<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/NCT02227940</url>
  </required_header>
  <id_info>
    <org_study_id>I 248813</org_study_id>
    <secondary_id>NCI-2014-01766</secondary_id>
    <secondary_id>I 248813</secondary_id>
    <nct_id>NCT02227940</nct_id>
  </id_info>
  <brief_title>Ceritinib and Combination Chemotherapy in Treating Patients With Advanced Solid Tumors or Locally Advanced or Metastatic Pancreatic Cancer</brief_title>
  <official_title>A Phase I Study of Ceritinib (LDK378), a Novel ALK Inhibitor, in Combination With Gemcitabine-Based Chemotherapy in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Roswell Park Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Roswell Park Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of ceritinib and combination&#xD;
      chemotherapy in treating patients with solid tumors that have spread to other places in the&#xD;
      body and usually cannot be cured or controlled with treatment (advanced) or pancreatic cancer&#xD;
      that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or&#xD;
      has spread to other places in the body (metastatic). Ceritinib may stop the growth of tumor&#xD;
      cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy,&#xD;
      such as gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation,&#xD;
      and cisplatin, work in different ways to stop the growth of tumor cells, either by killing&#xD;
      the cells, by stopping them from dividing, or by stopping them from spreading. Giving&#xD;
      ceritinib and more than one drug (combination chemotherapy) may be a better treatment for&#xD;
      solid tumors or pancreatic cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of&#xD;
      ceritinib in combination with gemcitabine (gemcitabine hydrochloride) alone,&#xD;
      gemcitabine/nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) and&#xD;
      gemcitabine/cisplatin in patients with advanced solid malignancies.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Characterize the safety profile of ceritinib in combination with gemcitabine based&#xD;
      chemotherapy in advanced solid malignancies.&#xD;
&#xD;
      II. Determine the pharmacokinetic profile of ceritinib, gemcitabine, nab-paclitaxel,&#xD;
      cisplatin and their metabolites when administered in combination in patients with advanced&#xD;
      solid tumors.&#xD;
&#xD;
      III. Determine the preliminary efficacy of the study combinations.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. Explore potential biomarkers of efficacy to the study combination.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of ceritinib. Patients are assigned to 1 of 3&#xD;
      treatment arms.&#xD;
&#xD;
      ARM 1 (ceritinib MTD then with gemcitabine alone):&#xD;
&#xD;
      Dose Escalation Cohort 1: Patients with advanced solid tumors for whom gemcitabine&#xD;
      hydrochloride-based therapy is clinically appropriate receive ceritinib orally (PO) once&#xD;
      daily (QD) on days 1-28 and gemcitabine hydrochloride intravenously (IV) over 30 minutes on&#xD;
      days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      Expansion Cohort 1E: Once the MTD of ceritinib has been determined, an additional 10 patients&#xD;
      with anaplastic lymphoma kinase positive (ALK-positive) advanced solid tumors who previously&#xD;
      progressed on gemcitabine hydrochloride-based therapy receive ceritinib and gemcitabine&#xD;
      hydrochloride as in the dose escalation cohort 1. Courses repeat every 28 days in the absence&#xD;
      of disease progression or unacceptable toxicity.&#xD;
&#xD;
      ARM 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel):&#xD;
&#xD;
      Dose Escalation Cohort 2: Patients with advanced pancreatic cancer receive ceritinib PO QD on&#xD;
      days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and paclitaxel&#xD;
      albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses&#xD;
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      Expansion Cohort 2E: Once the MTD of ceritinib has been determined, patients with&#xD;
      ALK-positive advanced solid tumors receive ceritinib, gemcitabine hydrochloride, and&#xD;
      paclitaxel albumin-stabilized nanoparticle formulation as in the dose escalation cohort 2.&#xD;
      Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      ARM 3 (ceritinib MTD then with gemcitabine and cisplatin):&#xD;
&#xD;
      Dose Escalation Cohort 3: Patients with advanced solid tumors for whom gemcitabine&#xD;
      hydrochloride and cisplatin-based therapy is clinically appropriate receive ceritinib PO QD&#xD;
      on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and cisplatin IV&#xD;
      on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      Expansion Cohort 3E: Once the MTD of ceritinib has been determined, an additional 10 patients&#xD;
      with ALK-positive advanced solid tumors receive ceritinib, gemcitabine hydrochloride, and&#xD;
      cisplatin as in the dose escalation cohort 3. Courses repeat every 21 days in the absence of&#xD;
      disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for at least 4 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 8, 2015</start_date>
  <completion_date type="Actual">February 12, 2019</completion_date>
  <primary_completion_date type="Actual">December 27, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>MTD and RP2D of ceritinib in combination with gemcitabine hydrochloride alone, defined as the highest dose level at which &lt; 2 of 6 patients experience treatment-related dose limiting toxicity (DLT) (Arms 1 and 1E)</measure>
    <time_frame>Up to day 28</time_frame>
    <description>Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0. The frequency of toxicities will be tabulated for the dose estimated to be the MTD.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MTD and RP2D of ceritinib in combination with gemcitabine hydrochloride and cisplatin, defined as the highest dose level at which &lt; 2 of 6 patients experience treatment-related DLT (Arms 3 and 3E)</measure>
