<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/NCT03762564</url>
  </required_header>
  <id_info>
    <org_study_id>RAMOS</org_study_id>
    <secondary_id>AIO-STO-0216</secondary_id>
    <secondary_id>2016-003850-33</secondary_id>
    <nct_id>NCT03762564</nct_id>
  </id_info>
  <brief_title>Study With Paclitaxel +/- Ramucirumab in Patients With Squamous-cell Carcinoma of the Esophagus After Prior Therapy</brief_title>
  <acronym>RAMOS</acronym>
  <official_title>A Randomized, Multicenter Open Label Phase II Trial of Paclitaxel + Ramucirumab Versus Paclitaxel Alone in Patients With Squamous-cell Carcinoma of the Esophagus, Refractory or Intolerant to Combination Therapy With Fluoropyrimidine and Platinum-based Drugs - The RAMOS STUDY</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Trium Analysis Online GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, randomized, controlled, open-label phase II study including patients&#xD;
      with squamous-cell carcinoma of the esophagus, refractory or intolerant to combination&#xD;
      therapy with Fluoropyrimidine and Platinum-based drugs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase II, randomized, open-label multi-center study comparing treatment of&#xD;
      paclitaxel plus ramucirumab with paclitaxel monotherapy in patients with advanced&#xD;
      squamous-cell carcinoma (SCC) of the esophagus.&#xD;
&#xD;
      Adult patients with histologically or cytologically confirmed advanced squamous-cell&#xD;
      carcinoma of the esophagus and refractory or intolerant to combination therapy with&#xD;
      Fluoropyrimidine and Platinum-based drugs will be enrolled in the study.&#xD;
&#xD;
      A total number of 186 patients will be enrolled (Randomization 1:1). 93 patients will be&#xD;
      treated with paclitaxel + ramucirumab (Arm A) and 93 with paclitaxel (Arm B).&#xD;
&#xD;
      Randomization will be stratified by time of progression during or after end of first-line&#xD;
      therapy (≤3 months vs. &gt;3 months).&#xD;
&#xD;
      The primary objective is to compare overall survival (OS) after 6 months in patients with&#xD;
      squamous-cell carcinoma of the esophagus, refractory or intolerant to combination therapy&#xD;
      with Fluoropyrimidine and Platinum-based drugs receiving paclitaxel with ramucirumab versus&#xD;
      paclitaxel alone in the intent-to-treat population (ITT). OS is defined as the time from&#xD;
      randomization to death from any cause.&#xD;
&#xD;
      Patients in Arm A (investigational arm) receive Paclitaxel 80 mg/m2 on day 1, 8, 15 plus&#xD;
      Ramucirumab 8 mg/kg i.v. infusion on day 1 and 15 every 4 weeks. Patients in Arm B (control&#xD;
      arm) receive Paclitaxel 80 mg/m2 on day 1, 8, 15 every 4 weeks. Study treatment will be&#xD;
      continued until progression or intolerable toxicity, but for a maximum of 1 year.&#xD;
&#xD;
      Tumor assessment will be performed according to clinical routine at screening / baseline and&#xD;
      every 8 weeks.&#xD;
&#xD;
      After discontinuation of study medication, patients will be followed for up to 1 year. Tumor&#xD;
      assessments per CT or MRI will be performed every 2 months for 6 months or until&#xD;
      documentation of disease progression. Follow-up for survival will be done and documented&#xD;
      every 2 months for the 1 year follow-up period after end of treatment.&#xD;
&#xD;
      During treatment, clinical visits (blood cell counts, detection of toxicity) will be&#xD;
      performed prior to every treatment dose. Safety of paclitaxel +/- ramucirumab will be&#xD;
      monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse&#xD;
      events (SAEs) reported. Prior to the start of each cycle and at the 30-day safety follow-up&#xD;
      visit Quality of life (QoL) will be assessed using the European Organization for Research and&#xD;
      treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 8, 2019</start_date>
  <completion_date type="Actual">November 25, 2022</completion_date>
  <primary_completion_date type="Actual">July 4, 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival (OS) at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>OS rate at 6 months, defined as patients who are alive after at 6 months</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>PFS, defined as the time from randomization to the first occurrence of progression, as determined by the investigator using CT criteria, or death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Overall survival according to Kaplan-Meier</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Objective response rate defined as the proportion of patients with complete or partial remission according to RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor control rate</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Tumor control rate defined as the proportion of patients with complete or partial remission or stable disease according to RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (QoL)</measure>
