<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/NCT03771820</url>
  </required_header>
  <id_info>
    <org_study_id>NC-6004-009</org_study_id>
    <nct_id>NCT03771820</nct_id>
  </id_info>
  <brief_title>Combination Therapy With NC-6004 and Pembrolizumab in Head and Neck Cancer Subjects Who Have Failed Platinum Regimen</brief_title>
  <official_title>Phase IIa/IIb Clinical Trial of NC-6004 in Combination With Pembrolizumab in Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Who Have Failed Platinum or a Platinum-containing Regimen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NanoCarrier Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Orient Europharma Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>NanoCarrier Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</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 Phase IIa, dose-escalation study to determine the optimum tolerated dose and a recommended&#xD;
      Phase IIb (RPIIb) dose in combination with pembrolizumab in subjects with recurrent or&#xD;
      metastatic squamous cell carcinoma of the head and neck who have failed platinum or a&#xD;
      platinum containing regimen.&#xD;
&#xD;
      In Phase IIb, randomized control study between NC-6004 in combination with pembrolizumab&#xD;
      versus pembrolizumab alone in the same subject population as Part 1 at the RPIIb dose&#xD;
      identified in PIIa.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 1, 2019</start_date>
  <completion_date type="Anticipated">April 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2021</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>Determine the Recommended Phase (RPII) dose (mg/m2) of NC-6004 in combination with pembrolizumab</measure>
    <time_frame>1 year</time_frame>
    <description>In PIIa portion, to determine RPII dose of NC-6004 in combination with pembrolizumab</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Compare median Progression Free Survival (PFS) between NC-6004 +pembrolizumab and pembrolizumab alone</measure>
    <time_frame>1 year</time_frame>
    <description>In PIIb portion, to compare PFS between NC-6004 plus pembrolizumab and pembrolizumab alone.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare median Overall Survival (OS) between NC-6004 +pembrolizumab and pembrolizumab alone</measure>
    <time_frame>2 years</time_frame>
    <description>In PIIb portion, to compare OS rate between NC-6004 plus pembrolizumab and pembrolizumab alone.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare overall response (complete response and partial response) rate between NC-6004 +pembrolizumab and pembrolizumab alone</measure>
    <time_frame>1 year</time_frame>
    <description>In PIIb portion, to ORR between NC-6004 plus pembrolizumab and pembrolizumab alone</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare duration of response between NC-6004 +pembrolizumab and pembrolizumab alone</measure>
    <time_frame>1 year</time_frame>
    <description>In PIIb portion, to compare DOR between NC-6004 plus pembrolizumab and pembrolizumab alone</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare time to response between NC-6004 +pembrolizumab and pembrolizumab alone</measure>
    <time_frame>1 year</time_frame>
    <description>In PIIb portion, to compare TTR between NC-6004 plus pembrolizumab and pembrolizumab alone</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability as measured by severity of Adverse Events (AEs)</measure>
    <time_frame>1 year</time_frame>
    <description>The safety endpoints for this study are the incidence and severity of AEs in accordance with the NCI CTCAE and the occurrence of SAEs and treatment discontinuations due to AEs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the Maximum Plasma Concentration (Cmax) of NC-6004 in combination with pembrolizumab</measure>
    <time_frame>1 year</time_frame>
    <description>Assess PK parameters of the Maximum Plasma Concentration (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the Time to Maximum Concentration (Tmax) of NC-6004 in combination with pembrolizumab</measure>
    <time_frame>1 year</time_frame>
    <description>Assess PK parameters of Time to Maximum Concentration (Tmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the Area Under the Concentration (AUC) of NC-6004 in combination with pembrolizumab</measure>
    <time_frame>1 year</time_frame>
    <description>Assess PK parameters of Area Under the Concentration (AUC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the Half-life(T½) of NC-6004 in combination with pembrolizumab</measure>
    <time_frame>1 year</time_frame>
    <description>Assess PK parameters of Half-life(T½)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the Clearance (CL) of NC-6004 in combination with pembrolizumab</measure>
    <time_frame>1 year</time_frame>
    <description>Assess PK parameters of Clearance (CL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the Volume of Distribution (V) of NC-6004 in combination with pembrolizumab</measure>
    <time_frame>1 year</time_frame>
    <description>Assess PK parameters of Volume of Distribution (V)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">136</enrollment>
  <condition>SCCHN</condition>
  <arm_group>
    <arm_group_label>NC-6004 +pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NC-6004 should be administered to subjects once every 3 weeks. On Day 1 of each treatment cycle NC-6004 will be administered first followed by pembrolizumab.&#xD;
In phase IIa portion, NC-6004 dose goes up from 90 mg/m2 up to 135 mg/m2. In phase IIb portion, the dose should be the determined RPII dose in phase IIa portion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The recommended dose of pembrolizumab is 200 mg administered as an IV infusion over 30 minutes every 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NC-6004</intervention_name>
    <description>NC-6004 should be administered to subjects once every 3 weeks. On Day 1 of each treatment cycle NC-6004 will be administered first followed by pembrolizumab.</description>
