, such as,&#xD;
             myocardial infarction, unstable angina, significant cardiac arrhythmia, and&#xD;
             uncontrolled hypertension (systolic BP &gt; 180 mmHg, diastolic BP &gt; 100 mmHg),&#xD;
             congestive heart failure (NYHA class III-IV), pericardial effusion or pericardial&#xD;
             tamponade, cardiomyopathy, cerebrovascular disease including transient ischemic&#xD;
             stroke, and symptomatic pulmonary embolism.&#xD;
&#xD;
          8. History of symptomatic interstitial pneumonia&#xD;
&#xD;
          9. History of other psychiatric problems, abnormalities of laboratory test which have&#xD;
             potential effects on administration of study drugs or participation on the study, or&#xD;
             if the subject is inappropriate to be participated according to the investigator's&#xD;
             decision (refusal to request and instruction, incooperative attitudes, etc.)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eun-Kee Song</last_name>
    <role>Principal Investigator</role>
    <affiliation>Korean Southwest Oncology Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chonbuk National University Hospital</name>
      <address>
        <city>Jeonju</city>
        <state>Jeollabuk-do</state>
        <zip>54907</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>September 17, 2019</last_update_submitted>
  <last_update_submitted_qc>September 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Korean South West Oncology Group</investigator_affiliation>
    <investigator_full_name>Hwan Jung Yun</investigator_full_name>
    <investigator_title>Clinical Professor</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Ramucirumab</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/NCT03766607
org study id: KSWOG 1018
nct id: NCT03766607
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to evaluate the efficacy and safety of combination therapy with
      ramucirumab, paclitaxel, and trastuzumab biosimilar as second line treatment of HER2 positive
      metastatic gastric cancer after failure of first line chemotherapy including trastuzumab.
      This study is a phase II, single-arm, open label, multi-center study.
Approximately 15% of patients with advanced gastric cancer have HER2 overexpression and the
      combined use of trastuzumab and other cytotoxic chemotherapeutic agents, such as 5-FU and
      cisplatin, in these patients is associated with a significantly improved survival rate
      compared with cytotoxic chemotherapy alone. So, the combination of trastuzumab and
      chemotherapy is currently being used as a standard treatment in HER2 positive advanced
      gastric or gastroesophageal adenocarcinoma. However, after failing first line treatment with
      such regimen, second line treatment is determined regardless of HER2 status, and the most
      preferred treatment is ramucirumab and paclitaxel combination chemotherapy.

      Recently, the use of trastuzumab in combination with other cytotoxic chemotherapeutic agents
      has been reported to be superior to the use of cytotoxic chemotherapy alone in the treatment
      of patients with HER2 positive metastatic breast cancer. On the basis of several guidelines,
      it is recommended to extend the use of trastuzumab after disease progression. In addition, in
      some retrospective studies of metastatic gastric cancer, it has been reported that treatment
      with trastuzumab in combination with second line chemotherapy followed by first line
      chemotherapy including trastuzumab is beneficial and it is worthwhile to be tested in the
      prospective study. Furthermore, data on the safety and efficacy of cross-administration of
      trastuzumab biosimilar have not been available yet.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival, PFS
time frame: up to 12 months
description: as measured from the start of the treatment to the date of either documentation of disease progression or death
measure: Objective response rate, ORR
time frame: up to 6 months
description: defined as the proportion of subjects who have a best overall response of complete response or partial response as assessed by RECIST 1.1
measure: Overall survival, OS
time frame: up to 12 months
description: defined as the time from the date of randomization until the date of death from any cause
measure: Adverse event
time frame: up to 12 months
description: as measured by NCI-CTCAE v5.0
arm group label: Trastuzumab with Ramucirumab and Paclitaxel
arm group type: Experimental
description: Single arm study of trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) every 21 days + ramucirumab (8 mg/kg) on days 1 & 15 every 28 days + paclitaxel (80 mg/m2) on days 1, 8, and 15 every 28 days
intervention type: Drug
intervention name: Trastuzumab
description: Trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) administered intravenously every 21 days
arm group label: Trastuzumab with Ramucirumab and Paclitaxel
intervention type: Drug
intervention name: Ramucirumab
description: Ramucirumab 8 mg/kg administered intravenously on days 1 and 15 every 28 days
arm group label: Trastuzumab with Ramucirumab and Paclitaxel
intervention type: Drug
intervention name: Paclitaxel
description: Paclitaxel 80 mg/m2 administered intravenously on days 1, 8, and 15 every 28 days
arm group label: Trastuzumab with Ramucirumab and Paclitaxel
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Eun-Kee Song
role: Principal Investigator
affiliation: Korean Southwest Oncology Group
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Korean South West Oncology Group
investigator full name: Hwan Jung Yun
investigator title: Clinical Professor
mesh term: Stomach Neoplasms
mesh term: Paclitaxel
mesh term: Trastuzumab
mesh term: Ramucirumab
sharing ipd: No