<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/NCT02240238</url>
  </required_header>
  <id_info>
    <org_study_id>NC-6004-004A</org_study_id>
    <nct_id>NCT02240238</nct_id>
  </id_info>
  <brief_title>Combination Therapy With NC-6004 and Gemcitabine in Advanced Solid Tumors or Non-Small Cell Lung, Biliary and Bladder Cancer</brief_title>
  <official_title>A Phase 1b/2 Dose Escalation and Expansion Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients With Advanced Solid Tumors or Non-Small Cell Lung, Biliary Tract, and Bladder Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NanoCarrier Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NanoCarrier Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In the dose escalation phase (Part 1), this study will determine the dose-limiting toxicities&#xD;
      (DLTs), the maximum tolerated dose (MTD) and recommended Phase 2 (RPII) dose of NC 6004 in&#xD;
      combination with gemcitabine.&#xD;
&#xD;
      In the expansion phase of the study (Part 2), study will evaluate the activity, safety, and&#xD;
      tolerability at the RPII dose identified in Part 1 in patients with squamous NSCLC, biliary&#xD;
      tract, and bladder cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2014</start_date>
  <completion_date type="Actual">May 6, 2019</completion_date>
  <primary_completion_date type="Actual">May 6, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open Label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Determine the RPII dose of NC-6004 in combination with gemcitabine</measure>
    <time_frame>1 year</time_frame>
    <description>In the dose-escalation phase of the study (Part 1), to determine the dose-limiting toxicities (DLTs), MTD, and RPII dose of NC-6004 in combination with gemcitabine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Activity of NC-6004 measured by progression-free survival (PFS)</measure>
    <time_frame>1 year</time_frame>
    <description>In the expansion phase of the study (Part 2), to evaluate the activity of NC-6004 in combination with gemcitabine in patients with first-line Stage IV squamous NSCLC, first-line advanced or metastatic biliary tract cancer, and first-line metastatic or locally advanced bladder cancer compared with historical control as measured by local investigator/radiologist-assessed progression-free survival (PFS), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>every 6 weeks tumor assessments for response and disease progression after treatment discontinuation and telephone calls for survival every 12 weeks until disease progression.</time_frame>
    <description>To evaluate ORR, DCR (DCR = complete response [CR] + partial response [PR] + stable disease [SD]), DOR, PFS, and OS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Therapy-related AEs</measure>
    <time_frame>1 year</time_frame>
    <description>Incidence and severity of therapy-related AEs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EORTC QLQ-C30</measure>
    <time_frame>1 year</time_frame>
    <description>To evaluate QoL using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability as measured by severity of AEs and laboratory abnormalities</measure>
    <time_frame>1 year</time_frame>
    <description>The safety endpoints for this study are the incidence and severity of AEs and laboratory abnormalities, according to the NCI CTCAE version 4.03, the occurrence of SAEs and treatment discontinuations due to AEs, and nausea severity and vomiting incidence obtained from the patient diary</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">209</enrollment>
  <condition>Solid Tumors</condition>
  <arm_group>
    <arm_group_label>NC-6004 and Gemcitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NC-6004</intervention_name>
    <description>NC-6004 - given at escalating doses of 60, 75, 90, 105, 120, 135, 150, 165, or 180 mg/m2 according to observations of dose-limiting toxicity.</description>
    <arm_group_label>NC-6004 and Gemcitabine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Gemcitabine 1250 mg/m2 will be administered as a 30 minute intravenous infusion on Day 1 after the completion of the NC 6004 infusion and on Day 8 of each cycle.</description>
    <arm_group_label>NC-6004 and Gemcitabine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  (Part 1 only) Have a histologically or cytologically confirmed diagnosis of advanced&#xD;
             solid tumor that has relapsed or is refractory to standard curative or palliative&#xD;
             therapy or has a contraindication to standard therapy.&#xD;
&#xD;
          -  (Part 2 only) Cohort 1: Have histologically or cytologically confirmed diagnosis of&#xD;
             Stage IV squamous NSCLC and have not received prior chemotherapy or immunotherapy for&#xD;
             metastatic disease and are not known to be PD-L1 positive (known high PD-L1 expression&#xD;
             defined as Tumor Proportion Score [TPS] greater than or equal to 50%). Patients with&#xD;
             known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or&#xD;
             anaplastic lymphoma kinase (ALK) fusion oncogene must have received at least 1 and up&#xD;
             to 2 targeted therapies prior to enrollment.&#xD;
&#xD;
          -  (Part 2 only) Cohort 2: Have histologically or cytologically confirmed diagnosis of&#xD;
             nonresectable, recurrent, or metastatic biliary tract carcinoma (intrahepatic or&#xD;
             extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary carcinoma) and have&#xD;
             not received prior systemic anticancer therapy for advanced or metastatic disease.&#xD;
&#xD;
          -  (Part 2 only) Cohort 3: Have histologically or cytologically confirmed diagnosis of&#xD;
             metastatic or locally advanced TCC of the urinary tract (bladder, urethra, ureter,&#xD;
             renal pelvis) (T3b-T4 N0 M0, Tany N1-N3 M0, or Tany Nany M1) and are not candidates&#xD;
