<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/NCT03035006</url>
  </required_header>
  <id_info>
    <org_study_id>TLC388A1008</org_study_id>
    <nct_id>NCT03035006</nct_id>
  </id_info>
  <brief_title>Lipotecan Based Concurrent Chemoradiotherapy in Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis</brief_title>
  <official_title>A Phase I/II, Dose-escalation Study of Lipotecan Based Concurrent Chemoradiotherapy in Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Taiwan Liposome Company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Taiwan Liposome Company</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase I/II dose-escalation study of lipotecan based concurrent chemoradiotherapy in&#xD;
      hepatocellular carcinoma with portal vein tumor thrombosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Protocol number: TLCTLC388A1008&#xD;
&#xD;
      Primary objective:&#xD;
&#xD;
      To evaluate the safety and tolerability, including maximum tolerated dose (MTD) and&#xD;
      dose-limiting toxicity (DLT), of Lipotecan based concurrent chemoradiotherapy (CCRT) in&#xD;
      patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT)&#xD;
      unsuitable for local treatment.&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
      The secondary objective is to explore the efficacy of Lipotecan based CCRT in patients with&#xD;
      HCC and PVTT and the effect on quality of life.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Current study design couldn't support futher development on this indication.&#xD;
  </why_stopped>
  <start_date type="Actual">April 14, 2017</start_date>
  <completion_date type="Actual">October 31, 2018</completion_date>
  <primary_completion_date type="Actual">October 31, 2018</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>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose determination for Lipotecan based CCRT</measure>
    <time_frame>3 months</time_frame>
    <description>To determine maximum tolerated dose for Lipotecan based CCRT in HCC patients with portal vein tumor thrombosis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Best objective response evaluation of portal vein tumor thrombosis</measure>
    <time_frame>1 year</time_frame>
    <description>To evaluate the best objective response rate of portal vein tumor thrombosis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Conversion rate (CR) of portal vein tumor thrombosis</measure>
    <time_frame>1 year</time_frame>
    <description>To evaluate the conversion rate (CR rate) of PVTT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best overall response of overall disease</measure>
    <time_frame>1 year</time_frame>
    <description>To evaluate the best overall response rate of overall disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate of portal vein tumor thrombosis, liver tumors and overall disease</measure>
    <time_frame>1 year</time_frame>
    <description>To evaluate DCR of PVTT, liver tumors (target lesions), and overall disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression of overall disease</measure>
    <time_frame>1 year</time_frame>
    <description>To evaluate the TTP of overall disease after the start of concomitant Lipotecan based CCRT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival of overall disease</measure>
    <time_frame>1 year</time_frame>
    <description>To evaluate the PFS of overall disease after the start of concomitant Lipotecan based CCRT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival of overall disease</measure>
    <time_frame>1 year</time_frame>
    <description>To evaluate the OS after the start of concomitant Lipotecan based CCRT</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>HepatoCellular Carcinoma</condition>
  <condition>Portal Vein Tumor Thrombosis</condition>
  <arm_group>
    <arm_group_label>Lipotecan based chemoradiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive Lipotecan based CCRT. Lipotecan will be given as a 30-minute (±3 minutes) iv infusion qw for 6 weeks at the predefined dose level for each cohort. A total of 6 doses of Lipotecan will be administered to each patient in conjunction with RT at 3.5 Gy per fraction for 16 fractions. During CCRT period, Lipotecan should be given within 2 hours prior to the start of RT, and the Lipotecan and RT should be delivered on the same day, unless any conditions fulfils with the dose interruption standards. Radiotherapy treatment, at the allocated dose level, is only permitted if the normal tissue dose constrain criteria are maintained</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lipotecan</intervention_name>
    <description>Lipotecan based concurrent chemoradiotherapy</description>
    <arm_group_label>Lipotecan based chemoradiotherapy</arm_group_label>
    <other_name>TLC388</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients will be males or females&#xD;
&#xD;
               -  ≥20 years of age in Taiwan&#xD;
&#xD;
               -  ≥18 years old in China&#xD;
&#xD;
          2. Patients with histologically confirmed HCC or patients who do not have histological&#xD;
             diagnosis, but the lesion is larger than 1 cm in a cirrhotic liver with typical HCC&#xD;
             image of contrast enhanced CT scan or MRI. If the image characteristic is not typical&#xD;
             of HCC, another contrast enhanced image modality should be confirmed for diagnosis.&#xD;
&#xD;
          3. Patients with PVTT (BCLC stage C) who are not suitable for local therapies&#xD;
&#xD;
          4. Patients with a measureable targeting lesion&#xD;
&#xD;
          5. Patients with an anticipated residual life expectancy ≥3 months&#xD;
&#xD;
          6. Patients who have adequate organ function&#xD;
&#xD;
          7. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2&#xD;
&#xD;
          8. Patients who are willing to follow birth control requirements during the study&#xD;
             treatment and continue until 2 months after the completion of study treatment&#xD;
&#xD;
          9. Patients willing and able to comply with the study procedures and to sign a written&#xD;
             ICF&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with infiltrative type HCC&#xD;
&#xD;
          2. Patients with evidence of any extrahepatic metastasis, including but not limited to&#xD;
             inferior vena cava thrombosis, bone metastasis, brain metastasis, or regional lymph&#xD;
             node metastasis&#xD;
&#xD;
          3. Patients with a history of West Haven criteria grade III-IV hepatic encephalopathy or&#xD;
             ascites&#xD;
&#xD;
          4. Patients with a history of other malignancy except primary HCC within 3 years prior to&#xD;
             the screening visit, excluding skin squamous cell carcinoma or basal cell carcinoma&#xD;
&#xD;
          5. Patients who fail to follow the radiation dose constraint in any critical organ in the&#xD;
             radiotherapy planning&#xD;
&#xD;
          6. Patients with an inadequately defined hepatic tumor margin for RT planning on MRI or&#xD;
             CT that may impact treatment or safety based on investigator's judgment&#xD;
&#xD;
          7. Patients who have experienced significant allergy or hypersensitivity to the contrast&#xD;
             medium for CT or MRI that makes it unsafe to perform the delineation for RT planning&#xD;
&#xD;
          8. Patients with a history of liver transplantation&#xD;
&#xD;
          9. Patients with a significant concurrent 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>Carl Brown, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Taiwan Liposome Company</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taichung Veterans General Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hosipital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veteran General Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>January 25, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 27, 2017</study_first_posted>
  <last_update_submitted>November 4, 2018</last_update_submitted>
  <last_update_submitted_qc>November 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatocellular carcinoma</keyword>
  <keyword>Portal vein tumor thrombosis</keyword>
  <keyword>TLC388</keyword>
  <keyword>Chemoradiotherapy</keyword>
  <keyword>Lipotecan</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>
    <mesh_term>Thrombosis</mesh_term>
  </condition_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/NCT03035006
org study id: TLC388A1008
nct id: NCT03035006
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a phase I/II dose-escalation study of lipotecan based concurrent chemoradiotherapy in
      hepatocellular carcinoma with portal vein tumor thrombosis.
Protocol number: TLCTLC388A1008

