<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/NCT02988440</url>
  </required_header>
  <id_info>
    <org_study_id>CPDR001G2101</org_study_id>
    <secondary_id>2016-004131-20</secondary_id>
    <nct_id>NCT02988440</nct_id>
  </id_info>
  <brief_title>Study of Safety and Tolerability of PDR001 in Combination With Sorafenib and to Identify the Maximum Tolerated Dose and/or Phase 2 Dose for This Combination in Advanced Hepatocellular Patients</brief_title>
  <official_title>A Phase Ib Study of PDR001 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</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>
      A two part study to determine the maximum tolerated dose and/or recommended phase 2 dose of&#xD;
      PDR001 in combination with sorafenib in patients with advanced hepatocellular carcinoma in&#xD;
      first line. There will be a dose escalation part and a dose expansion part.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 20, 2017</start_date>
  <completion_date type="Actual">February 27, 2020</completion_date>
  <primary_completion_date type="Actual">February 27, 2020</primary_completion_date>
  <phase>Phase 1</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>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>From baseline until 30 days of last dose of study treatment</time_frame>
    <description>Incidence and severity of AEs and SAEs, including changes in laboratory vital signs and ECGs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidendence of Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>During the first 8 weeks of treatment</time_frame>
    <description>A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose interruptions</measure>
    <time_frame>Until end of treatment, assessed for a median time of 4 months</time_frame>
    <description>Tolerability measured by the number of subjects who have interruptions of study treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose reductions</measure>
    <time_frame>Until end of treatment, assessed for a median time of 4 months</time_frame>
    <description>Tolerability measured by the number of subjects who have reductions of study treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose intensity</measure>
    <time_frame>Until end of treatment, assessed for a median time of 4 months</time_frame>
    <description>Tolerability measured by the dose intensity of study treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as per central radiology assessment by dose level</measure>
    <time_frame>Until end of treatment, assessed for a median time of 4 months</time_frame>
    <description>Overall response rate (ORR) as per the independent central radiology assessment will be summarized descriptively by dose level. The overall response rate (ORR) is defined as the proportion of patients with best overall response of CR or PR. The best overall response is the best response recorded using the independent central radiology review based on RECIST 1.1 from start of treatment until disease progression, death, start of new therapy, withdrawal of consent or cut-off date, whichever occurs first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PDR001 trough concentration</measure>
    <time_frame>Pre-dose at Cycle 2, 3, 4, 6 , 8, 10, 12 on Day 1. Cycle=28 days</time_frame>
    <description>Concentration of PDR001 in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration (Cmax) of sorafenib</measure>
    <time_frame>Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days</time_frame>
    <description>The maximum (peak) observed plasma, drug concentration after single dose administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reach maximum concentration (Tmax) of sorafenib</measure>
    <time_frame>Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days</time_frame>
    <description>The time to reach maximum (peak) plasma drug concentration after single dose administration (time)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve of sorafenib from time zero to 8 hours after administration (AUC0-8)</measure>
    <time_frame>Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days</time_frame>
    <description>Area under the plasma concentration-time curve of sorafenib from time zero to time 't' where t is a defined time point after administration. t=8 hours (AUC0-8)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Profile (AUCtau) of sorafenib</measure>
    <time_frame>Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days</time_frame>
    <description>Area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady-state</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>PDR001 + Sorafenib</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>PDR001 at 400 mg given intravenously every 4 weeks and sorafenib 400 mg taken orally once or twice per day (escalating doses)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PDR001</intervention_name>
    <description>PDR001 will be administered intravenously</description>
    <arm_group_label>PDR001 + Sorafenib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>Sorafenib is formulated as a tablet.</description>
    <arm_group_label>PDR001 + Sorafenib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed advanced (unresectable and/or metastatic)&#xD;
             HCC&#xD;
&#xD;
          -  Patients with advanced HCC not amenable for surgical or loco-regional treatment&#xD;
&#xD;
          -  At least one measureable tumor lesion that that has not been previously locally&#xD;
&#xD;
          -  Patients with current cirrhotic status of Child-Pugh class A only (5-6 points with&#xD;
             total bilirubin &lt; 2 mg/dL for dose-escalation) with no encephalopathy and no clinical&#xD;
             ascites (ascites controlled by diuretics is also excluded in this study).&#xD;
&#xD;
          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Patient must meet required laboratory values at the screening&#xD;
&#xD;
          -  Normal electrocardiogram at screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC&#xD;
&#xD;
          -  Invasion of the main portal vein and/or tumor involvement in more than 50% of the&#xD;
             liver (applicable only for the dose-escalation part)&#xD;
&#xD;
          -  Patients with Portal-caval shunts&#xD;
&#xD;
          -  Prior or concomitant systemic anti-cancer treatment for advanced disease&#xD;
&#xD;
          -  Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any&#xD;
             immunosuppressive therapy 7 days prior to planned date for first dose of study&#xD;
             treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.&#xD;
&#xD;
          -  Cardiac or cardiac repolarization abnormality&#xD;
&#xD;
          -  Patients with active Hepatitis B infection (HBsAg positive) that are not receiving&#xD;
             antiviral treatment are excluded&#xD;
&#xD;
          -  Patients with positive test for hepatitis C ribonucleic acid (HCV RNA)&#xD;
&#xD;
          -  Loco-regional treatment within 4 weeks prior to initiation of study treatment.&#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>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rozzano</city>
        <state>MI</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <zip>277 8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Yokohama city</city>
        <state>Kanagawa</state>
        <zip>232 0024</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pamplona</city>
        <state>Navarra</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Germany</country>
    <country>Hong Kong</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>France</country>
    <country>Switzerland</country>
  </removed_countries>
  <link>
    <url>https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17724</url>
    <description>Results for CPDR001G2101 from Novartis Clinical Trials Website</description>
  </link>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>December 7, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <last_update_submitted>December 16, 2020</last_update_submitted>
  <last_update_submitted_qc>December 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HCC</keyword>
  <keyword>Hepatocellular carcinoma</keyword>
  <keyword>Hepatocellular carcinoma (HCC)</keyword>
  <keyword>PDR001</keyword>
  <keyword>liver cancer</keyword>
  <keyword>immunotherapy liver</keyword>
  <keyword>malignant hepatoma</keyword>
  <keyword>Hepatocellular cancer</keyword>
  <keyword>advanced hepatocellular carcinoma (HCC)</keyword>
  <keyword>advanced liver cancer</keyword>
  <keyword>liver cancer progression</keyword>
  <keyword>sorafenib</keyword>
  <keyword>anti-PD1</keyword>
  <keyword>first line</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sorafenib</mesh_term>
    <mesh_term>Spartalizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02988440
org study id: CPDR001G2101
secondary id: 2016-004131-20
nct id: NCT02988440
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
A two part study to determine the maximum tolerated dose and/or recommended phase 2 dose of
      PDR001 in combination with sorafenib in patients with advanced hepatocellular carcinoma in
      first line. There will be a dose escalation part and a dose expansion part.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: From baseline until 30 days of last dose of study treatment
description: Incidence and severity of AEs and SAEs, including changes in laboratory vital signs and ECGs
measure: Incidendence of Dose Limiting Toxicities (DLTs)
time frame: During the first 8 weeks of treatment
description: A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.
measure: Dose interruptions
time frame: Until end of treatment, assessed for a median time of 4 months
description: Tolerability measured by the number of subjects who have interruptions of study treatment
measure: Dose reductions
time frame: Until end of treatment, assessed for a median time of 4 months
description: Tolerability measured by the number of subjects who have reductions of study treatment
measure: Dose intensity
time frame: Until end of treatment, assessed for a median time of 4 months
description: Tolerability measured by the dose intensity of study treatment
measure: Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as per central radiology assessment by dose level
time frame: Until end of treatment, assessed for a median time of 4 months
description: Overall response rate (ORR) as per the independent central radiology assessment will be summarized descriptively by dose level. The overall response rate (ORR) is defined as the proportion of patients with best overall response of CR or PR. The best overall response is the best response recorded using the independent central radiology review based on RECIST 1.1 from start of treatment until disease progression, death, start of new therapy, withdrawal of consent or cut-off date, whichever occurs first
measure: PDR001 trough concentration
time frame: Pre-dose at Cycle 2, 3, 4, 6 , 8, 10, 12 on Day 1. Cycle=28 days
description: Concentration of PDR001 in plasma
measure: Maximum concentration (Cmax) of sorafenib
time frame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
description: The maximum (peak) observed plasma, drug concentration after single dose administration.
measure: Time to reach maximum concentration (Tmax) of sorafenib
time frame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
description: The time to reach maximum (peak) plasma drug concentration after single dose administration (time)
measure: Area under the plasma concentration-time curve of sorafenib from time zero to 8 hours after administration (AUC0-8)
time frame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
description: Area under the plasma concentration-time curve of sorafenib from time zero to time 't' where t is a defined time point after administration. t=8 hours (AUC0-8)
measure: Area Under the Plasma Concentration-time Profile (AUCtau) of sorafenib
time frame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
description: Area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady-state
arm group label: PDR001 + Sorafenib
arm group type: Other
description: PDR001 at 400 mg given intravenously every 4 weeks and sorafenib 400 mg taken orally once or twice per day (escalating doses)
intervention type: Drug
intervention name: PDR001
description: PDR001 will be administered intravenously
arm group label: PDR001 + Sorafenib
intervention type: Drug
intervention name: Sorafenib
description: Sorafenib is formulated as a tablet.
arm group label: PDR001 + Sorafenib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: Germany
country: Hong Kong
country: Italy
country: Japan
country: Spain
country: Taiwan
country: United States
country: France
country: Switzerland
url: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17724
description: Results for CPDR001G2101 from Novartis Clinical Trials Website
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Sorafenib
mesh term: Spartalizumab
sharing ipd: No