             for surgery.&#xD;
&#xD;
          -  Have measurable disease per RECIST version 1.1.&#xD;
&#xD;
          -  Have an ECOG PS of 0 to 1, with the exception of patients in Part 2 (Cohort 3, unfit&#xD;
             bladder cancer patients) who may have an ECOG PS of 2&#xD;
&#xD;
          -  Adequate bone marrow reserve, liver and renal function&#xD;
&#xD;
          -  Have a negative pregnancy test result at Screening for females of childbearing&#xD;
             potential&#xD;
&#xD;
          -  Male patients must agree to use a condom during treatment and for 90 days after dosing&#xD;
             and must agree not to donate sperm for 90 days after dosing&#xD;
&#xD;
          -  Women of childbearing potential are willing to agree to use 1 of the study defined&#xD;
             effective methods of birth control from the time of study entry to 6 months after the&#xD;
             last day of treatment&#xD;
&#xD;
          -  Reasonably recovered from preceding major surgery as judged by the investigator or no&#xD;
             major surgery within 4 weeks prior to the start of Day 1 treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have received prior platinum therapy in the past 3 months (Part 1) or 6 months in the&#xD;
             adjuvant or neoadjuvant setting (Part 2).&#xD;
&#xD;
          -  Have received prior cisplatin and gemcitabine concomitantly within the last 6 months&#xD;
             or are refractory to cisplatin and gemcitabine.&#xD;
&#xD;
          -  Unresolved toxicity from prior radiation, chemotherapy, or other targeted treatment,&#xD;
             including investigational treatment&#xD;
&#xD;
          -  Have evidence suggesting pulmonary fibrosis or interstitial pneumonia.&#xD;
&#xD;
          -  Have a history of thrombocytopenia with complications&#xD;
&#xD;
          -  Have known hypersensitivity to platinum compounds or gemcitabine.&#xD;
&#xD;
          -  Have uncontrolled diabetes or have hypertension requiring more than 3 medications for&#xD;
             control of hypertension.&#xD;
&#xD;
          -  Have pre-existing alcoholic liver injury or significant liver disease.&#xD;
&#xD;
          -  Pregnant or breast feeding&#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>Joao da Silva, MD</last_name>
    <role>Principal Investigator</role>
  </overall_official>
  <location>
    <facility>
      <name>California Cancer Associates for Research and Excellence</name>
      <address>
        <city>Encinitas</city>
        <state>California</state>
        <zip>92024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC San Diego Moores Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Hematology Oncology Associates</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University Feinberg School of Medicine</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Case Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multiprofile Hospital for Active Treatment Serdika EOOD</name>
      <address>
        <city>Sofia</city>
        <state>Sofia-Grad</state>
        <zip>1632</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complex Oncology Center - Shumen EOOD</name>
      <address>
        <city>Shumen</city>
        <zip>9700</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST</name>
      <address>
        <city>Meldola</city>
        <zip>47014</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda</name>
      <address>
        <city>Milano</city>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie</name>
      <address>
        <city>Krakow</city>
        <zip>31826</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Med-Polonia Sp. z o.o.</name>
      <address>
        <city>Poznan</city>
        <zip>60693</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundeni Clinical Institute</name>
      <address>
        <city>Bucharest</city>
        <zip>22328</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coltea Clinical Hospital</name>
      <address>
        <city>Bucharest</city>
        <zip>30171</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prof Dr I Chiricuta Institute of Oncology</name>
      <address>
        <city>Cluj-Napoca</city>
        <zip>400015</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Center Sfantul Nectarie</name>
      <address>
        <city>Craiova</city>
        <zip>200347</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Euroclinic Oncology Center SRL</name>
      <address>
        <city>Iasi</city>
        <zip>700106</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institutul Regional de Oncologie Iasi</name>
      <address>
        <city>Iasi</city>
        <zip>700483</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Italy</country>
    <country>Poland</country>
    <country>Romania</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Subbiah V, Grilley-Olson JE, Combest AJ, Sharma N, Tran RH, Bobe I, Osada A, Takahashi K, Balkissoon J, Camp A, Masada A, Reitsma DJ, Bazhenova LA. Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors. Clin Cancer Res. 2018 Jan 1;24(1):43-51. doi: 10.1158/1078-0432.CCR-17-1114. Epub 2017 Oct 13.</citation>
    <PMID>29030354</PMID>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <last_update_submitted>February 27, 2020</last_update_submitted>
  <last_update_submitted_qc>February 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 28, 2020</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>Urinary Bladder Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</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/NCT02240238
org study id: NC-6004-004A
nct id: NCT02240238
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
In the dose escalation phase (Part 1), this study will determine the dose-limiting toxicities
      (DLTs), the maximum tolerated dose (MTD) and recommended Phase 2 (RPII) dose of NC 6004 in
      combination with gemcitabine.

