<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/NCT03810742</url>
  </required_header>
  <id_info>
    <org_study_id>PEP0210</org_study_id>
    <nct_id>NCT03810742</nct_id>
  </id_info>
  <brief_title>Nanoliposomal Irinotecan (Nal-IRI, ONIVYDE®) in Combination With TAS-102 (LONSURF®) in Refractory Solid Tumors</brief_title>
  <official_title>Phase 1 Study of Nanoliposomal Irinotecan (Nal-IRI, ONIVYDE®) in Combination With TAS-102 (LONSURF®) in Refractory Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PharmaEngine</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>PharmaEngine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study is to explore the combination of nal-IRI and TAS-102, which is expected to be an&#xD;
      effective regimen that could be applied to various cancers&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objectives&#xD;
&#xD;
        -  to determine the maximum tolerated dose (MTD) of nal-IRI (ONIVYDE®) in combination with&#xD;
           TAS-102 (LONSURF®)&#xD;
&#xD;
        -  to evaluate the toxicity profile of the combination therapy Secondary Objectives&#xD;
&#xD;
        -  to evaluate the preliminary efficacy of the combination therapy of nal-IRI (ONIVYDE®)&#xD;
           and TAS-102 (LONSURF®)&#xD;
&#xD;
        -  to study the pharmacokinetics of the combination therapy&#xD;
&#xD;
      A phase 1 study with a classical 3 + 3 dose escalation design. The target population is&#xD;
      patients who have pathologically confirmed malignant solid tumors with no standard treatment&#xD;
      available.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 5, 2019</start_date>
  <completion_date type="Anticipated">August 31, 2023</completion_date>
  <primary_completion_date type="Actual">April 30, 2022</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>Determination of Dose Limiting Toxicities (DLT)</measure>
    <time_frame>12 months</time_frame>
    <description>to find the Dose Limiting Toxicity (DLT) of nal-IRI (ONIVYDE®) in combination with TAS-102 (LONSURF®)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evaluation of Safety profile of nal-IRI and TAS-102 - Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>12 months</time_frame>
    <description>Incidence of Treatment-Emergent Adverse Events [Safety] of nal-IRI (ONIVYDE®) in combination with TAS-102 (LONSURF®) according to NCI-CTCAE version 5.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluation of objective tumor response as per Response Evaluation Criteria in Solid Tumors (RECIST)</measure>
    <time_frame>24 months</time_frame>
    <description>the objective tumor rate by using RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics study - (Cmax)</measure>
    <time_frame>6 months</time_frame>
    <description>Concentration of Peak Plasma (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics study - (Tmax)</measure>
    <time_frame>6 months</time_frame>
    <description>maximum concentration of the time taken to reach the (Tmax).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics study - (T1/2)</measure>
    <time_frame>6 months</time_frame>
    <description>time of C max to drop in half taken (T1/2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics study - (AUC0→t)</measure>
    <time_frame>6 months</time_frame>
    <description>area of the plasma concentration versus time curve (AUC0→t).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics study - (AUC0→∞)</measure>
    <time_frame>6 months</time_frame>
    <description>area of the plasma concentration versus under curve (AUC0→∞)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics study - (CL)</measure>
    <time_frame>6 months</time_frame>
    <description>rate of clearance (CL)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Refractory Solid Tumors</condition>
  <arm_group>
    <arm_group_label>Nanoliposomal Irinotecan + TAS-102</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>different dosage combination by Nanoliposomal Irinotecan (nal-IRI, ONIVYDE®) in Combination with TAS-102 (LONSURF®)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nanoliposomal Irinotecan</intervention_name>
    <description>Nanoliposomal Irinotecan (nal-IRI, ONIVYDE®) in Combination with TAS-102 (LONSURF®)</description>
    <arm_group_label>Nanoliposomal Irinotecan + TAS-102</arm_group_label>
    <other_name>TAS-102</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ages between 20 to 70 years old&#xD;
&#xD;
          2. Histologically or cytologically confirmed malignant solid tumors which are advanced or&#xD;
             metastatic, have failed standard treatment or have no standard treatment currently&#xD;
             available&#xD;
&#xD;
          3. ECOG performance status 0 or 1&#xD;
&#xD;
          4. Normal ECG or ECG without any clinically significant findings&#xD;
&#xD;
          5. Adequate hematologic parameters, and hepatic and renal function i. White blood cell&#xD;
             (WBC) count 3000/μL and absolute neutrophil count (ANC) 1500/μL ii. Platelet counts&#xD;
             100,000/μL without platelet transfusion within 14 days iii. Hemoglobin level 10 g/dL&#xD;
             iv. Serum total bilirubin- within normal range v. Serum albumin 3.0 g/dL vi. Serum&#xD;
             alanine aminotransferase (ALT) 3 x the upper limit of normal (ULN) vii. Serum&#xD;
             creatinine 1.5 x ULN&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Received prior nal-IRI (ONIVYDE®) or TAS-102 (LONSURF®) therapy&#xD;
&#xD;
          2. Known hypersensitivity to any of the components of nal-IRI, other liposomal products,&#xD;
             fluoropyrimidines or leucovorin&#xD;
&#xD;
          3. Have liver cirrhosis with Child-Pugh B or Child-Pugh C&#xD;
&#xD;
          4. With active CNS metastasis (indicated by clinical symptoms, cerebral edema, steroid&#xD;
             requirement, or progressive growth)&#xD;
&#xD;
          5. With clinically significant gastrointestinal disorder including hepatic disorders,&#xD;
             bleeding, inflammation, occlusion, or diarrhea &gt; grade 1&#xD;
&#xD;
          6. Life expectancy of less than 3 months&#xD;
&#xD;
          7. Use any anti-cancer or investigational product within 14 days prior to the first date&#xD;
             of study dosing&#xD;
&#xD;
          8. History of any second malignancy in the latest 5 years except curatively treated&#xD;
             non-melanoma skin cancer or treated cervical carcinoma in situ&#xD;
&#xD;
          9. Uncontrolled inter-current illness including, but not limited to, ongoing or active&#xD;
             infection requiring antibiotic treatment, symptomatic congestive heart failure,&#xD;
             unstable angina pectoris, or cardiac arrhythmia, and psychiatric illness or social&#xD;
             situation that would preclude study compliance&#xD;
&#xD;
         10. Homozygous for the UGT1A1 28 allele (TA7/TA7), homozygous for UGT1A1 6 allele (A/A),&#xD;
             or double heterozygous for both UGT1A1 28 allele (TA6/TA7) and UGT1A1 6 allele (G/A)&#xD;
             (only for dose-finding phase)&#xD;
&#xD;
         11. Pregnant or breastfeeding women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chia-Chi Lin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital, Taipei, Taiwan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital</name>
      <address>
        <city>Tainan</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 21, 2018</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>July 17, 2023</last_update_submitted>
  <last_update_submitted_qc>July 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2023</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>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irinotecan</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/NCT03810742
org study id: PEP0210
nct id: NCT03810742
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The study is to explore the combination of nal-IRI and TAS-102, which is expected to be an
      effective regimen that could be applied to various cancers
Primary Objectives

