<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/NCT03008512</url>
  </required_header>
  <id_info>
    <org_study_id>weGePM-HCC</org_study_id>
    <nct_id>NCT03008512</nct_id>
  </id_info>
  <brief_title>A Phase II Study of Weekly Genexol-PM in Patients With Hepatocelluar Carcinoma After Failure of Sorafenib</brief_title>
  <official_title>A Phase II Study of Weekly Genexol-PM in Patients With Advanced Hepatocelluar Carcinoma After Failure of Sorafenib</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gachon University Gil Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gachon University Gil Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluate activity and safety profile of weekly Genexol-PM in patients with&#xD;
      advanced hepatocellular carcinoma for whom sorafenib treatment failed. Patients will receive&#xD;
      Genexol-PM on days 1, 8, and 15 every 4 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hepatocelluar carcinoma (HCC) is a highly vascular neoplasm characterized by arterial&#xD;
      enhancement on CT or MRI. Angiogenesis provides a target for novel prognostic and therapeutic&#xD;
      approaches to HCC. Sorafenib is the standard 1st-line therapy shown to significantly improve&#xD;
      overall survival in advanced HCC. However, sorafenib benefits are mostly transient and&#xD;
      modest. In addition, sorafenib is associated with major toxicities, and about 30% of patients&#xD;
      stop it because of intolerance. Effective therapies are needed for patients who experience&#xD;
      progression during or after receiving sorafenib or who have sorafenib intolerance. Paclitaxel&#xD;
      has an antiagiogenic activity and weekly administration of paclitaxel is considered to have&#xD;
      enhanced efficacy over 3-weekly administration due to greater drug exposure or a direct&#xD;
      antiangiogenic effect. A previous phase I study showed that weekly paclitaxel has activity in&#xD;
      hepatocellular carcinoma and further investigation in phase II trials is warranted.&#xD;
      Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, is believed to be&#xD;
      superior to conventional paclitaxel in terms of the obviation of premedication and the&#xD;
      delivery of higher paclitaxel doses without additional toxicity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Poor accrual&#xD;
  </why_stopped>
  <start_date type="Actual">October 2016</start_date>
  <completion_date type="Actual">February 2021</completion_date>
  <primary_completion_date type="Actual">February 2021</primary_completion_date>
  <phase>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>Progression-free survival rate at 6 months</measure>
    <time_frame>Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Baseline to Death from Any Cause (Approximately 12 Months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>Baseline to Objective Progression (Approximately 12 Months)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Cycle 1 through Follow Up (Approximately 12 Months)</time_frame>
    <description>NCI-CTCAE V4.03</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Carcinoma, Hepatocellular</condition>
  <arm_group>
    <arm_group_label>Genexol-PM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Genexol-PM 100 mg/m2 intravenously for 1 hour on days 1, 8, and 15 of a 28-day cycle up to 8 cycles. Patients will receive study treatment until disease progression, unacceptable toxicity, or withdrawal of consent.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Genexol-PM</intervention_name>
    <arm_group_label>Genexol-PM</arm_group_label>
    <other_name>Cremophor-free, polymeric micelle-formulated paclitaxel</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. A diagnosis of hepatocellular carcinoma (HCC) based on either&#xD;
&#xD;
               1. histopathologic or cytologic findings&#xD;
&#xD;
               2. a diagnosis of cirrhosis and HCC with classical imaging characteristics (at least&#xD;
                  a 3-phase liver protocol CT or MRI and a lesion that demonstrates arterial&#xD;
                  enhancement and washes out in the venous phase)&#xD;
&#xD;
          2. Previous sorafenib treatment for at least 14 days and discontinuation of sorafenib&#xD;
             treatment prior to inclusion&#xD;
&#xD;
          3. Radiologic confirmation of disease progression during or after discontinuation of&#xD;
             sorafenib treatment or discontinuation of sorafenib due to intolerance despite&#xD;
             appropriate supportive care&#xD;
&#xD;
          4. Barcelona Clinic Liver Cancer (BCLC) stage C or BCLC stage B disease not amenable to&#xD;
             locoregional therapy or refractory to locoregional therapy&#xD;
&#xD;
          5. ≥ 1 measurable lesion according to RECIST Version 1.1&#xD;
&#xD;
          6. ≥ 20 year of age&#xD;