    <arm_group_label>NC-6004 +pembrolizumab</arm_group_label>
    <other_name>Nanoplatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>The recommended dose of pembrolizumab is 200 mg administered as an IV infusion over 30 minutes every 3 weeks.</description>
    <arm_group_label>NC-6004 +pembrolizumab</arm_group_label>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be willing and able to provide written informed consent for the trial.&#xD;
&#xD;
          -  Males or females aged ≥18 years at screening.&#xD;
&#xD;
          -  Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.&#xD;
&#xD;
          -  Have histologically- or cytologically-confirmed HNSCC.&#xD;
&#xD;
          -  Have recurrent disease not amenable to curative treatment with local or systemic&#xD;
             therapy, or metastatic (disseminated) HNSCC of the oral cavity, oropharynx,&#xD;
             hypopharynx, or larynx that is considered incurable by local therapies.&#xD;
&#xD;
          -  Having prior platinum failure.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary&#xD;
             origination, squamous cell carcinoma that originates from the skin and salivary gland&#xD;
             or paranasal sinus, nonsquamous histologies.&#xD;
&#xD;
          -  Have disease that is suitable for locoregional treatment administered with curative&#xD;
             intent or refuses curative intent.&#xD;
&#xD;
          -  Have no more than 15% body weight loss due to the underlying condition in the last 3&#xD;
             months from signing of informed consent in Part 1 of the study and from randomization&#xD;
             in to Part 2.&#xD;
&#xD;
          -  Are currently participating in or have participated in a study of an investigational&#xD;
             agent or are using an investigational device within 4 weeks prior to the first dose of&#xD;
             trial treatment.&#xD;
&#xD;
          -  Were previously treated with 3 or more lines of systemic therapies administered for&#xD;
             recurrent and/or metastatic disease.&#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>Atsushi Osada</last_name>
    <role>Study Director</role>
    <affiliation>NanoCarrier US LLC</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Atsushi Osada</last_name>
    <phone>781 219 4958</phone>
    <email>osada@nanocarrier.co.jp</email>
  </overall_contact>
  <location>
    <facility>
      <name>0603</name>
      <address>
        <city>Osijek</city>
        <country>Croatia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0601</name>
      <address>
        <city>Zagreb</city>
        <country>Croatia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0602</name>
      <address>
        <city>Zagreb</city>
        <country>Croatia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0701</name>
      <address>
        <city>Brno</city>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0702</name>
      <address>
        <city>Hradec Králové</city>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0703</name>
      <address>
        <city>Olomouc</city>
        <country>Czechia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0104</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0105</name>
      <address>
        <city>Debrecen</city>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0103</name>
      <address>
        <city>Kecskemét</city>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0101</name>
      <address>
        <city>Pécs</city>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0202</name>
      <address>
        <city>Bydgoszcz</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0201</name>
      <address>
        <city>Łódź</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0801</name>
      <address>
        <city>Ekaterinburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0802</name>
      <address>
        <city>Omsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0301</name>
      <address>
        <city>Belgrade</city>
        <country>Serbia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0303</name>
      <address>
        <city>Niš</city>
        <country>Serbia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0301</name>
      <address>
        <city>Sremska Kamenica</city>
        <country>Serbia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0404</name>
      <address>
        <city>Taichung City</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0402</name>
      <address>
        <city>Taipei city</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0403</name>
      <address>
        <city>Taipei city</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0401</name>
      <address>
        <city>Taoyuan City</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0902</name>
      <address>
        <city>Cherkasy</city>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0903</name>
      <address>
        <city>Ivano-Frankivs'k</city>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>0904</name>
      <address>
        <city>Kharkiv</city>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Croatia</country>
    <country>Czechia</country>
    <country>Hungary</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Serbia</country>
    <country>Taiwan</country>
    <country>Ukraine</country>
  </location_countries>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>November 1, 2018</study_first_submitted>
  <study_first_submitted_qc>December 9, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>March 15, 2021</last_update_submitted>
  <last_update_submitted_qc>March 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03771820
org study id: NC-6004-009
nct id: NCT03771820
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
In Phase IIa, dose-escalation study to determine the optimum tolerated dose and a recommended
      Phase IIb (RPIIb) dose in combination with pembrolizumab in subjects with recurrent or
      metastatic squamous cell carcinoma of the head and neck who have failed platinum or a
      platinum containing regimen.

