<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/NCT03764553</url>
  </required_header>
  <id_info>
    <org_study_id>2018_256</org_study_id>
    <nct_id>NCT03764553</nct_id>
  </id_info>
  <brief_title>Liposomal iRInotecan, Carboplatin or oXaliplatin for Esophagogastric Cancer</brief_title>
  <acronym>LyRICX</acronym>
  <official_title>Liposomal iRInotecan, Carboplatin or oXaliplatin in the First Line Treatment of Esophagogastric Cancer: a Randomized Phase 2 Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Servier</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multi-center, open label, randomized phase II trial for patients with previously&#xD;
      untreated metastatic or locally advanced esophagogastric cancer, using a pick the winner&#xD;
      design to identify the best combination therapy in terms of progression free survival and&#xD;
      neurotoxicity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The sample size to identify the best combination therapy is based on the following decision&#xD;
      making strategy. With less or even zero neurotoxicity grade 2-4 (defined as worst toxicity),&#xD;
      the Nal-IRI plus 5FU/LV (Fluorouracil/leucovorin)combination is expected to outperform the&#xD;
      standard combination capecitabine plus oxaliplatin and may also outperform capecitabine plus&#xD;
      carboplatin. To compensate for a higher neurotoxicity grade 2-4 level, the capecitabine&#xD;
      combinations should demonstrate increased progression free survival (PFS) according to the&#xD;
      next schedule.&#xD;
&#xD;
      Table 1. Decision making strategy&#xD;
&#xD;
      Difference in % neurotoxicity grade 2-4 Compensating Increase in PFS &gt;10 - 30% + 3 months &gt;30&#xD;
      - 50% + 4 months&#xD;
&#xD;
      The total number to be included will be 269. Patients will be randomized to respectively the&#xD;
      Nal-IRI plus 5FU, the capecitabine plus carboplatin and capecitabine plus oxaliplatin group&#xD;
      following a 2:2:1 scheme until 49 patients have been included in the capecitabine plus&#xD;
      oxaliplatin group and following a 1:1:0 scheme 10 afterwards for the remaining patients.&#xD;
      Taking into account 15% withdrawal of patients from the trial before start of study&#xD;
      medication, the investigators will include 310 patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 1, 2019</start_date>
  <completion_date type="Anticipated">August 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2024</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>phase 2 study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>42 months</time_frame>
    <description>To compare the progression free survival</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with treatment-related Neurotoxicity</measure>
    <time_frame>42 months</time_frame>
    <description>Number of participants with treatment-related Neurotoxicity according to CTCAE v4.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>54 months</time_frame>
    <description>To determine the overall survival of F-Nal-IRI, capecitabine/Carboplatin (CapCar) and capecitabine/oxaliplatin (CapOx)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>response rate</measure>
    <time_frame>42 months</time_frame>
    <description>To determine the response rate of F-Nal-IRI, CapCar and CapOx</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>adverse events</measure>
    <time_frame>42 months</time_frame>
    <description>To determine the adverse events of F-Nal-IRI, CapCar and CapOx according to NCI common toxicity criteria (CTC) version 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ C30))</measure>
    <time_frame>42 months</time_frame>
    <description>Overall Quality of life ranging from 0-100 with 100 being best Quality of Life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>percentage subsequent treatment lines</measure>
    <time_frame>42 months</time_frame>
    <description>The percentage of patients proceeding to subsequent lines of treatment after progression and describe the types of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the reasons for forgoing subsequent treatment</measure>
    <time_frame>42 months</time_frame>
    <description>Reasons for forgoing subsequent treatment after progression on first-line treatment</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Tumor micro environment</measure>
    <time_frame>54 months</time_frame>
    <description>Percentage of stroma and tumor immune infiltrate in metastatic tumor tissue as predictor of response to treatment and survival.</description>
  </other_outcome>
  <other_outcome>
    <measure>Stromal markers in blood</measure>