&#xD;
          7. ECOG performance status ≤ 2&#xD;
&#xD;
          8. Child-Pugh score ≤ 7&#xD;
&#xD;
          9. Informed consent prior to study&#xD;
&#xD;
         10. Adequate organ function&#xD;
&#xD;
               1. Hepatic: bilirubin ≤ 1.5 times upper limit of institutional normal value (ULN),&#xD;
                  AST or ALT ≤ 5 x ULN&#xD;
&#xD;
               2. Renal: estimated creatinine clearance ≥ 60 mL/min&#xD;
&#xD;
               3. Hematologic: hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1,500/μL,&#xD;
                  platelets ≥ 75,000/μL (In case of thrombocytopenia associated with hypersplenism&#xD;
                  in chronic liver disease, platelets ≥ 50,000/μL is allowed for participation at&#xD;
                  the physician's discretion.)&#xD;
&#xD;
               4. Coagulation: prothrombin time (INR) ≤ 1.5, partial thrombin time (PTT) ≤ 5&#xD;
                  seconds above the ULN&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous systemic chemotherapy for advanced disease (except previous biologic agents&#xD;
             including VEGF inhibitors, TGF-beta inhibitors, or PD-1/PD-L1 blockers)&#xD;
&#xD;
          2. A history o f or current hepatic encephalopathy or clinically meaningful ascites&#xD;
&#xD;
          3. Grade 2 or more peripheral neuropathy&#xD;
&#xD;
          4. Prior liver transplant&#xD;
&#xD;
          5. History of any other cancer within 2 years (Patients with carcinoma in situ of any&#xD;
             origin and patients with prior malignancy who are in remission and whose likelihood of&#xD;
             recurrence is very low, may be eligible.)&#xD;
&#xD;
          6. A history of treatment with taxanes (paclitaxel or docetaxel)&#xD;
&#xD;
          7. Females who are pregnant or lactating&#xD;
&#xD;
          8. A know allergy or hypersensitivity reaction to any of the treatment components&#xD;
&#xD;
          9. Serious preexisting medical conditions that cannot adequately controlled with&#xD;
             appropriate therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dong Bok Shin, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Gachon University Gil Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Gachon University Gil Medical Center</name>
      <address>
        <city>Incheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>Kim TY, Kim DW, Chung JY, Shin SG, Kim SC, Heo DS, Kim NK, Bang YJ. Phase I and pharmacokinetic study of Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin Cancer Res. 2004 Jun 1;10(11):3708-16. doi: 10.1158/1078-0432.CCR-03-0655.</citation>
    <PMID>15173077</PMID>
  </reference>
  <reference>
    <citation>Strumberg D, Erhard J, Harstrick A, Klaassen U, Muller C, Eberhardt W, Wilke H, Seeber S. Phase I study of a weekly 1 h infusion of paclitaxel in patients with unresectable hepatocellular carcinoma. Eur J Cancer. 1998 Jul;34(8):1290-2. doi: 10.1016/s0959-8049(98)00054-9.</citation>
    <PMID>9849493</PMID>
  </reference>
  <reference>
    <citation>Bocci G, Di Paolo A, Danesi R. The pharmacological bases of the antiangiogenic activity of paclitaxel. Angiogenesis. 2013 Jul;16(3):481-92. doi: 10.1007/s10456-013-9334-0. Epub 2013 Feb 7.</citation>
    <PMID>23389639</PMID>
  </reference>
  <reference>
    <citation>Baird RD, Tan DS, Kaye SB. Weekly paclitaxel in the treatment of recurrent ovarian cancer. Nat Rev Clin Oncol. 2010 Oct;7(10):575-82. doi: 10.1038/nrclinonc.2010.120. Epub 2010 Aug 3.</citation>
    <PMID>20683437</PMID>
  </reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>December 29, 2016</study_first_submitted>
  <study_first_submitted_qc>December 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <last_update_submitted>February 2, 2021</last_update_submitted>
  <last_update_submitted_qc>February 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Gachon University Gil Medical Center</investigator_affiliation>
    <investigator_full_name>Young Saing Kim</investigator_full_name>
    <investigator_title>Assistant professor</investigator_title>
  </responsible_party>
  <keyword>Liver Neoplasms</keyword>
  <keyword>Antineoplastic Agents</keyword>
  <keyword>Carcinoma, Hepatocellular</keyword>
  <keyword>Genexol-PM</keyword>
  <keyword>Neoplasms by Site</keyword>
  <keyword>Sorafenib</keyword>
  <keyword>Liver Diseases</keyword>
  <keyword>Digestive System Neoplasms</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>Paclitaxel</mesh_term>
    <mesh_term>genexol-PM</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/NCT03008512
org study id: weGePM-HCC
nct id: NCT03008512
lead sponsor: 
has dmc: Yes
This study evaluate activity and safety profile of weekly Genexol-PM in patients with
      advanced hepatocellular carcinoma for whom sorafenib treatment failed. Patients will receive
      Genexol-PM on days 1, 8, and 15 every 4 weeks.