    <time_frame>Up to day 28</time_frame>
    <description>Graded according to NCI CTCAE v4.0. The frequency of toxicities will be tabulated for the dose estimated to be the MTD.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MTD and RP2D of ceritinib in combination with gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation, defined as the highest dose level at which &lt; 2 of 6 patients experience treatment-related DLT (Arms 2 and 2E)</measure>
    <time_frame>Up to day 28</time_frame>
    <description>Graded according to NCI CTCAE v4.0. The frequency of toxicities will be tabulated for the dose estimated to be the MTD.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events of ceritinib in combination with gemcitabine hydrochloride based chemotherapy in advanced solid malignancies according to NCI CTCAE v4.0</measure>
    <time_frame>Up to 4 weeks after end of treatment</time_frame>
    <description>Overall safety profile characterized by type, frequency, severity, timing, seriousness and relationship to study treatment. The frequency of toxicities will be tabulated by grade across all dose levels and cycles.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters of ceritinib and gemcitabine hydrochloride when administered in combination in patients with advanced solid tumors (Arms 1 and 1E)</measure>
    <time_frame>Pre-dose, 0.5, 1-2, 4-5, 6-8, and 24 hours (day 1 of courses 1-2), pre-dose on day 15 of course 1 (ceritinib); prior to end of infusion, 0.5, 1-2, and 4-6 hours post-end of infusion (day 1 of courses 1-2) (gemcitabine hydrochloride)</time_frame>
    <description>A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under the curve (AUC) or clearance (CL) of ceritinib in combination with gemcitabine hydrochloride. The effects of the cytotoxics on ceritinib pharmacokinetic will be evaluated by the model, along with other patient factors that may explain the interpatient variability in pharmacokinetics, including AUC and observed maximum concentration (Cmax).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters of ceritinib, gemcitabine hydrochloride, and paclitaxel albumin-stabilized nanoparticle formulation when administered in combination in patients with advanced solid tumors (Arms 2 and 2E)</measure>
    <time_frame>Pre-dose, 0.5, 1-2, 4-5, 6-8, and 24 hours (day 1 of courses 1-2), pre-dose on day 15 of course 1 (ceritinib); prior to end of infusion, 0.5, 1-2, and 4-6 hours post-end of infusion (day 1 of courses 1-2) (gemcitabine hydrochloride and nab-paclitaxel)</time_frame>
    <description>A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual AUCs or CL of ceritinib in combination with gemcitabine hydrochloride and nab-paclitaxel. The effects of the cytotoxics on ceritinib pharmacokinetic will be evaluated by the model, along with other patient factors that may explain the interpatient variability in pharmacokinetics, including AUC and observed Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters of paclitaxel albumin-stabilized nanoparticle formulation, and cisplatin when administered in combination in patients with advanced solid tumors (Arms 3 and 3E)</measure>
    <time_frame>Pre-dose, 0.5, 1-2, 4-5, 6-8, and 24 hours (day 1 of courses 1-2), pre-dose on day 15 of course 1 (ceritinib); prior to end of infusion, 0.5, 1-2, and 4-6 hours post-end of infusion (day 1 of courses 1-2) (gemcitabine hydrochloride and cisplatin)</time_frame>
    <description>A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual AUCs or CL of ceritinib in combination with gemcitabine hydrochloride and cisplatin. The effects of the cytotoxics on ceritinib pharmacokinetic will be evaluated by the model, along with other patient factors that may explain the interpatient variability in pharmacokinetics, including AUC and observed Cmax.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Up to 4 weeks after end of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate as assessed by the RECIST 1.1</measure>
    <time_frame>Up to 4 weeks after end of treatment</time_frame>
    <description>Objective tumor response will be tabulated overall (and by dose level if appropriate).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Levels of serum and tumor biomarkers</measure>
    <time_frame>Up to 4 weeks after end of treatment</time_frame>
    <description>The relationship between ALK positivity and antitumor effects will be analyzed descriptively and simple statistics if need to.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">38</enrollment>
  <condition>Advanced Malignant Solid Neoplasm</condition>
  <condition>ALK Positive</condition>
  <condition>Metastatic Pancreatic Adenocarcinoma</condition>
  <condition>Stage III Pancreatic Cancer</condition>
  <condition>Stage IV Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Arm 1 (ceritinib MTD then with gemcitabine alone)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Escalation Cohort 1: Patients with advanced solid tumors for whom gemcitabine hydrochloride-based therapy is clinically appropriate receive ceritinib PO (QD on days 1-28 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Expansion Cohort 1E: Once the MTD of ceritinib has been determined, an additional 10 patients with ALK-positive advanced solid tumors who previously progressed on gemcitabine hydrochloride-based therapy receive ceritinib and gemcitabine hydrochloride as in the dose escalation cohort 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Escalation Cohort 2: Patients with advanced pancreatic cancer receive ceritinib PO QD on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Expansion Cohort 2E: Once the MTD of ceritinib has been determined, patients with ALK-positive advanced solid tumors receive ceritinib, gemcitabine hydrochloride, and paclitaxel albumin-stabilized nanoparticle formulation as in the dose escalation cohort 2. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose Escalation Cohort 3: Patients with advanced solid tumors for whom gemcitabine hydrochloride and cisplatin-based therapy is clinically appropriate receive ceritinib PO QD on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and cisplatin IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.&#xD;