    <time_frame>54 months</time_frame>
    <description>Concentration of ADAM12 in blood</description>
  </other_outcome>
  <other_outcome>
    <measure>Growth velocity of patient derived tumor organoids</measure>
    <time_frame>54 months</time_frame>
    <description>Growth velocity of tumor organoids after treatment measured in days</description>
  </other_outcome>
  <other_outcome>
    <measure>ctDNA</measure>
    <time_frame>54 months</time_frame>
    <description>Concentration circulating tumour DNA (ctDNA) as a marker of response to treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>Fecal microbiome</measure>
    <time_frame>54 months</time_frame>
    <description>Composition of the fecal microbiome as a potential biomarker for response to treatment and toxicity</description>
  </other_outcome>
  <other_outcome>
    <measure>Costs associated with treatment of F-Nal-IRI, CapCar and CapOx</measure>
    <time_frame>54 months</time_frame>
    <description>The cost effectiveness in terms of QUALYs associated with treatment of F-Nal-IRI, CapCar and CapOx</description>
  </other_outcome>
  <other_outcome>
    <measure>Stromal Markers in tumor</measure>
    <time_frame>54 months</time_frame>
    <description>Expression of ADAM12 in metastatic tumor tissue</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">310</enrollment>
  <condition>Esophageal Cancer</condition>
  <arm_group>
    <arm_group_label>Liposomal irinotecan, leucovorin and 5FU</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV Nal-IRI 80 mg/m² (expressed as irinotecan hydrochloride (HCl) salt), folinic acid 400 mg/m², fluorouracil 2400 mg/m² over 46 h, every 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Carboplatin and capecitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV and PO Capecitabine 1000 mg/m2 and carboplatin area under the curve (AUC5), every three weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>oxaliplatin and capecitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV and PO Capecitabine 1000 mg/m2 and oxaliplatin 130 mg/m2, every three weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liposomal Irinotecan</intervention_name>
    <description>Iv liposomal irinotecan</description>
    <arm_group_label>Liposomal irinotecan, leucovorin and 5FU</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>IV Carboplatin</description>
    <arm_group_label>Carboplatin and capecitabine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>PO Capecitabine</description>
    <arm_group_label>Carboplatin and capecitabine</arm_group_label>
    <arm_group_label>oxaliplatin and capecitabine</arm_group_label>
    <other_name>Xeloda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>IV Oxaliplatin</description>
    <arm_group_label>oxaliplatin and capecitabine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-fluorouracil</intervention_name>
    <description>IV 5-fluorouracil</description>
    <arm_group_label>Liposomal irinotecan, leucovorin and 5FU</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>IV Leucovorin</description>
    <arm_group_label>Liposomal irinotecan, leucovorin and 5FU</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must provide written informed consent according to International Conference&#xD;
             on Harmonization (ICH)/Guideline for Good Clinical practice (GCP), and national/local&#xD;
             regulations prior to any screening procedures.&#xD;
&#xD;
          -  Male or female adult patients (&gt; 18 years).&#xD;
&#xD;
          -  Patients with histologically confirmed diagnosis of metastatic or irresectable human&#xD;
             epidermal growth (HER2) negative adenocarcinoma of the stomach or oesophagus; patients&#xD;
             with HER2 positive disease are eligible when treatment with trastuzumab is&#xD;
             contraindicated. If histology cannot be obtained, cytology is acceptable to prove&#xD;
             metastatic disease.&#xD;
&#xD;
          -  Patients with metastatic or irresectable adenocarcinoma of the stomach or oesophagus&#xD;
             not pre-treated with chemotherapy or radiotherapy for irresectable or metastatic&#xD;
             disease. Palliative radiotherapy on the primary tumor or a metastatic lesion is&#xD;
             allowed if other untreated lesions eligible for evaluation are present.&#xD;
&#xD;
          -  Measurable disease as assessed by RECIST 1.1&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) (WHO) performance status 0-2&#xD;
&#xD;
          -  Patient has adequate bone marrow and organ function as defined by the following&#xD;
             laboratory values:&#xD;
&#xD;
               -  Absolute Neutrophil Count (ANC) &gt; 1.5 x 109 /L&#xD;
&#xD;
