<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/NCT03751761</url>
  </required_header>
  <id_info>
    <org_study_id>AMC1803</org_study_id>
    <nct_id>NCT03751761</nct_id>
  </id_info>
  <brief_title>GC 2nd Line Durvalumab(MEDI4736)/Tremelimumab Plus Paclitaxel Study</brief_title>
  <official_title>Durvalumab(MEDI4736)/Tremelimumab Plus Paclitaxel in Patients With Metastatic Gastric Cancer After Failure of First-line Chemotherapy, Phase Ib/II</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Asan Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hallym University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Seoul National University Bundang Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Asan Medical Center</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>
      To evaluate safety and response rate of durvalumab/tremelimumab in combination with&#xD;
      paclitaxel in patients with metastatic gastric cancers who fail a first-line chemotherapy&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 11, 2018</start_date>
  <completion_date type="Anticipated">June 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</primary_completion_date>
  <phase>Phase 1/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>Safety based on NCI-CTCAE v4.03</measure>
    <time_frame>at least 4 weeks</time_frame>
    <description>Safety will be assessed in all patients who received at least one dose of study drugs based on NCI-CTCAE v4.03</description>
  </primary_outcome>
  <primary_outcome>
    <measure>response rate</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Response rate will be assessed by a team of independent reviewers based on RECIST v1.1.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>Metastatic Gastric Cancer</condition>
  <arm_group>
    <arm_group_label>durvalumab, tremelimumab, paclitaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>durvalumab, tremelimumab, paclitaxel</intervention_name>
    <description>Durvalumab, 1500 mg Q4W for 12 months Tremelimumab 75 mg Q4W for up to 4 doses/cycles Paclitaxel iv D1, D8, D15 Q4W (from 60mg/m2 to 80mg/m2)</description>
    <arm_group_label>durvalumab, tremelimumab, paclitaxel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent and any locally-required authorization obtained from the&#xD;
             subject prior to performing any protocol-related procedures, including screening&#xD;
             evaluations&#xD;
&#xD;
          2. Age &gt; 19 years at time of study entry or adult male or female (according to age of&#xD;
             majority as defined as ≥ 19 years)&#xD;
&#xD;
          3. Body weight &gt; 30kg&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1&#xD;
&#xD;
          5. Life expectancy of &gt; 12 weeks&#xD;
&#xD;
          6. Adequate normal organ and marrow function as defined below; Hemoglobin ≥ 9.0 g/dL&#xD;
             Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (&gt; 1,500 per mm3) Platelet count ≥ 100 x&#xD;
             109/L (&gt;100,000 per mm3) Serum bilirubin ≤ 1.5 x institutional upper limit of normal&#xD;
             (ULN). This will not apply to subjects with Gilbert's syndrome.&#xD;
&#xD;
             AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver&#xD;
             metastases are present, in which case it must be ≤ 5x ULN Serum creatinine CL&gt;40&#xD;
             mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine&#xD;
             collection for determination of creatinine clearance&#xD;
&#xD;
             Evidence of post-menopausal status or negative urinary or serum pregnancy test for&#xD;
             female pre-menopausal patients. Women will be considered post-menopausal if they have&#xD;
             been amenorrheic for 12 months without an alternative medical cause. The following&#xD;
             age-specific requirements apply&#xD;
&#xD;
          7. Subject is willing and able to comply with the protocol for the duration of the study&#xD;
             including undergoing treatment and scheduled visits and examinations including follow&#xD;
             up.&#xD;
&#xD;
          8. (for the phase II section) Have one of the following targeted sequencing results 1)&#xD;
             CD274 amplification 2) positive for mutations causing a hypermutation (PMS1, PMS2,&#xD;
             MLH1, MLH3, MSH2, MSH3, MSH6, POLD1, POLD2, or POLE) 3) microsatellite instability&#xD;
             (MSI high) 4) somatic exonic mutation rate-high 5) EBV positive&#xD;
&#xD;
          9. (for the phase II section) Have at least one investigator-assessed measurable disease&#xD;