Expansion Cohort 3E: Once the MTD of ceritinib has been determined, an additional 10 patients with ALK-positive advanced solid tumors receive ceritinib, gemcitabine hydrochloride, and cisplatin as in the dose escalation cohort 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ceritinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm 1 (ceritinib MTD then with gemcitabine alone)</arm_group_label>
    <arm_group_label>Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)</arm_group_label>
    <arm_group_label>Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)</arm_group_label>
    <other_name>LDK 378</other_name>
    <other_name>LDK378</other_name>
    <other_name>Zykadia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)</arm_group_label>
    <other_name>Abiplatin</other_name>
    <other_name>Blastolem</other_name>
    <other_name>Briplatin</other_name>
    <other_name>CDDP</other_name>
    <other_name>Cis-diammine-dichloroplatinum</other_name>
    <other_name>Cis-diamminedichloridoplatinum</other_name>
    <other_name>Cis-diamminedichloro Platinum (II)</other_name>
    <other_name>Cis-diamminedichloroplatinum</other_name>
    <other_name>Cis-dichloroammine Platinum (II)</other_name>
    <other_name>Cis-platinous Diamine Dichloride</other_name>
    <other_name>Cis-platinum</other_name>
    <other_name>Cis-platinum II</other_name>
    <other_name>Cis-platinum II Diamine Dichloride</other_name>
    <other_name>Cismaplat</other_name>
    <other_name>Cisplatina</other_name>
    <other_name>Cisplatinum</other_name>
    <other_name>Cisplatyl</other_name>
    <other_name>Citoplatino</other_name>
    <other_name>Citosin</other_name>
    <other_name>Cysplatyna</other_name>
    <other_name>DDP</other_name>
    <other_name>Lederplatin</other_name>
    <other_name>Metaplatin</other_name>
    <other_name>Neoplatin</other_name>
    <other_name>Peyrone's Chloride</other_name>
    <other_name>Peyrone's Salt</other_name>
    <other_name>Placis</other_name>
    <other_name>Plastistil</other_name>
    <other_name>Platamine</other_name>
    <other_name>Platiblastin</other_name>
    <other_name>Platiblastin-S</other_name>
    <other_name>Platinex</other_name>
    <other_name>Platinol</other_name>
    <other_name>Platinol- AQ</other_name>
    <other_name>Platinol-AQ</other_name>
    <other_name>Platinol-AQ VHA Plus</other_name>
    <other_name>Platinoxan</other_name>
    <other_name>Platinum</other_name>
    <other_name>Platinum Diamminodichloride</other_name>
    <other_name>Platiran</other_name>
    <other_name>Platistin</other_name>
    <other_name>Platosin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine Hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm 1 (ceritinib MTD then with gemcitabine alone)</arm_group_label>
    <arm_group_label>Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)</arm_group_label>
    <arm_group_label>Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)</arm_group_label>
    <other_name>dFdCyd</other_name>
    <other_name>Difluorodeoxycytidine Hydrochloride</other_name>
    <other_name>Gemzar</other_name>
    <other_name>LY-188011</other_name>
    <other_name>LY188011</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm 1 (ceritinib MTD then with gemcitabine alone)</arm_group_label>
    <arm_group_label>Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)</arm_group_label>
    <arm_group_label>Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel Albumin-Stabilized Nanoparticle Formulation</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)</arm_group_label>
    <other_name>ABI 007</other_name>
    <other_name>ABI-007</other_name>
    <other_name>Abraxane</other_name>
    <other_name>Albumin-bound Paclitaxel</other_name>
    <other_name>Albumin-Stabilized Nanoparticle Paclitaxel</other_name>
    <other_name>nab-paclitaxel</other_name>
    <other_name>Nanoparticle Albumin-bound Paclitaxel</other_name>
    <other_name>Nanoparticle Paclitaxel</other_name>
    <other_name>protein-bound paclitaxel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm 1 (ceritinib MTD then with gemcitabine alone)</arm_group_label>
    <arm_group_label>Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)</arm_group_label>
    <arm_group_label>Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Arm 1: histologically or cytologically confirmed solid tumors that are advanced that&#xD;
             gemcitabine-based treatment is considered a clinically appropriate option&#xD;
&#xD;
          -  Arm 2: histologically or cytologically confirmed adenocarcinoma of the pancreas that&#xD;
             is locally advanced or metastatic&#xD;
&#xD;
          -  Arm 3: histologically or cytologically confirmed solid tumors that are advanced that&#xD;
             gemcitabine plus cisplatin treatment is considered a clinically appropriate option&#xD;
&#xD;
          -  Arms 1E, 2E and 3E: solid tumor that demonstrate anaplastic lymphoma kinase (ALK)&#xD;
             positivity; ALK positivity can be assessed using the assays below, and documentation&#xD;
             of ALK positivity using one of the tests below is required&#xD;
&#xD;
               -  Fluorescence in situ hybridization (FISH) test for ALK positivity using the Food&#xD;
                  and Drug Administration (FDA)-approved FISH test (Abbott Molecular Inc), using&#xD;
                  Vysis breakapart probes (defined as 15% or more positive tumor cells); OR&#xD;
&#xD;
               -  Harboring a confirmed ALK positivity, as determined by positivity to the Ventana&#xD;
                  immunohistochemistry (IHC) assay&#xD;
&#xD;
          -  Arms 1E: previously treated with and progressed on gemcitabine-containing therapy&#xD;
&#xD;
          -  Arms 1, 2, 3: patients should have clinically measurable or evaluable malignant&#xD;
             disease&#xD;
&#xD;
          -  Arms 1E, 2E, 3E: patients with at least one measurable site of disease as defined by&#xD;
             Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 that have&#xD;
             not been previously irradiated&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 1&#xD;
&#xD;
          -  Life expectancy &gt;= 3 months&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1,500 cells/mm^3 (system international [SI] units&#xD;
             1.5 x 10^9/L)&#xD;
&#xD;
          -  Platelets &gt;= 100,000 cells/mm^3 (SI units 100 x 10^9/L)&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL (SI units 90 g/L) (in the absence of transfusion within 24 hours&#xD;
             prior to dosing)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and&#xD;
             alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =&lt; 3 x&#xD;
             upper limit of normal (ULN); in patients with known hepatic involvement, AST and ALT&#xD;
             =&lt; 5 x ULN are allowed&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Calculated or measured creatinine clearance (CrCL) &gt;= 60 mL/min using modified&#xD;
             Cockcroft and Gault formula&#xD;
&#xD;
          -  Serum lipase =&lt; 2 x ULN&#xD;
&#xD;
          -  Serum amylase =&lt; 2 x ULN&#xD;
&#xD;
          -  International normalized ratio (INR) =&lt; 1.5; (anticoagulation is allowed if target INR&#xD;
             =&lt; 1.5 on a stable dose of warfarin or on a stable dose of low molecular weight [LMW]&#xD;
             heparin for &gt; 2 weeks at the first dose of study agent)&#xD;
&#xD;
          -  If urinalysis shows proteinuria, 24 hour urine collection is to be performed and the&#xD;
             24 hour urine protein is to be &lt; 2 grams to be eligible&#xD;
&#xD;
          -  Willing and able to comply with scheduled visits, treatment plan and laboratory tests&#xD;
&#xD;
          -  Ability to understand and willingness to sign a written informed consent; a signed&#xD;
             informed consent must be obtained prior to any study specific procedures&#xD;
&#xD;
          -  Patient must consent to the use of their archival tumor tissue for protocol use if&#xD;
             available&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Arms 2, 2E, 3, 3E: patients who previously received &gt; 2 lines of systemic chemotherapy&#xD;
             for advanced or metastatic disease&#xD;
&#xD;
          -  Previous pelvic radiation affecting &gt;= 25% of the bone marrow; patients who received&#xD;
             whole pelvic radiation are excluded&#xD;
&#xD;
          -  Patients who have received the last administration of an anti-cancer therapy including&#xD;
             chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding&#xD;
             nitrosourea, mitomycin-C, targeted therapy and radiation) =&lt; 4 weeks prior to starting&#xD;
             study drug&#xD;
&#xD;
          -  Patients who have received the last administration of nitrosourea or mitomycin-C =&lt; 6&#xD;
             weeks prior to starting study drug&#xD;
&#xD;
          -  Patients who have had radiotherapy =&lt; 4 weeks prior to starting study drug, or =&lt; 2&#xD;
             weeks prior to starting study drug in the case of localized radiotherapy (e.g., for&#xD;
             analgesic purpose or for lytic lesions at risk of fracture)&#xD;
&#xD;
          -  Patients who have received targeted therapy (e.g., sunitinib, sorafenib, pazopanib),&#xD;
             except ALK inhibitors, =&lt; 2 weeks prior to starting study drug&#xD;
&#xD;
          -  Patients who have residual toxicity(-ities) from previous anti-cancer treatment(s)&#xD;
             that is/are clinically significant or &gt; grade 1 are excluded; those whose&#xD;
             toxicity(-ities) improved to grade 1 or better will be eligible&#xD;
&#xD;
          -  The patient is less than 5 half-lives from prior ALK inhibitor or targeted therapy&#xD;
             (for adequate wash-out) without recovery from treatment toxicities to &lt; grade 1 or to&#xD;
             their pre-treatment levels&#xD;
&#xD;
          -  Patients with known history of extensive disseminated bilateral interstitial fibrosis&#xD;
             or interstitial lung disease, including a history of pneumonitis, hypersensitivity&#xD;
             pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically&#xD;
             significant radiation pneumonitis (i.e., affecting activities of daily living or&#xD;
             requiring therapeutic intervention)&#xD;
&#xD;
          -  Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or&#xD;
             intra-pelvic), open biopsy or significant traumatic injury =&lt; 4 weeks prior to&#xD;
             starting study drug, or patients who have had minor procedures, percutaneous biopsies&#xD;
             or placement of vascular access device =&lt; 1 week prior to starting study drug, or who&#xD;
             have not recovered from side effects of such procedure or injury&#xD;
&#xD;
          -  Known hypersensitivity or infusion reaction to cisplatin and gemcitabine&#xD;
&#xD;
          -  Patients with known hypersensitivity to any of the excipients of ceritinib&#xD;
             (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and&#xD;
             magnesium stearate)&#xD;
&#xD;
          -  Receiving medications that meet one of the following criteria and that cannot be&#xD;
             discontinued at least 1 week prior to the start of treatment with ceritinib and for&#xD;
             the duration of participation:&#xD;
&#xD;
               -  Medication with a known risk of prolonging the QT interval or inducing torsades&#xD;
                  de pointes&#xD;
&#xD;
               -  Strong inhibitors or strong inducers of cytochrome P450, family 3, subfamily A,&#xD;
                  polypeptide 4 (CYP3A4)/5&#xD;
&#xD;
               -  Medications with a low therapeutic index that are primarily metabolized by&#xD;
                  CYP3A4/5, cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) and/or&#xD;
                  cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9)&#xD;
&#xD;