      In the expansion phase of the study (Part 2), study will evaluate the activity, safety, and
      tolerability at the RPII dose identified in Part 1 in patients with squamous NSCLC, biliary
      tract, and bladder cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open Label
measure: Determine the RPII dose of NC-6004 in combination with gemcitabine
time frame: 1 year
description: In the dose-escalation phase of the study (Part 1), to determine the dose-limiting toxicities (DLTs), MTD, and RPII dose of NC-6004 in combination with gemcitabine
measure: Activity of NC-6004 measured by progression-free survival (PFS)
time frame: 1 year
description: In the expansion phase of the study (Part 2), to evaluate the activity of NC-6004 in combination with gemcitabine in patients with first-line Stage IV squamous NSCLC, first-line advanced or metastatic biliary tract cancer, and first-line metastatic or locally advanced bladder cancer compared with historical control as measured by local investigator/radiologist-assessed progression-free survival (PFS), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
measure: Overall response rate
time frame: every 6 weeks tumor assessments for response and disease progression after treatment discontinuation and telephone calls for survival every 12 weeks until disease progression.
description: To evaluate ORR, DCR (DCR = complete response [CR] + partial response [PR] + stable disease [SD]), DOR, PFS, and OS
measure: Therapy-related AEs
time frame: 1 year
description: Incidence and severity of therapy-related AEs
measure: EORTC QLQ-C30
time frame: 1 year
description: To evaluate QoL using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
measure: Safety and tolerability as measured by severity of AEs and laboratory abnormalities
time frame: 1 year
description: The safety endpoints for this study are the incidence and severity of AEs and laboratory abnormalities, according to the NCI CTCAE version 4.03, the occurrence of SAEs and treatment discontinuations due to AEs, and nausea severity and vomiting incidence obtained from the patient diary
arm group label: NC-6004 and Gemcitabine
arm group type: Experimental
intervention type: Drug
intervention name: NC-6004
description: NC-6004 - given at escalating doses of 60, 75, 90, 105, 120, 135, 150, 165, or 180 mg/m2 according to observations of dose-limiting toxicity.
arm group label: NC-6004 and Gemcitabine
intervention type: Drug
intervention name: Gemcitabine
description: Gemcitabine 1250 mg/m2 will be administered as a 30 minute intravenous infusion on Day 1 after the completion of the NC 6004 infusion and on Day 8 of each cycle.
arm group label: NC-6004 and Gemcitabine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joao da Silva, MD
role: Principal Investigator
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country: Bulgaria
country: Italy
country: Poland
country: Romania
country: United States
citation: Subbiah V, Grilley-Olson JE, Combest AJ, Sharma N, Tran RH, Bobe I, Osada A, Takahashi K, Balkissoon J, Camp A, Masada A, Reitsma DJ, Bazhenova LA. Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors. Clin Cancer Res. 2018 Jan 1;24(1):43-51. doi: 10.1158/1078-0432.CCR-17-1114. Epub 2017 Oct 13.
PMID: 29030354
responsible party type: Sponsor
mesh term: Urinary Bladder Neoplasms
mesh term: Gemcitabine