             per RECIST v1.1&#xD;
&#xD;
         10. Have a histologically- or cytologically-confirmed gastric carcinoma&#xD;
&#xD;
         11. (for the phase II section) Have disease progression on or within 6 months of a&#xD;
             first-line fluoropyrimidine/platinum-containing chemotherapy for metastatic disease or&#xD;
             perioperative chemotherapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca&#xD;
             staff and/or staff at the study site)&#xD;
&#xD;
          2. Previous enrollment in the present study&#xD;
&#xD;
          3. Participation in another clinical study with an investigational product during the&#xD;
             last 2 weeks&#xD;
&#xD;
          4. (for the phase II section) Any previous treatment for metastatic disease with a PD1 or&#xD;
             PD-L1, including durvalumab inhibitor or an anti-CTLA4 including tremelimumab, or with&#xD;
             cancer vaccine, or with paclitaxel or docetaxel&#xD;
&#xD;
          5. History of another primary malignancy except for Malignancy treated with curative&#xD;
             intent and with no known active disease ≥ 5 years before the first dose of study drug&#xD;
             and of low potential risk for recurrence Adequately treated non-melanoma skin cancer&#xD;
             or lentigo maligna without evidence of disease Adequately treated carcinoma in situ&#xD;
             without evidence of disease eg, cervical cancer in situ&#xD;
&#xD;
          6. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,&#xD;
             endocrine therapy, targeted therapy including TKIs, tumor embolization, other&#xD;
             investigational agent) ≤ 2 weeks prior to the first dose of study drug (≤ 4 weeks&#xD;
             prior to the first dose of study drug for subjects who have received prior monoclonal&#xD;
             antibodies or biologic therapy, and within 6 weeks for nitrosourea or mitomycin C).&#xD;
&#xD;
          7. Any unresolved toxicity NCI-CTCAE Grade ≥2 from previous anticancer therapy with the&#xD;
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion&#xD;
             criteria; Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis&#xD;
             after consultation with the Study Physician. Patients with irreversible toxicity not&#xD;
             reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may&#xD;
             be included only after consultation with the Study Physician&#xD;
&#xD;
          8. Current or prior use of immunosuppressive medication within 14 days before the first&#xD;
             dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled&#xD;
             corticosteroids or systemic corticosteroids at physiological doses, which are not to&#xD;
             exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Dexamethasone used&#xD;
             for paclitaxel premedication is allowed.&#xD;
&#xD;
          9. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous&#xD;
             immunotherapy agent, or any unresolved irAE &gt;Grade 1&#xD;
&#xD;
         10. Active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease (eg, colitis or Crohn's disease), diverticulitis (with the&#xD;
             exception of diverticulosis), systemic lupus erythematosus, Sarcoidosis syndrome, or&#xD;
             Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid&#xD;
             arthritis, hypophysitis, uveitis, etc). The following are exceptions to this&#xD;
             criterion: Patients with vitiligo or alopecia, Patients with hypothyroidism (eg,&#xD;
             following Hashimoto syndrome) stable on hormone replacement, Any chronic skin&#xD;
             condition that does not require systemic therapy, Patients without active disease in&#xD;
             the last 5 years may be included but only after consultation with the study physician,&#xD;
             Patients with celiac disease controlled by diet alone.&#xD;
&#xD;
        11, History of primary immunodeficiency 12, History of allogeneic organ transplant 13.&#xD;
        History of hypersensitivity to durvalumab or tremelimumab 14. History of anaphylaxis&#xD;
        reactions to taxanes 15. Uncontrolled intercurrent illness including, but not limited to,&#xD;
        ongoing or active, symptomatic congestive heart failure, uncontrolled hypertension,&#xD;
        unstable angina pectoris, cardiac arrhythmia, active bleeding diatheses including any&#xD;
        subject known to have evidence of acute or chronic active hepatitis B or hepatitis C, or&#xD;