               -  Therapeutic doses (defined as doses need to achieve target INR &gt; 1.5) of warfarin&#xD;
                  sodium (Coumadin) or any other Coumadin-derived anti-coagulant; anticoagulants&#xD;
                  not derived from warfarin are allowed (e.g., dabigatran, rivaroxaban, apixaban)&#xD;
&#xD;
               -  Unstable or increasing doses of corticosteroids&#xD;
&#xD;
               -  Enzyme-inducing anticonvulsive agents&#xD;
&#xD;
               -  Herbal supplements&#xD;
&#xD;
          -  Any of the following concurrent severe and/or uncontrolled medical conditions which&#xD;
             could compromise participation in the study; impaired cardiac function or clinically&#xD;
             significant cardiac diseases, including any of the following:&#xD;
&#xD;
               -  Unstable angina within 6 months prior to screening&#xD;
&#xD;
               -  Myocardial infarction within 6 months prior to screening&#xD;
&#xD;
               -  History of documented congestive heart failure (New York Heart Association&#xD;
                  functional classification III - IV)&#xD;
&#xD;
               -  Uncontrolled hypertension defined by a systolic blood pressure (SBP) &gt;= 160 mm Hg&#xD;
                  and/or diastolic blood pressure (DBP) &gt;= 100 mm Hg, with or without&#xD;
                  antihypertensive medication&#xD;
&#xD;
               -  Initiation or adjustment of antihypertensive medication(s) is allowed prior to&#xD;
                  screening&#xD;
&#xD;
               -  Ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled&#xD;
                  with medication&#xD;
&#xD;
               -  Other cardiac arrhythmia not controlled with medication&#xD;
&#xD;
               -  Corrected QT (QTc) &gt; 450 msec using Fridericia correction on the screening&#xD;
                  electrocardiogram (ECG)&#xD;
&#xD;
          -  Any active gastrointestinal (GI) impairment which, in the opinion of the investigator,&#xD;
             would impair or alter the absorption of ceritinib (e.g., ulcerative colitis, or&#xD;
             Crohn's disease)&#xD;
&#xD;
          -  Ongoing GI adverse events &gt; grade 2 (e.g., nausea, vomiting, or diarrhea) at the start&#xD;
             of the study&#xD;
&#xD;
          -  History of alcoholism, drug addiction, or any psychiatric or psychological condition&#xD;
             which, in the opinion of the investigator, would impair study compliance&#xD;
&#xD;
          -  Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,&#xD;
             active or uncontrolled infection) that could cause unacceptable safety risks or&#xD;
             compromise compliance with the protocol&#xD;
&#xD;
          -  Pregnant or breast-feeding women&#xD;
&#xD;
          -  Women of child-bearing potential, defined as sexually mature women who have not&#xD;
             undergone a hysterectomy or who have not been naturally postmenopausal for at least 12&#xD;
             consecutive months (e.g., who has had menses any time in the preceding 12 consecutive&#xD;
             months), must have a negative serum pregnancy test =&lt; 3 days prior to starting study&#xD;
             treatment&#xD;
&#xD;
          -  Women of child-bearing potential, who are biologically able to conceive, not employing&#xD;
             2 forms of highly effective contraception; male not using at least at least one form&#xD;
             of highly effective contraception will be excluded; highly effective contraception&#xD;
             (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device)&#xD;
             must be used by both sexes during the study and must be continued for 3 months after&#xD;
             the end of study treatment; oral, implantable, or injectable contraceptives may be&#xD;
             affected by cytochrome P450 interactions, and are therefore not considered effective&#xD;
             for this study&#xD;
&#xD;
          -  Patients with untreated brain metastases or who have signs/symptoms attributable to&#xD;
             brain metastases and have not been assessed with radiologic imaging to rule out the&#xD;
             presence of brain metastases; patients with brain metastases that have been&#xD;
             definitively treated and on stable or decreasing dose of steroid within 4 weeks of&#xD;
             starting study treatment will be eligible&#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>Renuka Iyer</last_name>
    <role>Principal Investigator</role>
    <affiliation>Roswell Park Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>August 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <last_update_submitted>July 20, 2022</last_update_submitted>
  <last_update_submitted_qc>July 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic 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>Albumin-Bound Paclitaxel</mesh_term>
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Ceritinib</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02227940
org study id: I 248813
secondary id: NCI-2014-01766
secondary id: I 248813
nct id: NCT02227940
lead sponsor: 
collaborator: 
has dmc: Yes
This phase I trial studies the side effects and best dose of ceritinib and combination
      chemotherapy in treating patients with solid tumors that have spread to other places in the
      body and usually cannot be cured or controlled with treatment (advanced) or pancreatic cancer
      that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or
      has spread to other places in the body (metastatic). Ceritinib may stop the growth of tumor
      cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy,
      such as gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation,
      and cisplatin, work in different ways to stop the growth of tumor cells, either by killing
      the cells, by stopping them from dividing, or by stopping them from spreading. Giving
      ceritinib and more than one drug (combination chemotherapy) may be a better treatment for
      solid tumors or pancreatic cancer.
PRIMARY OBJECTIVES:

      I. Determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of
      ceritinib in combination with gemcitabine (gemcitabine hydrochloride) alone,
      gemcitabine/nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) and
      gemcitabine/cisplatin in patients with advanced solid malignancies.

      SECONDARY OBJECTIVES:

      I. Characterize the safety profile of ceritinib in combination with gemcitabine based
      chemotherapy in advanced solid malignancies.

      II. Determine the pharmacokinetic profile of ceritinib, gemcitabine, nab-paclitaxel,
      cisplatin and their metabolites when administered in combination in patients with advanced
      solid tumors.

      III. Determine the preliminary efficacy of the study combinations.

      TERTIARY OBJECTIVES:

      I. Explore potential biomarkers of efficacy to the study combination.

      OUTLINE: This is a dose-escalation study of ceritinib. Patients are assigned to 1 of 3
      treatment arms.

      ARM 1 (ceritinib MTD then with gemcitabine alone):

      Dose Escalation Cohort 1: Patients with advanced solid tumors for whom gemcitabine
      hydrochloride-based therapy is clinically appropriate receive ceritinib orally (PO) once
      daily (QD) on days 1-28 and gemcitabine hydrochloride intravenously (IV) over 30 minutes on
      days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or
      unacceptable toxicity.

      Expansion Cohort 1E: Once the MTD of ceritinib has been determined, an additional 10 patients
      with anaplastic lymphoma kinase positive (ALK-positive) advanced solid tumors who previously
      progressed on gemcitabine hydrochloride-based therapy receive ceritinib and gemcitabine
      hydrochloride as in the dose escalation cohort 1. Courses repeat every 28 days in the absence
      of disease progression or unacceptable toxicity.

      ARM 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel):

      Dose Escalation Cohort 2: Patients with advanced pancreatic cancer receive ceritinib PO QD on
      days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and paclitaxel
      albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      Expansion Cohort 2E: Once the MTD of ceritinib has been determined, patients with
      ALK-positive advanced solid tumors receive ceritinib, gemcitabine hydrochloride, and
      paclitaxel albumin-stabilized nanoparticle formulation as in the dose escalation cohort 2.
      Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      ARM 3 (ceritinib MTD then with gemcitabine and cisplatin):

      Dose Escalation Cohort 3: Patients with advanced solid tumors for whom gemcitabine
      hydrochloride and cisplatin-based therapy is clinically appropriate receive ceritinib PO QD
      on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and cisplatin IV
      on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable
      toxicity.