    <time_frame>Up to 1 year and 30 days</time_frame>
    <description>Quality of life (QoL) as measured by EORTC-QLQ-C30 at d1 of each cycle, on EOT (end of treatment) and 30 days after EOT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of adverse events</measure>
    <time_frame>Up to 1 year and 30 days</time_frame>
    <description>incidence and severity of adverse events according to CTCAE (Common Terminology Criteria for Adverse Events) Version 4 criteria as assessed at day 1, 8 and 15 of every cycle during treatment for a maximum of 12 months and until 30 days after the last dose of study drug</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Squamous Cell Carcinoma of the Esophagus</condition>
  <arm_group>
    <arm_group_label>Arm A (Paclitaxel + Ramucirumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Paclitaxel 80 mg/m2 as 1 hour intravenous infusion on day 1, 8, 15 plus Ramucirumab 8 mg/kg as 1 hour intravenous infusion on day 1 and 15 qd 28</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (control arm)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Paclitaxel 80 mg/m2 as 1 hour intravenous infusion on day 1, 8, 15 qd 28</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ramucirumab</intervention_name>
    <description>Ramucirumab 8 mg/kg i.v. infusion on day 1 and 15</description>
    <arm_group_label>Arm A (Paclitaxel + Ramucirumab)</arm_group_label>
    <other_name>Cyramza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Paclitaxel 80 mg/m2 on day 1, 8, 15</description>
    <arm_group_label>Arm A (Paclitaxel + Ramucirumab)</arm_group_label>
    <arm_group_label>Arm B (control arm)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed written informed consent;&#xD;
&#xD;
          2. Male or female* ≥ 18 years of age; Patients in reproductive age must be willing to use&#xD;
             adequate contraception during the study and for 6 months after the end of ramucirumab&#xD;
             treatment (Appropriate contraception is defined as surgical sterilization (e.g.,&#xD;
             bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch,&#xD;
             oral), and double-barrier methods (any double combination of: IUD, male or female&#xD;
             condom with spermicidal gel, diaphragm, sponge, cervical cap)). Female patients with&#xD;
             childbearing potential need to have a negative pregnancy test within 7 days before&#xD;
             study start.&#xD;
&#xD;
             *There are no data that indicate special gender distribution. Therefore, patients will&#xD;
             be enrolled in the study gender-independently.&#xD;
&#xD;
          3. Histologically proven squamous cell carcinoma of the esophagus&#xD;
&#xD;
               -  Adult patients with metastatic or locally advanced squamous-cell carcinoma of the&#xD;
                  esophagus, not amenable to potentially curative resection, who are refractory to&#xD;
                  or intolerant of prior platinum/fluoropyrimidine combination therapy. The&#xD;
                  definition of refractory should be defined as follows:&#xD;
&#xD;
               -  Patients whose PD or recurrence was confirmed by imaging during their initial&#xD;
                  chemotherapy (including chemoradiation) or within 8 weeks after the last dose of&#xD;
                  chemotherapy will be assessed as &quot;refractory&quot;.&#xD;
&#xD;
               -  Patients after radical resection in conjunction with chemotherapy, including&#xD;
                  neoadjuvant/adjuvant therapy and chemoradiation, whose recurrence was confirmed&#xD;
                  by imaging within 24 weeks after the last dose of chemotherapy, will be&#xD;
                  determined &quot;refractory&quot;.&#xD;
&#xD;
          4. Measurable or non-measurable but evaluable disease determined using guidelines in&#xD;
             RECIST 1.1 as confirmed within 28 days before randomization&#xD;
&#xD;
          5. ECOG performance status 0-1;&#xD;
&#xD;
          6. Life expectancy &gt; 12 weeks;&#xD;
&#xD;
          7. Adequate hematological, hepatic and renal functions:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;&#xD;
&#xD;
               -  Platelets ≥ 100 x 109/L;&#xD;
&#xD;
               -  Hemoglobin ≥9 g/dL (5.58 mmol/L&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 times the upper normal limit (UNL)&#xD;
&#xD;
               -  AST (SGOT) and ALT (SGPT) ≤ 2.5 x UNL in absence of liver metastases, or ≤ 5 x&#xD;
                  UNL in presence of liver metastases; AP ≤ 5 x UNL&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x upper limit of normal, or creatinine clearance (measured&#xD;