        psychiatric illness/social situations that would limit compliance with study requirements&#xD;
        or compromise the ability of the subject to give written informed consent 16. Active&#xD;
        infection including tuberculosis (clinical evaluation that includes clinical history,&#xD;
        physical examination and radiographic findings), hepatitis B (known positive HBV surface&#xD;
        antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2&#xD;
        antibodies). Patients with a past or resolved HBV infection (defined as the presence of&#xD;
        hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive&#xD;
        for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative&#xD;
        for HCV RNA 17. History of leptomeningeal carcinomatosis 18. Receipt of live attenuated&#xD;
        vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab&#xD;
        or tremelimumab 19. Female patients who are pregnant or breastfeeding or male or female&#xD;
        patients of reproductive potential who are not willing to employ effective birth control&#xD;
        from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after&#xD;
        the last dose of durvalumab + tremelimumab combination therapy 20. Any condition that, in&#xD;
        the opinion of the investigator, would interfere with evaluation of study treatment or&#xD;
        interpretation of patient safety or study results 21. Brain metastases or spinal cord&#xD;
        compression unless the patient is stable (asymptomatic; no evidence of new or emerging&#xD;
        brain metastases; and stable and off steroids and anti-convulsants for at least 14 days&#xD;
        prior to start of study treatment.&#xD;
&#xD;
        Patients with suspected brain metastases at screening should have an MRI (preferred) or CT&#xD;
        each preferably with IV contrast of the brain prior to study entry; Following radiotherapy&#xD;
        and/or surgery of the brain metastases patients must wait 4 weeks following the&#xD;
        intervention and before treatment with imaging to confirm stability 22. Subjects with&#xD;
        uncontrolled seizures. 23.Female patients who are pregnant or breastfeeding or male or&#xD;
        female patients of reproductive potential who are not willing to employ effective birth&#xD;
        control from screening to 180 days after the last dose of durvalumab, tremelimumab&#xD;
        combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is&#xD;
        the longer time period 24.Known allergy or hypersensitivity to IP or any excipient If a&#xD;
        patient withdraws from participation in the study, then his or her enrollment/randomization&#xD;
        code cannot be reused.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>138-736</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>November 21, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>December 30, 2022</last_update_submitted>
  <last_update_submitted_qc>December 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Asan Medical Center</investigator_affiliation>
    <investigator_full_name>Min-Hee Ryu</investigator_full_name>
    <investigator_title>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>Durvalumab</mesh_term>
    <mesh_term>Tremelimumab</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/NCT03751761
org study id: AMC1803
nct id: NCT03751761
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To evaluate safety and response rate of durvalumab/tremelimumab in combination with
      paclitaxel in patients with metastatic gastric cancers who fail a first-line chemotherapy
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety based on NCI-CTCAE v4.03
time frame: at least 4 weeks
description: Safety will be assessed in all patients who received at least one dose of study drugs based on NCI-CTCAE v4.03
measure: response rate
time frame: up to 12 months
description: Response rate will be assessed by a team of independent reviewers based on RECIST v1.1.
arm group label: durvalumab, tremelimumab, paclitaxel
arm group type: Experimental
intervention type: Drug
intervention name: durvalumab, tremelimumab, paclitaxel
description: Durvalumab, 1500 mg Q4W for 12 months Tremelimumab 75 mg Q4W for up to 4 doses/cycles Paclitaxel iv D1, D8, D15 Q4W (from 60mg/m2 to 80mg/m2)
arm group label: durvalumab, tremelimumab, paclitaxel
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Asan Medical Center
investigator full name: Min-Hee Ryu
investigator title: Professor
mesh term: Stomach Neoplasms
mesh term: Paclitaxel
mesh term: Durvalumab
mesh term: Tremelimumab
sharing ipd: No