               -  Hemoglobin (Hgb) &gt; 5.6 mmol/L&#xD;
&#xD;
               -  Platelets &gt; 100 x 109 /L&#xD;
&#xD;
          -  Serum total bilirubin within ≤ 1.5 x ULN (upper limit of normal); or total bilirubin &lt;&#xD;
             3.0 x upper limit of normal (ULN) with direct bilirubin within normal range in&#xD;
             patients with well documented Gilbert's syndrome; biliary drainage is allowed for&#xD;
             biliary obstruction&#xD;
&#xD;
          -  Serum creatinine &lt; 1.5 x ULN or creatinine clearance &gt;30 mL/min/1.73 m2&#xD;
&#xD;
          -  Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) &lt; 2.5x ULN within&#xD;
             normal range or &lt; 5.0 x ULN if liver metastases are present&#xD;
&#xD;
          -  If a female patient is of child-bearing potential, as evidenced by regular menstrual&#xD;
             periods, she must have a negative serum pregnancy test, beta-human chorionic&#xD;
             gonadotropin (β-hCG) documented 72 hours prior to the first administration of study&#xD;
             drug. If sexually active, the patient must agree to use contraception considered&#xD;
             adequate and appropriate by the Investigator during the period of administration of&#xD;
             study drug and after the end of treatment as recommended.&#xD;
&#xD;
          -  Absence of any psychological, familial, sociological or geographical condition&#xD;
             potentially hampering compliance with the study protocol and follow-up schedule; those&#xD;
             conditions should be discussed with the patient before registration in the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior systemic treatment for metastatic or irresectable stomach or oesophageal cancer.&#xD;
&#xD;
          -  Evidence of disease progression within six months after completion of adjuvant or&#xD;
             neoadjuvant treatment (whichever is last) containing a fluoropyrimidine and/or&#xD;
             platinum compound and/or irinotecan; progression on neoadjuvant chemoradiation with&#xD;
             carboplatin area under the curve (AUC2) and paclitaxel 50 mg/m2 within this time frame&#xD;
             is allowed.&#xD;
&#xD;
          -  All target lesions in a radiation field without documented disease progression. 11&#xD;
&#xD;
          -  Patient has known brain metastases, unless previously treated and well-controlled for&#xD;
             at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2&#xD;
             scans at least 4 weeks apart).&#xD;
&#xD;
          -  Past or current malignancy other than entry diagnosis interfering with prognosis of&#xD;
             metastatic esophagogastric cancer.&#xD;
&#xD;
          -  Known uncontrollable hypersensitivity or contraindications to any of the components of&#xD;
             liposomal irinotecan (Nal-IRI) other liposomal irinotecan formulations, irinotecan,&#xD;
             fluoropyrimidines, leucovorin, oxaliplatin, carboplatin. Patients with previous dose&#xD;
             reductions or delays are eligible.&#xD;
&#xD;
          -  Complete dihydropyrimidine dehydrogenase deficiency .&#xD;
&#xD;
          -  Patient has active, uncontrolled bacterial, viral or fungal infection(s) requiring&#xD;
             systemic therapy.&#xD;
&#xD;
          -  Patient has known past or active infection with human immunodeficiency virus (HIV),&#xD;
             hepatitis B or hepatitis C.&#xD;
&#xD;
          -  Signs of interstitial lung disease (ILD)&#xD;
&#xD;
          -  Patient has any other concurrent severe and/or uncontrolled medical condition that&#xD;
             would, in the investigator's judgment contraindicate patient participation in the&#xD;
             clinical study.&#xD;
&#xD;
          -  Use of other investigational drugs within 30 days of enrollment.&#xD;
&#xD;
          -  Patient is enrolled in any other clinical protocol or investigational trial that will&#xD;
             interfere with the primary endpoint.&#xD;
&#xD;
          -  Patients who in the investigators' opinion may be unwilling, unable or unlikely to&#xD;
             comply with requirements of the study protocol.&#xD;
&#xD;
          -  Current use or any use in last two weeks of strong cytochrome P4503A (CYP3A-enzyme),&#xD;
             CYP2C8, and/or strong UDP glucuronosyltransferase (UGT1A) inhibitors/inhibitors&#xD;
&#xD;
          -  Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use&#xD;
             a reliable method of birth control, during therapy and for 3 months following the last&#xD;
             dose of study treatment.&#xD;
&#xD;
          -  Treatment within 4 weeks with dihydropyrimidine dehydrogenase (DPD) inhibitors,&#xD;
