<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/NCT02240771</url>
  </required_header>
  <id_info>
    <org_study_id>TAC-HCC</org_study_id>
    <nct_id>NCT02240771</nct_id>
  </id_info>
  <brief_title>Transarterial Chemotherapy Compared With Oral Chemotherapy in the Treatment of Advanced Hepatocellular Carcinoma</brief_title>
  <official_title>Randomized Control Trial of Transarterial Chemotherapy (TAC) Versus Oral Thalidomide and Capecitabine in the Treatment of Unresectable Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>All India Institute of Medical Sciences, New Delhi</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Indian Council of Medical Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>All India Institute of Medical Sciences, New Delhi</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In India, majority of our patients have advanced hepatocellular carcinoma (HCC) at&#xD;
      presentation and hence are unsuitable for the available curative treatment options. In such&#xD;
      patients the treatment options are mainly palliative. Transarterial chemoembolization (TACE),&#xD;
      transarterial chemotherapy (TAC) and various forms of oral chemotherapy are the only&#xD;
      available options currently. Many patients have more advanced disease with the involvement of&#xD;
      branches of portal vein. This further limits the therapeutic options. According to Barcelona&#xD;
      Clinic Liver Cancer (BCLC) staging, involvement of portal vein precludes any standard form of&#xD;
      therapy. TAC and oral chemotherapy has been tried in this group of patients by few&#xD;
      researchers. Which treatment (TAC or oral chemotherapy) would be better suitable for advanced&#xD;
      stage (BCLC C) needs to be explored. However, there are no randomized controlled trials&#xD;
      (RCT's) available.&#xD;
&#xD;
      TAC is the procedure for treating patients of HCC with portal vein invasion where only the&#xD;
      chemotherapeutic drugs are injected into the feeding vessels of the tumor with no subsequent&#xD;
      embolization of the feeding vessels.&#xD;
&#xD;
      In order to select a modality which would produce better outcomes in advanced HCC patients&#xD;
      (BCLC C), this study was planned.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Aim of the study: To see the efficacy of transarterial chemotherapy in prolonging the&#xD;
      survival of patients with unresectable HCC when compared to oral chemotherapy 2. Diagnostic&#xD;
      criteria&#xD;
&#xD;
      o Cirrhosis of liver- Diagnosis will be founded on the basis of clinical, biochemical,&#xD;
      imaging and endoscopy findings.&#xD;
&#xD;
      o Hepatocellular carcinoma- when any one of the following is present&#xD;
&#xD;
        1. Two imaging modalities (dual phase CT (DPCT)/ contrast enhanced MRI) showing&#xD;
           arterialization of the hepatic mass&#xD;
&#xD;
        2. Alpha feto protein (AFP) more than 400ng/ml along with arterialization on one imaging&#xD;
           modality (DPCT/ contrast enhanced MRI)&#xD;
&#xD;
        3. Fine-needle aspiration cytology (FNAC)&#xD;
&#xD;
      3. Definitions&#xD;
&#xD;
      3.1. Unresectable HCC- • Liver mass larger than 5cm in diameter (single/ multiple) ,&#xD;
      involving main portal vein with underlying cirrhotic liver&#xD;
&#xD;
      3.2. Tumor response This will be based on Dual phase CT findings&#xD;
&#xD;
        -  Complete response (CR)- Tumor fully covered with lipiodol showing no viable tissue&#xD;
&#xD;
        -  Partial response (PR)- Tumor partially covered (&gt;75%) by lipiodol&#xD;
&#xD;
        -  Mild response (MR)- About 50 to 75% coverage of the tumor by lipiodol&#xD;
&#xD;
        -  No response (NR) - About 25 to 50% coverage of the tumor by lipiodol&#xD;
&#xD;
        -  Fresh lesions (FL)- Appearance of new mass lesions in the liver with or without&#xD;
           recurrence at the site of previous mass&#xD;
&#xD;
      3.3 Patient tolerance Grade 1: no side effects Grade 2: moderate side effects Grade 3: severe&#xD;
      side effects Grade 4: life threatening side effects&#xD;
&#xD;
      3.4 Performance status (PST score) PST score of 0-5 would be assessed on the following basis&#xD;
      0- No cancer related symptoms. Normal life style&#xD;
&#xD;
        1. Minor symptoms related to cancer. Capable of non-strenuous activity. Fully ambulatory&#xD;
&#xD;
        2. Ambulatory and capable of all self-care but unable to carry out any work activities.&#xD;
           Confined to bed less than 50% of waking hours&#xD;
&#xD;
        3. Capable of only limited self-care. Confined to bed more than 50% of waking hours.&#xD;
&#xD;
        4. Completely disabled. Cannot carry on any self-care. Totally confined to bed.&#xD;
&#xD;
        5. Death&#xD;
&#xD;
      4. Sample Size Systematic review of RCT's for TAC show a 2-year survival of 40 %. Expecting&#xD;