      Expansion Cohort 3E: Once the MTD of ceritinib has been determined, an additional 10 patients
      with ALK-positive advanced solid tumors receive ceritinib, gemcitabine hydrochloride, and
      cisplatin as in the dose escalation cohort 3. Courses repeat every 21 days in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for at least 4 weeks.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: MTD and RP2D of ceritinib in combination with gemcitabine hydrochloride alone, defined as the highest dose level at which < 2 of 6 patients experience treatment-related dose limiting toxicity (DLT) (Arms 1 and 1E)
time frame: Up to day 28
description: Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0. The frequency of toxicities will be tabulated for the dose estimated to be the MTD.
measure: MTD and RP2D of ceritinib in combination with gemcitabine hydrochloride and cisplatin, defined as the highest dose level at which < 2 of 6 patients experience treatment-related DLT (Arms 3 and 3E)
time frame: Up to day 28
description: Graded according to NCI CTCAE v4.0. The frequency of toxicities will be tabulated for the dose estimated to be the MTD.
measure: MTD and RP2D of ceritinib in combination with gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation, defined as the highest dose level at which < 2 of 6 patients experience treatment-related DLT (Arms 2 and 2E)
time frame: Up to day 28
description: Graded according to NCI CTCAE v4.0. The frequency of toxicities will be tabulated for the dose estimated to be the MTD.
measure: Incidence of adverse events of ceritinib in combination with gemcitabine hydrochloride based chemotherapy in advanced solid malignancies according to NCI CTCAE v4.0
time frame: Up to 4 weeks after end of treatment
description: Overall safety profile characterized by type, frequency, severity, timing, seriousness and relationship to study treatment. The frequency of toxicities will be tabulated by grade across all dose levels and cycles.
measure: Pharmacokinetic parameters of ceritinib and gemcitabine hydrochloride when administered in combination in patients with advanced solid tumors (Arms 1 and 1E)
time frame: Pre-dose, 0.5, 1-2, 4-5, 6-8, and 24 hours (day 1 of courses 1-2), pre-dose on day 15 of course 1 (ceritinib); prior to end of infusion, 0.5, 1-2, and 4-6 hours post-end of infusion (day 1 of courses 1-2) (gemcitabine hydrochloride)
description: A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual area under the curve (AUC) or clearance (CL) of ceritinib in combination with gemcitabine hydrochloride. The effects of the cytotoxics on ceritinib pharmacokinetic will be evaluated by the model, along with other patient factors that may explain the interpatient variability in pharmacokinetics, including AUC and observed maximum concentration (Cmax).
measure: Pharmacokinetic parameters of ceritinib, gemcitabine hydrochloride, and paclitaxel albumin-stabilized nanoparticle formulation when administered in combination in patients with advanced solid tumors (Arms 2 and 2E)
time frame: Pre-dose, 0.5, 1-2, 4-5, 6-8, and 24 hours (day 1 of courses 1-2), pre-dose on day 15 of course 1 (ceritinib); prior to end of infusion, 0.5, 1-2, and 4-6 hours post-end of infusion (day 1 of courses 1-2) (gemcitabine hydrochloride and nab-paclitaxel)
description: A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual AUCs or CL of ceritinib in combination with gemcitabine hydrochloride and nab-paclitaxel. The effects of the cytotoxics on ceritinib pharmacokinetic will be evaluated by the model, along with other patient factors that may explain the interpatient variability in pharmacokinetics, including AUC and observed Cmax.
measure: Pharmacokinetic parameters of paclitaxel albumin-stabilized nanoparticle formulation, and cisplatin when administered in combination in patients with advanced solid tumors (Arms 3 and 3E)
time frame: Pre-dose, 0.5, 1-2, 4-5, 6-8, and 24 hours (day 1 of courses 1-2), pre-dose on day 15 of course 1 (ceritinib); prior to end of infusion, 0.5, 1-2, and 4-6 hours post-end of infusion (day 1 of courses 1-2) (gemcitabine hydrochloride and cisplatin)
description: A population pharmacokinetic model will be developed utilizing the pharmacokinetic time points collected, and then used to estimate individual AUCs or CL of ceritinib in combination with gemcitabine hydrochloride and cisplatin. The effects of the cytotoxics on ceritinib pharmacokinetic will be evaluated by the model, along with other patient factors that may explain the interpatient variability in pharmacokinetics, including AUC and observed Cmax.
measure: Progression free survival
time frame: Up to 4 weeks after end of treatment
measure: Response rate as assessed by the RECIST 1.1
time frame: Up to 4 weeks after end of treatment
description: Objective tumor response will be tabulated overall (and by dose level if appropriate).
measure: Levels of serum and tumor biomarkers
time frame: Up to 4 weeks after end of treatment
description: The relationship between ALK positivity and antitumor effects will be analyzed descriptively and simple statistics if need to.
arm group label: Arm 1 (ceritinib MTD then with gemcitabine alone)
arm group type: Experimental