      Primary objective:

      To evaluate the safety and tolerability, including maximum tolerated dose (MTD) and
      dose-limiting toxicity (DLT), of Lipotecan based concurrent chemoradiotherapy (CCRT) in
      patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT)
      unsuitable for local treatment.

      Secondary Objective:

      The secondary objective is to explore the efficacy of Lipotecan based CCRT in patients with
      HCC and PVTT and the effect on quality of life.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose determination for Lipotecan based CCRT
time frame: 3 months
description: To determine maximum tolerated dose for Lipotecan based CCRT in HCC patients with portal vein tumor thrombosis
measure: Best objective response evaluation of portal vein tumor thrombosis
time frame: 1 year
description: To evaluate the best objective response rate of portal vein tumor thrombosis
measure: Conversion rate (CR) of portal vein tumor thrombosis
time frame: 1 year
description: To evaluate the conversion rate (CR rate) of PVTT
measure: Best overall response of overall disease
time frame: 1 year
description: To evaluate the best overall response rate of overall disease
measure: Disease control rate of portal vein tumor thrombosis, liver tumors and overall disease
time frame: 1 year
description: To evaluate DCR of PVTT, liver tumors (target lesions), and overall disease
measure: Time to progression of overall disease
time frame: 1 year
description: To evaluate the TTP of overall disease after the start of concomitant Lipotecan based CCRT
measure: Progression free survival of overall disease
time frame: 1 year
description: To evaluate the PFS of overall disease after the start of concomitant Lipotecan based CCRT
measure: Overall survival of overall disease
time frame: 1 year
description: To evaluate the OS after the start of concomitant Lipotecan based CCRT
arm group label: Lipotecan based chemoradiotherapy
arm group type: Experimental
description: Patients will receive Lipotecan based CCRT. Lipotecan will be given as a 30-minute (±3 minutes) iv infusion qw for 6 weeks at the predefined dose level for each cohort. A total of 6 doses of Lipotecan will be administered to each patient in conjunction with RT at 3.5 Gy per fraction for 16 fractions. During CCRT period, Lipotecan should be given within 2 hours prior to the start of RT, and the Lipotecan and RT should be delivered on the same day, unless any conditions fulfils with the dose interruption standards. Radiotherapy treatment, at the allocated dose level, is only permitted if the normal tissue dose constrain criteria are maintained
intervention type: Drug
intervention name: Lipotecan
description: Lipotecan based concurrent chemoradiotherapy
arm group label: Lipotecan based chemoradiotherapy
other name: TLC388
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Carl Brown, PhD
role: Study Director
affiliation: Taiwan Liposome Company
facility: 
facility: 
facility: 
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Thrombosis
sharing ipd: Undecided