                  via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is &gt;1.5&#xD;
                  times the ULN, a 24-hour urine collection to calculate creatinine clearance must&#xD;
                  be performed)&#xD;
&#xD;
               -  Urinary protein ≤1+ on dipstick or routine urinalysis (UA; if urine dipstick or&#xD;
                  routine analysis is ≥2+, a 24-hour urine collection for protein must demonstrate&#xD;
                  &lt;1000 mg of protein in 24 hours to allow participation in this protocol).&#xD;
&#xD;
               -  Adequate coagulation function as defined by International Normalized Ratio (INR)&#xD;
                  ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless&#xD;
                  receiving anticoagulation therapy). Patients on full-dose anticoagulation must be&#xD;
                  on a stable dose (minimum duration 14 days) of oral anticoagulant or low&#xD;
                  molecular weight heparin (LMWH). Patients receiving warfarin/ phenprocoumon must&#xD;
                  be switched to low molecular weight heparin and have an INR ≤3.0 prior to first&#xD;
                  dose of protocol therapy. For heparin and LMWH there should be no active bleeding&#xD;
                  (that is, no bleeding within 14 days prior to first dose of protocol therapy) or&#xD;
                  pathological condition present that carries a high risk of bleeding (for example,&#xD;
                  tumor involving major vessels or known varices).&#xD;
&#xD;
          8. Ability to comply with scheduled assessments and with management of toxicities&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Other tumor type than squamous carcinoma (e.g. leiomyosarcoma, lymphoma) or a second&#xD;
             cancer except in patients with squamous or basal cell carcinoma of the skin or&#xD;
             carcinoma in situ of the cervix that has been effectively treated. Patients curatively&#xD;
             treated and disease-free for at least 5 years will be discussed with the sponsor&#xD;
             before inclusion.&#xD;
&#xD;
          2. Patients with significant malnutrition who receive intravenous hyperalimentation or&#xD;
             require continuous infusion therapy with hospitalization.&#xD;
&#xD;
          3. Patients with apparent tumor invasion on organs located adjacent to the esophageal&#xD;
             disease. Patients will be excluded if they are receiving stent therapy in esophagus or&#xD;
             respiratory tract.&#xD;
&#xD;
          4. Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not&#xD;
             indicated in the study protocol.&#xD;
&#xD;
          5. Previous therapy with paclitaxeI&#xD;
&#xD;
          6. Current treatment with any anti-cancer therapy ≤ 2 weeks prior to study treatment&#xD;
             start, unless rapidly progressing disease is measured&#xD;
&#xD;
          7. Concurrent treatment with any other anti-cancer therapy&#xD;
&#xD;
          8. Previous exposure to a VEGF or VEGFR inhibitor or any antiangiogenic agent, or prior&#xD;
             enrolment in this study&#xD;
&#xD;
          9. Patient has undergone major surgery within 28 days prior to first dose of protocol&#xD;
             therapy, or minor surgery/subcutaneous venous access device placement within 7 days&#xD;
             prior to first dose of protocol therapy. The patient has elective or planned major&#xD;
             surgery to be performed during the course of the clinical trial.&#xD;
&#xD;
         10. Grade 3-4 GI bleeding within 3 months prior to enrollment&#xD;
&#xD;
         11. History of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other&#xD;
             significant thromboembolism (venous port or catheter thrombosis or superficial venous&#xD;
             thrombosis are not considered &quot;significant&quot;) during the 3 months prior to first dose&#xD;
             of protocol therapy-&#xD;
&#xD;
         12. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a&#xD;
             history of hepatic encephalopathy or clinically meaningful ascites resulting from&#xD;
             cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis&#xD;
             requiring diuretics or paracentesis.&#xD;
&#xD;
         13. Known brain or leptomeningeal metastases.&#xD;
&#xD;
         14. Known allergic/ hypersensitivity reaction to any of the components of the treatment.&#xD;
&#xD;
         15. Other serious illness or medical conditions within the last 12 months prior to study&#xD;
             drug administration.&#xD;
&#xD;
         16. Any arterial thromboembolic events, including but not limited to myocardial&#xD;
             infarction, transient ischemic attack, cerebrovascular accident, or unstable angina,&#xD;