             including sorivudine or its chemically related analogues such as brivudine.&#xD;
&#xD;
          -  Pre-existing motor or sensory neurotoxicity greater than WHO grade 1.&#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>Jan M Prins, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hanneke WM van Laarhoven, MD, PhD, PhD</last_name>
    <phone>31 20 5665955</phone>
    <email>h.vanlaarhoven@amc.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lyda ter Hofstede-Ruiter</last_name>
    <phone>31 20 5665955</phone>
    <email>l.ruiter@amc.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>VieCuri</name>
      <address>
        <city>Venlo</city>
        <state>Limburg</state>
        <zip>5912 BL</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Y Van der Wouw</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Jeroen Bosch Ziekenhuis</name>
      <address>
        <city>'s-Hertogenbosch</city>
        <zip>5223 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Miriam Wumkes</last_name>
      <phone>31 73 5538225</phone>
      <email>m.wumkes@jbz.nl</email>
    </contact>
    <contact_backup>
      <last_name>Linda van Zutphen</last_name>
      <phone>31 73 553 38 63</phone>
      <email>l.v.zutphen@jbz.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Meander MC</name>
      <address>
        <city>Amersfoort</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Geert Cirkel</last_name>
      <phone>31 033 850 7278</phone>
      <email>M.Broekhuizen@iknl.nl</email>
    </contact>
    <contact_backup>
      <last_name>Els Wink</last_name>
      <phone>033-850 7278</phone>
      <email>Studieteamoncologie@meandermc.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Academic Medical Center, Medical Oncology</name>
      <address>
        <city>Amsterdam</city>
        <zip>1100 DD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>H WM van Laarhoven, MD, PhD, PhD</last_name>
      <phone>31 20 5665955</phone>
      <email>h.vanlaarhoven@amc.uva.nl</email>
    </contact>
    <contact_backup>
      <last_name>Lyda ter Hofstede</last_name>
      <phone>31 20 5668229</phone>
      <email>trialmedonc@amc.uva.nl</email>
    </contact_backup>
    <investigator>
      <last_name>H. WM van Laarhoven, MD, PhD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Rijnstate Ziekenhuis</name>
      <address>
        <city>Arnhem</city>
        <zip>6815 AD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>T van Voorthuizen</last_name>
      <phone>31 06 52484287</phone>
      <email>TvanVoorthuizen@rijnstate.nl</email>
    </contact>
    <contact_backup>
      <last_name>H Verheij</last_name>
      <phone>31 06 52484287</phone>
      <email>HVerheij@Rijnstate.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Amphia Ziekenhuis</name>
      <address>
        <city>Breda</city>
        <zip>4818 CK</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>A ten Tije</last_name>
      <phone>31 76 59555000</phone>
      <email>atentije@amphia.nl</email>
    </contact>
    <contact_backup>
      <last_name>Debbie Arens</last_name>
      <phone>31 76 5955146</phone>
      <email>DArens@amphia.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Reinier de Graaf Gasthuis</name>
      <address>
        <city>Delft</city>
        <zip>2625 AD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>A J Vulink</last_name>
      <phone>31 015 260 34 82</phone>
      <email>a.vulink@rdgg.nl</email>
    </contact>
    <contact_backup>
      <last_name>C. Haazer</last_name>
      <phone>31 015 260 38 60</phone>
      <email>c.haazer@rdgg.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Hagaziekenhuis</name>
      <address>
        <city>Den Haag</city>
        <zip>2545 AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>P Quarles</last_name>
      <phone>31 (0)70 2102143</phone>
      <email>P.Quarles@hagaziekenhuis.nl</email>
    </contact>
    <contact_backup>
      <last_name>Yorik Visser</last_name>
      <phone>31 (0)70 2102143</phone>
      <email>Y.Visser@hagaziekenhuis.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Catherina Ziekenhuis</name>
      <address>
        <city>Eindhoven</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jan Creemers</last_name>
      <phone>31 040 2399111</phone>
      <email>geert-jan.creemers@catharinaziekenhuis.nl</email>
    </contact>
    <contact_backup>
      <last_name>Marjan Laven</last_name>
      <phone>31 040 2399111</phone>
      <email>marjan.laven@catharinaziekenhuis.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Admiraal de Ruijter Ziekenhuis</name>
      <address>
        <city>Goes</city>
        <zip>4460 AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>H K van Halteren</last_name>