Hepatocelluar carcinoma (HCC) is a highly vascular neoplasm characterized by arterial
      enhancement on CT or MRI. Angiogenesis provides a target for novel prognostic and therapeutic
      approaches to HCC. Sorafenib is the standard 1st-line therapy shown to significantly improve
      overall survival in advanced HCC. However, sorafenib benefits are mostly transient and
      modest. In addition, sorafenib is associated with major toxicities, and about 30% of patients
      stop it because of intolerance. Effective therapies are needed for patients who experience
      progression during or after receiving sorafenib or who have sorafenib intolerance. Paclitaxel
      has an antiagiogenic activity and weekly administration of paclitaxel is considered to have
      enhanced efficacy over 3-weekly administration due to greater drug exposure or a direct
      antiangiogenic effect. A previous phase I study showed that weekly paclitaxel has activity in
      hepatocellular carcinoma and further investigation in phase II trials is warranted.
      Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, is believed to be
      superior to conventional paclitaxel in terms of the obviation of premedication and the
      delivery of higher paclitaxel doses without additional toxicity.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival rate at 6 months
time frame: Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months)
measure: Progression-free survival
time frame: Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months)
measure: Overall survival
time frame: Baseline to Death from Any Cause (Approximately 12 Months)
measure: Objective response rate
time frame: Baseline to Objective Progression (Approximately 12 Months)
measure: Adverse events
time frame: Cycle 1 through Follow Up (Approximately 12 Months)
description: NCI-CTCAE V4.03
arm group label: Genexol-PM
arm group type: Experimental
description: Genexol-PM 100 mg/m2 intravenously for 1 hour on days 1, 8, and 15 of a 28-day cycle up to 8 cycles. Patients will receive study treatment until disease progression, unacceptable toxicity, or withdrawal of consent.
intervention type: Drug
intervention name: Genexol-PM
arm group label: Genexol-PM
other name: Cremophor-free, polymeric micelle-formulated paclitaxel
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Dong Bok Shin, Professor
role: Principal Investigator
affiliation: Gachon University Gil Medical Center
facility: 
facility: 
country: Korea, Republic of
citation: Kim TY, Kim DW, Chung JY, Shin SG, Kim SC, Heo DS, Kim NK, Bang YJ. Phase I and pharmacokinetic study of Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin Cancer Res. 2004 Jun 1;10(11):3708-16. doi: 10.1158/1078-0432.CCR-03-0655.
PMID: 15173077
citation: Strumberg D, Erhard J, Harstrick A, Klaassen U, Muller C, Eberhardt W, Wilke H, Seeber S. Phase I study of a weekly 1 h infusion of paclitaxel in patients with unresectable hepatocellular carcinoma. Eur J Cancer. 1998 Jul;34(8):1290-2. doi: 10.1016/s0959-8049(98)00054-9.
PMID: 9849493
citation: Bocci G, Di Paolo A, Danesi R. The pharmacological bases of the antiangiogenic activity of paclitaxel. Angiogenesis. 2013 Jul;16(3):481-92. doi: 10.1007/s10456-013-9334-0. Epub 2013 Feb 7.
PMID: 23389639
citation: Baird RD, Tan DS, Kaye SB. Weekly paclitaxel in the treatment of recurrent ovarian cancer. Nat Rev Clin Oncol. 2010 Oct;7(10):575-82. doi: 10.1038/nrclinonc.2010.120. Epub 2010 Aug 3.
PMID: 20683437
responsible party type: Principal Investigator
investigator affiliation: Gachon University Gil Medical Center
investigator full name: Young Saing Kim
investigator title: Assistant professor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Paclitaxel
mesh term: genexol-PM
sharing ipd: Undecided