description: Dose Escalation Cohort 1: Patients with advanced solid tumors for whom gemcitabine hydrochloride-based therapy is clinically appropriate receive ceritinib PO (QD on days 1-28 and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Expansion Cohort 1E: Once the MTD of ceritinib has been determined, an additional 10 patients with ALK-positive advanced solid tumors who previously progressed on gemcitabine hydrochloride-based therapy receive ceritinib and gemcitabine hydrochloride as in the dose escalation cohort 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
arm group label: Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)
arm group type: Experimental
description: Dose Escalation Cohort 2: Patients with advanced pancreatic cancer receive ceritinib PO QD on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, and paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Expansion Cohort 2E: Once the MTD of ceritinib has been determined, patients with ALK-positive advanced solid tumors receive ceritinib, gemcitabine hydrochloride, and paclitaxel albumin-stabilized nanoparticle formulation as in the dose escalation cohort 2. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
arm group label: Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)
arm group type: Experimental
description: Dose Escalation Cohort 3: Patients with advanced solid tumors for whom gemcitabine hydrochloride and cisplatin-based therapy is clinically appropriate receive ceritinib PO QD on days 1-28, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and cisplatin IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Expansion Cohort 3E: Once the MTD of ceritinib has been determined, an additional 10 patients with ALK-positive advanced solid tumors receive ceritinib, gemcitabine hydrochloride, and cisplatin as in the dose escalation cohort 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Ceritinib
description: Given PO
arm group label: Arm 1 (ceritinib MTD then with gemcitabine alone)
arm group label: Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)
arm group label: Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)
other name: LDK 378
other name: LDK378
other name: Zykadia
intervention type: Drug
intervention name: Cisplatin
description: Given IV
arm group label: Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)
other name: Abiplatin
other name: Blastolem
other name: Briplatin
other name: CDDP
other name: Cis-diammine-dichloroplatinum
other name: Cis-diamminedichloridoplatinum
other name: Cis-diamminedichloro Platinum (II)
other name: Cis-diamminedichloroplatinum
other name: Cis-dichloroammine Platinum (II)
other name: Cis-platinous Diamine Dichloride
other name: Cis-platinum
other name: Cis-platinum II
other name: Cis-platinum II Diamine Dichloride
other name: Cismaplat
other name: Cisplatina
other name: Cisplatinum
other name: Cisplatyl
other name: Citoplatino
other name: Citosin
other name: Cysplatyna
other name: DDP
other name: Lederplatin
other name: Metaplatin
other name: Neoplatin
other name: Peyrone's Chloride
other name: Peyrone's Salt
other name: Placis
other name: Plastistil
other name: Platamine
other name: Platiblastin
other name: Platiblastin-S
other name: Platinex
other name: Platinol
other name: Platinol- AQ
other name: Platinol-AQ
other name: Platinol-AQ VHA Plus
other name: Platinoxan
other name: Platinum
other name: Platinum Diamminodichloride
other name: Platiran
other name: Platistin
other name: Platosin
intervention type: Drug
intervention name: Gemcitabine Hydrochloride
description: Given IV
arm group label: Arm 1 (ceritinib MTD then with gemcitabine alone)
arm group label: Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)
arm group label: Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)
other name: dFdCyd
other name: Difluorodeoxycytidine Hydrochloride
other name: Gemzar
other name: LY-188011
other name: LY188011
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm 1 (ceritinib MTD then with gemcitabine alone)
arm group label: Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)
arm group label: Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)
intervention type: Drug
intervention name: Paclitaxel Albumin-Stabilized Nanoparticle Formulation
description: Given IV
arm group label: Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)
other name: ABI 007
other name: ABI-007
other name: Abraxane
other name: Albumin-bound Paclitaxel
other name: Albumin-Stabilized Nanoparticle Paclitaxel
other name: nab-paclitaxel
other name: Nanoparticle Albumin-bound Paclitaxel
other name: Nanoparticle Paclitaxel
other name: protein-bound paclitaxel
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Arm 1 (ceritinib MTD then with gemcitabine alone)
arm group label: Arm 2 (ceritinib MTD then with gemcitabine and nab-paclitaxel)
arm group label: Arm 3 (ceritinib MTD then with gemcitabine and cisplatin)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Renuka Iyer
role: Principal Investigator
affiliation: Roswell Park Cancer Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
mesh term: Paclitaxel
mesh term: Albumin-Bound Paclitaxel
mesh term: Cisplatin
mesh term: Gemcitabine
mesh term: Ceritinib