      <phone>31 113 234897</phone>
      <email>hkvanhalteren@adzr.nl</email>
    </contact>
    <contact_backup>
      <last_name>C van Netten</last_name>
      <phone>31 113 234897</phone>
      <email>c.vannetten@adzr.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Treant zorggroep</name>
      <address>
        <city>Hoogeveen</city>
        <zip>7909 AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>M Beerepoot</last_name>
      <phone>+31 6 4611 9397</phone>
      <email>m.beerepoot@treant.nl</email>
    </contact>
    <contact_backup>
      <last_name>A Eerens</last_name>
      <phone>+31 6 4611 9397</phone>
      <email>a.eerens@treant.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>VieCurie</name>
      <address>
        <city>Roermond</city>
        <zip>6043 CV</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Y v.d. Wouw</last_name>
      <phone>31 0475-382113</phone>
      <email>yvdwouw@viecuri.nl</email>
    </contact>
    <contact_backup>
      <last_name>W Heuts</last_name>
      <phone>31 0475 382113</phone>
      <email>wheuts@viecuri.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Laurentius Ziekenhuis</name>
      <address>
        <city>Roermond</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>M O den Boer</last_name>
      <phone>31 0475 38 24 66</phone>
      <email>marien.denboer@lzr.nl</email>
    </contact>
    <contact_backup>
      <last_name>Wendy Heuts</last_name>
      <phone>31 0475 38 21 13</phone>
      <email>Wendy.heuts@lzr.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Bravis ziekenhuis locatie Roosendaal</name>
      <address>
        <city>Roosendaal</city>
        <zip>4708 AE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Helga Droogendijk</last_name>
      <phone>31 88 706 6820</phone>
      <email>h.droogendijk@bravis.nl</email>
    </contact>
    <contact_backup>
      <last_name>José Schellekens</last_name>
      <phone>31 88 706 6820</phone>
      <email>j.schellekens@bravis.nl</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>UMCU</name>
      <address>
        <city>Utrecht</city>
        <zip>3508 GA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>N Haj Mohammad</last_name>
      <phone>+31 88 75 56263</phone>
      <email>N.HajMohammad@umcutrecht.nl</email>
    </contact>
    <contact_backup>
      <last_name>E van Liempt</last_name>
      <phone>+31 88 75 56263</phone>
      <email>P.A.G.vanLiempt@umcutrecht.nl</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>October 29, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>December 15, 2022</last_update_submitted>
  <last_update_submitted_qc>December 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</investigator_affiliation>
    <investigator_full_name>H.W.M. van Laarhoven</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>palliative chemotherapy</keyword>
  <keyword>metastatic esophagogastric cancer</keyword>
  <keyword>Efficacy</keyword>
  <keyword>toxicity</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Fluorouracil</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Irinotecan</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/NCT03764553
org study id: 2018_256
nct id: NCT03764553
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a multi-center, open label, randomized phase II trial for patients with previously
      untreated metastatic or locally advanced esophagogastric cancer, using a pick the winner
      design to identify the best combination therapy in terms of progression free survival and
      neurotoxicity.
The sample size to identify the best combination therapy is based on the following decision
      making strategy. With less or even zero neurotoxicity grade 2-4 (defined as worst toxicity),
      the Nal-IRI plus 5FU/LV (Fluorouracil/leucovorin)combination is expected to outperform the
      standard combination capecitabine plus oxaliplatin and may also outperform capecitabine plus
      carboplatin. To compensate for a higher neurotoxicity grade 2-4 level, the capecitabine
      combinations should demonstrate increased progression free survival (PFS) according to the
      next schedule.

      Table 1. Decision making strategy

      Difference in % neurotoxicity grade 2-4 Compensating Increase in PFS >10 - 30% + 3 months >30
      - 50% + 4 months

      The total number to be included will be 269. Patients will be randomized to respectively the
      Nal-IRI plus 5FU, the capecitabine plus carboplatin and capecitabine plus oxaliplatin group
      following a 2:2:1 scheme until 49 patients have been included in the capecitabine plus
      oxaliplatin group and following a 1:1:0 scheme 10 afterwards for the remaining patients.