        -  to determine the maximum tolerated dose (MTD) of nal-IRI (ONIVYDE®) in combination with
           TAS-102 (LONSURF®)

        -  to evaluate the toxicity profile of the combination therapy Secondary Objectives

        -  to evaluate the preliminary efficacy of the combination therapy of nal-IRI (ONIVYDE®)
           and TAS-102 (LONSURF®)

        -  to study the pharmacokinetics of the combination therapy

      A phase 1 study with a classical 3 + 3 dose escalation design. The target population is
      patients who have pathologically confirmed malignant solid tumors with no standard treatment
      available.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Determination of Dose Limiting Toxicities (DLT)
time frame: 12 months
description: to find the Dose Limiting Toxicity (DLT) of nal-IRI (ONIVYDE®) in combination with TAS-102 (LONSURF®)
measure: Evaluation of Safety profile of nal-IRI and TAS-102 - Incidence of Treatment-Emergent Adverse Events
time frame: 12 months
description: Incidence of Treatment-Emergent Adverse Events [Safety] of nal-IRI (ONIVYDE®) in combination with TAS-102 (LONSURF®) according to NCI-CTCAE version 5.0
measure: Evaluation of objective tumor response as per Response Evaluation Criteria in Solid Tumors (RECIST)
time frame: 24 months
description: the objective tumor rate by using RECIST v1.1
measure: Pharmacokinetics study - (Cmax)
time frame: 6 months
description: Concentration of Peak Plasma (Cmax)
measure: Pharmacokinetics study - (Tmax)
time frame: 6 months
description: maximum concentration of the time taken to reach the (Tmax).
measure: Pharmacokinetics study - (T1/2)
time frame: 6 months
description: time of C max to drop in half taken (T1/2)
measure: Pharmacokinetics study - (AUC0→t)
time frame: 6 months
description: area of the plasma concentration versus time curve (AUC0→t).
measure: Pharmacokinetics study - (AUC0→∞)
time frame: 6 months
description: area of the plasma concentration versus under curve (AUC0→∞)
measure: Pharmacokinetics study - (CL)
time frame: 6 months
description: rate of clearance (CL)
arm group label: Nanoliposomal Irinotecan + TAS-102
arm group type: Experimental
description: different dosage combination by Nanoliposomal Irinotecan (nal-IRI, ONIVYDE®) in Combination with TAS-102 (LONSURF®)
intervention type: Drug
intervention name: Nanoliposomal Irinotecan
description: Nanoliposomal Irinotecan (nal-IRI, ONIVYDE®) in Combination with TAS-102 (LONSURF®)
arm group label: Nanoliposomal Irinotecan + TAS-102
other name: TAS-102
criteria: 
gender: All
minimum age: 20 Years
maximum age: 70 Years
healthy volunteers: No
last name: Chia-Chi Lin, MD
role: Principal Investigator
affiliation: National Taiwan University Hospital, Taipei, Taiwan
facility: 
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Irinotecan
sharing ipd: No