      In Phase IIb, randomized control study between NC-6004 in combination with pembrolizumab
      versus pembrolizumab alone in the same subject population as Part 1 at the RPIIb dose
      identified in PIIa.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Determine the Recommended Phase (RPII) dose (mg/m2) of NC-6004 in combination with pembrolizumab
time frame: 1 year
description: In PIIa portion, to determine RPII dose of NC-6004 in combination with pembrolizumab
measure: Compare median Progression Free Survival (PFS) between NC-6004 +pembrolizumab and pembrolizumab alone
time frame: 1 year
description: In PIIb portion, to compare PFS between NC-6004 plus pembrolizumab and pembrolizumab alone.
measure: Compare median Overall Survival (OS) between NC-6004 +pembrolizumab and pembrolizumab alone
time frame: 2 years
description: In PIIb portion, to compare OS rate between NC-6004 plus pembrolizumab and pembrolizumab alone.
measure: Compare overall response (complete response and partial response) rate between NC-6004 +pembrolizumab and pembrolizumab alone
time frame: 1 year
description: In PIIb portion, to ORR between NC-6004 plus pembrolizumab and pembrolizumab alone
measure: Compare duration of response between NC-6004 +pembrolizumab and pembrolizumab alone
time frame: 1 year
description: In PIIb portion, to compare DOR between NC-6004 plus pembrolizumab and pembrolizumab alone
measure: Compare time to response between NC-6004 +pembrolizumab and pembrolizumab alone
time frame: 1 year
description: In PIIb portion, to compare TTR between NC-6004 plus pembrolizumab and pembrolizumab alone
measure: Safety and tolerability as measured by severity of Adverse Events (AEs)
time frame: 1 year
description: The safety endpoints for this study are the incidence and severity of AEs in accordance with the NCI CTCAE and the occurrence of SAEs and treatment discontinuations due to AEs
measure: Assess the Maximum Plasma Concentration (Cmax) of NC-6004 in combination with pembrolizumab
time frame: 1 year
description: Assess PK parameters of the Maximum Plasma Concentration (Cmax)
measure: Assess the Time to Maximum Concentration (Tmax) of NC-6004 in combination with pembrolizumab
time frame: 1 year
description: Assess PK parameters of Time to Maximum Concentration (Tmax)
measure: Assess the Area Under the Concentration (AUC) of NC-6004 in combination with pembrolizumab
time frame: 1 year
description: Assess PK parameters of Area Under the Concentration (AUC)
measure: Assess the Half-life(T½) of NC-6004 in combination with pembrolizumab
time frame: 1 year
description: Assess PK parameters of Half-life(T½)
measure: Assess the Clearance (CL) of NC-6004 in combination with pembrolizumab
time frame: 1 year
description: Assess PK parameters of Clearance (CL)
measure: Assess the Volume of Distribution (V) of NC-6004 in combination with pembrolizumab
time frame: 1 year
description: Assess PK parameters of Volume of Distribution (V)
arm group label: NC-6004 +pembrolizumab
arm group type: Experimental
description: NC-6004 should be administered to subjects once every 3 weeks. On Day 1 of each treatment cycle NC-6004 will be administered first followed by pembrolizumab.
In phase IIa portion, NC-6004 dose goes up from 90 mg/m2 up to 135 mg/m2. In phase IIb portion, the dose should be the determined RPII dose in phase IIa portion.
arm group label: Pembrolizumab
arm group type: Active Comparator
description: The recommended dose of pembrolizumab is 200 mg administered as an IV infusion over 30 minutes every 3 weeks.
intervention type: Drug
intervention name: NC-6004
description: NC-6004 should be administered to subjects once every 3 weeks. On Day 1 of each treatment cycle NC-6004 will be administered first followed by pembrolizumab.
arm group label: NC-6004 +pembrolizumab
other name: Nanoplatin
intervention type: Drug
intervention name: Pembrolizumab
description: The recommended dose of pembrolizumab is 200 mg administered as an IV infusion over 30 minutes every 3 weeks.
arm group label: NC-6004 +pembrolizumab
arm group label: Pembrolizumab
other name: Keytruda
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Atsushi Osada
role: Study Director
affiliation: NanoCarrier US LLC
last name: Atsushi Osada
phone: 781 219 4958
email: osada@nanocarrier.co.jp
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: Croatia
country: Czechia
country: Hungary
country: Poland
country: Russian Federation
country: Serbia
country: Taiwan
country: Ukraine
country: United States
responsible party type: Sponsor
mesh term: Pembrolizumab
sharing ipd: Undecided