             within 6 months prior to first dose of protocol.&#xD;
&#xD;
         17. The patient has uncontrolled or poorly-controlled hypertension (&gt;160 mmHg systolic or&#xD;
             &gt; 100 mmHg diastolic for &gt;4 weeks) despite standard medical management.&#xD;
&#xD;
         18. Active uncontrolled infection.&#xD;
&#xD;
         19. Active disseminated intravascular coagulation.&#xD;
&#xD;
         20. Any other serious concomitant disease or medical condition that in the judgment of the&#xD;
             investigator renders the subject at high risk of treatment complication or reduced the&#xD;
             probability of assessing clinical effect&#xD;
&#xD;
         21. Prior history of GI perforation/fistula (within 6 months of first dose of protocol&#xD;
             therapy) or risk factors for perforation.&#xD;
&#xD;
         22. Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first&#xD;
             dose of protocol therapy.&#xD;
&#xD;
         23. The patient is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal&#xD;
             anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others),&#xD;
             dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose&#xD;
             325 mg/day) is permitted.&#xD;
&#xD;
         24. Concurrent treatment with other experimental drugs or participation in another&#xD;
             clinical trial with any investigational drug within 30 days prior to treatment start.&#xD;
&#xD;
         25. Known drug abuse/ alcohol abuse.&#xD;
&#xD;
         26. Lack of resolution of all toxic effects (excluding alopecia) of prior chemotherapy,&#xD;
             prior radiotherapy or surgical procedure to National Cancer Institute (NCI) Common&#xD;
             Terminology Criteria for Adverse Events (CTCAE) grade &lt; 1. Note: Neuropathy due to&#xD;
             prior chemotherapy is allowed if not &gt; NCI Grade II according to CTCAE version 4.0.&#xD;
&#xD;
         27. Subject pregnant or breast feeding, or planning to become pregnant within 6 months&#xD;
             after the end of treatment.&#xD;
&#xD;
         28. Subject (male or female) is not willing to use highly effective methods of&#xD;
             contraception (per institutional standard) during treatment and for 6 months (male or&#xD;
             female) after the end of treatment.&#xD;
&#xD;
         29. Patients with a psychiatric illness or patients imprisoned or working in the&#xD;
             institution of the treating physician.&#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>Salah-Eddin Al-Batran, Prof. Dr.</last_name>
    <role>Study Chair</role>
    <affiliation>Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institute for Clinical Cancer Research Krankenhaus Nordwest</name>
      <address>
        <city>Frankfurt</city>
        <zip>60488</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Technische Universität München Klinikum rechts der Isar</name>
      <address>
        <city>Muenchen</city>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 30, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 3, 2018</study_first_posted>
  <last_update_submitted>December 7, 2022</last_update_submitted>
  <last_update_submitted_qc>December 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Squamous Cell Carcinoma of the Esophagus</keyword>
  <keyword>Ramucirumab</keyword>
  <keyword>Paclitaxel</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
    <mesh_term>Esophageal Squamous Cell Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Ramucirumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No IPD will be shared</ipd_description>
  </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/NCT03762564
org study id: RAMOS
secondary id: AIO-STO-0216
secondary id: 2016-003850-33
nct id: NCT03762564
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This is a multicenter, randomized, controlled, open-label phase II study including patients
      with squamous-cell carcinoma of the esophagus, refractory or intolerant to combination
      therapy with Fluoropyrimidine and Platinum-based drugs.
This is a phase II, randomized, open-label multi-center study comparing treatment of
      paclitaxel plus ramucirumab with paclitaxel monotherapy in patients with advanced
      squamous-cell carcinoma (SCC) of the esophagus.

      Adult patients with histologically or cytologically confirmed advanced squamous-cell
      carcinoma of the esophagus and refractory or intolerant to combination therapy with
      Fluoropyrimidine and Platinum-based drugs will be enrolled in the study.

      A total number of 186 patients will be enrolled (Randomization 1:1). 93 patients will be
      treated with paclitaxel + ramucirumab (Arm A) and 93 with paclitaxel (Arm B).