      Taking into account 15% withdrawal of patients from the trial before start of study
      medication, the investigators will include 310 patients.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: phase 2 study
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival
time frame: 42 months
description: To compare the progression free survival
measure: Number of participants with treatment-related Neurotoxicity
time frame: 42 months
description: Number of participants with treatment-related Neurotoxicity according to CTCAE v4.0
measure: Overall survival
time frame: 54 months
description: To determine the overall survival of F-Nal-IRI, capecitabine/Carboplatin (CapCar) and capecitabine/oxaliplatin (CapOx)
measure: response rate
time frame: 42 months
description: To determine the response rate of F-Nal-IRI, CapCar and CapOx
measure: adverse events
time frame: 42 months
description: To determine the adverse events of F-Nal-IRI, CapCar and CapOx according to NCI common toxicity criteria (CTC) version 4
measure: Quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ C30))
time frame: 42 months
description: Overall Quality of life ranging from 0-100 with 100 being best Quality of Life
measure: percentage subsequent treatment lines
time frame: 42 months
description: The percentage of patients proceeding to subsequent lines of treatment after progression and describe the types of treatment.
measure: the reasons for forgoing subsequent treatment
time frame: 42 months
description: Reasons for forgoing subsequent treatment after progression on first-line treatment
measure: Tumor micro environment
time frame: 54 months
description: Percentage of stroma and tumor immune infiltrate in metastatic tumor tissue as predictor of response to treatment and survival.
measure: Stromal markers in blood
time frame: 54 months
description: Concentration of ADAM12 in blood
measure: Growth velocity of patient derived tumor organoids
time frame: 54 months
description: Growth velocity of tumor organoids after treatment measured in days
measure: ctDNA
time frame: 54 months
description: Concentration circulating tumour DNA (ctDNA) as a marker of response to treatment
measure: Fecal microbiome
time frame: 54 months
description: Composition of the fecal microbiome as a potential biomarker for response to treatment and toxicity
measure: Costs associated with treatment of F-Nal-IRI, CapCar and CapOx
time frame: 54 months
description: The cost effectiveness in terms of QUALYs associated with treatment of F-Nal-IRI, CapCar and CapOx
measure: Stromal Markers in tumor
time frame: 54 months
description: Expression of ADAM12 in metastatic tumor tissue
arm group label: Liposomal irinotecan, leucovorin and 5FU
arm group type: Experimental
description: IV Nal-IRI 80 mg/m² (expressed as irinotecan hydrochloride (HCl) salt), folinic acid 400 mg/m², fluorouracil 2400 mg/m² over 46 h, every 2 weeks.
arm group label: Carboplatin and capecitabine
arm group type: Experimental
description: IV and PO Capecitabine 1000 mg/m2 and carboplatin area under the curve (AUC5), every three weeks.
arm group label: oxaliplatin and capecitabine
arm group type: Experimental
description: IV and PO Capecitabine 1000 mg/m2 and oxaliplatin 130 mg/m2, every three weeks.
intervention type: Drug
intervention name: Liposomal Irinotecan
description: Iv liposomal irinotecan
arm group label: Liposomal irinotecan, leucovorin and 5FU
intervention type: Drug
intervention name: Carboplatin
description: IV Carboplatin
arm group label: Carboplatin and capecitabine
intervention type: Drug
intervention name: Capecitabine
description: PO Capecitabine
arm group label: Carboplatin and capecitabine
arm group label: oxaliplatin and capecitabine
other name: Xeloda
intervention type: Drug
intervention name: Oxaliplatin
description: IV Oxaliplatin
arm group label: oxaliplatin and capecitabine
intervention type: Drug
intervention name: 5-fluorouracil
description: IV 5-fluorouracil
arm group label: Liposomal irinotecan, leucovorin and 5FU
intervention type: Drug
intervention name: Leucovorin
description: IV Leucovorin
arm group label: Liposomal irinotecan, leucovorin and 5FU
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jan M Prins, MD, PhD
role: Study Director
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
last name: Hanneke WM van Laarhoven, MD, PhD, PhD
phone: 31 20 5665955
email: h.vanlaarhoven@amc.nl
last name: Lyda ter Hofstede-Ruiter
phone: 31 20 5665955
email: l.ruiter@amc.nl
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
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investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
investigator full name: H.W.M. van Laarhoven
investigator title: Principal Investigator
mesh term: Leucovorin
mesh term: Carboplatin
mesh term: Fluorouracil
mesh term: Capecitabine
mesh term: Oxaliplatin
mesh term: Irinotecan
sharing ipd: No