      Randomization will be stratified by time of progression during or after end of first-line
      therapy (≤3 months vs. >3 months).

      The primary objective is to compare overall survival (OS) after 6 months in patients with
      squamous-cell carcinoma of the esophagus, refractory or intolerant to combination therapy
      with Fluoropyrimidine and Platinum-based drugs receiving paclitaxel with ramucirumab versus
      paclitaxel alone in the intent-to-treat population (ITT). OS is defined as the time from
      randomization to death from any cause.

      Patients in Arm A (investigational arm) receive Paclitaxel 80 mg/m2 on day 1, 8, 15 plus
      Ramucirumab 8 mg/kg i.v. infusion on day 1 and 15 every 4 weeks. Patients in Arm B (control
      arm) receive Paclitaxel 80 mg/m2 on day 1, 8, 15 every 4 weeks. Study treatment will be
      continued until progression or intolerable toxicity, but for a maximum of 1 year.

      Tumor assessment will be performed according to clinical routine at screening / baseline and
      every 8 weeks.

      After discontinuation of study medication, patients will be followed for up to 1 year. Tumor
      assessments per CT or MRI will be performed every 2 months for 6 months or until
      documentation of disease progression. Follow-up for survival will be done and documented
      every 2 months for the 1 year follow-up period after end of treatment.

      During treatment, clinical visits (blood cell counts, detection of toxicity) will be
      performed prior to every treatment dose. Safety of paclitaxel +/- ramucirumab will be
      monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse
      events (SAEs) reported. Prior to the start of each cycle and at the 30-day safety follow-up
      visit Quality of life (QoL) will be assessed using the European Organization for Research and
      treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival (OS) at 6 months
time frame: 6 months
description: OS rate at 6 months, defined as patients who are alive after at 6 months
measure: Progression-free survival (PFS)
time frame: Up to 2 years
description: PFS, defined as the time from randomization to the first occurrence of progression, as determined by the investigator using CT criteria, or death from any cause
measure: Overall survival
time frame: Up to 2 years
description: Overall survival according to Kaplan-Meier
measure: Objective response rate
time frame: Up to 2 years
description: Objective response rate defined as the proportion of patients with complete or partial remission according to RECIST 1.1
measure: Tumor control rate
time frame: Up to 2 years
description: Tumor control rate defined as the proportion of patients with complete or partial remission or stable disease according to RECIST 1.1
measure: Quality of life (QoL)
time frame: Up to 1 year and 30 days
description: Quality of life (QoL) as measured by EORTC-QLQ-C30 at d1 of each cycle, on EOT (end of treatment) and 30 days after EOT.
measure: Incidence and severity of adverse events
time frame: Up to 1 year and 30 days
description: incidence and severity of adverse events according to CTCAE (Common Terminology Criteria for Adverse Events) Version 4 criteria as assessed at day 1, 8 and 15 of every cycle during treatment for a maximum of 12 months and until 30 days after the last dose of study drug
arm group label: Arm A (Paclitaxel + Ramucirumab)
arm group type: Experimental
description: Paclitaxel 80 mg/m2 as 1 hour intravenous infusion on day 1, 8, 15 plus Ramucirumab 8 mg/kg as 1 hour intravenous infusion on day 1 and 15 qd 28
arm group label: Arm B (control arm)
arm group type: Active Comparator
description: Paclitaxel 80 mg/m2 as 1 hour intravenous infusion on day 1, 8, 15 qd 28
intervention type: Drug
intervention name: Ramucirumab
description: Ramucirumab 8 mg/kg i.v. infusion on day 1 and 15
arm group label: Arm A (Paclitaxel + Ramucirumab)
other name: Cyramza
intervention type: Drug
intervention name: Paclitaxel
description: Paclitaxel 80 mg/m2 on day 1, 8, 15
arm group label: Arm A (Paclitaxel + Ramucirumab)
arm group label: Arm B (control arm)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Salah-Eddin Al-Batran, Prof. Dr.
role: Study Chair
affiliation: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
facility: 
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Neoplasms
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Paclitaxel
mesh term: Ramucirumab
sharing ipd: No
ipd description: No IPD will be shared