      that oral chemotherapy has a 2-year survival of 40% with 5% non-inferiority margin with 80%&#xD;
      power and 5% error, a sample size of 124 patients in each arm would be required.(Total 248&#xD;
      patients)&#xD;
&#xD;
      5. Randomization&#xD;
&#xD;
      • Patients will be randomized after the confirmation of diagnosis and obtaining written&#xD;
      consent&#xD;
&#xD;
        -  Sequences will be generated by the Statistician&#xD;
&#xD;
        -  Stratified randomization will be done. Two strata of child's A and B will be made&#xD;
&#xD;
        -  Randomization will be done by drawing consecutively numbered opaque sealed envelopes&#xD;
           Randomization into A (TAC) and B (oral chemotherapy) will be done&#xD;
&#xD;
           6. Follow up post TAC&#xD;
&#xD;
      6.1 Clinical follow up&#xD;
&#xD;
        -  All patients would be followed up in the Liver clinic monthly unless their clinical&#xD;
           condition warrants earlier follow up&#xD;
&#xD;
        -  Liver function tests/ complete blood count would also be done at each visit and AFP (if&#xD;
           elevated earlier) every six months&#xD;
&#xD;
        -  Patient tolerance, child's status would be estimated.&#xD;
&#xD;
      6.2 Imaging follow up&#xD;
&#xD;
        -  At one month, a dual phase CT would be done to ascertain the response to therapy and the&#xD;
           need to repeat the procedure. Subsequently, the DPCT would be done at 3 and 6 monthly&#xD;
           intervals.&#xD;
&#xD;
           7. Repeat TAC on follow up This would be done if any of the following is noted&#xD;
&#xD;
        -  DPCT shows viable tumor&#xD;
&#xD;
        -  Fresh lesions appear&#xD;
&#xD;
        -  Elevated serum AFP occurs with or without appearance of viable mass on DPCT&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2006</start_date>
  <completion_date type="Anticipated">March 2015</completion_date>
  <primary_completion_date type="Anticipated">December 2014</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Survival rate-</measure>
    <time_frame>1 year</time_frame>
    <description>Survival rate to be calculated from the start of Transarterial chemotherapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor response</measure>
    <time_frame>1 year</time_frame>
    <description>Tumor response on dual phase contrast-enhanced computed tomography (CECT)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">124</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Transarterial chemotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Doxorubicin 50mg, Cisplatin 100mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral chemotherapy</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Thalidomide---50-300mg once a day Capecitabine---- 500-1500mg once a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Transarterial chemotherapy</intervention_name>
    <description>Femoral artery would be punctured at the upper thigh using 18 gauge needle under local anesthesia. Catheterization of the hepatic artery feeding the tumor would be done and placing the catheter tip beyond the gastroduodenal artery, the chemotherapeutic drugs would be administered.&#xD;
Mixture would be prepared by using Doxorubicin 50mg and Cisplatin 100mg. Hydrocortisone 100mg and augmenting dose of analgesic and sedative would be injected prior to the administration of the drug.&#xD;
The drug mixture would then be injected through the indwelling arterial catheter by continuously flushing alternately, repeatedly and rapidly between two-leur lock syringes.</description>
    <arm_group_label>Transarterial chemotherapy</arm_group_label>
    <other_name>TAC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral chemotherapy</intervention_name>
    <description>Drugs used would be Thalidomide and Capecitabine in the following dosage schedule- Thalidomide---50mg once a day (OD) for 7 days, increased to 100mg OD for 7 days, 200mgOD for 7 days further increased to 300 mg OD.&#xD;
Capecitabine---- 500mg OD for 7 days, then 1000mg OD for next 7 days, increased to a maximum dose of 1500mg OD&#xD;
Maintenance dose - Capecitabine 1500 mg - every alternate week Thalidomide - 300 mg OD. Total leucocyte count &amp; Platelet count would be monitored every 15 days</description>
    <arm_group_label>Oral chemotherapy</arm_group_label>
    <other_name>OC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients above 12 years of age with performance status (PST) score of 0-2&#xD;
&#xD;
          -  Unresectable HCC with underlying Child's A/B cirrhosis&#xD;
&#xD;
          -  Blocked Main portal vein&#xD;
&#xD;
          -  No history of drug allergy&#xD;
&#xD;
          -  Informed written consent of patient.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Child's C cirrhosis&#xD;
&#xD;
          -  Performance status 3-5&#xD;
&#xD;
          -  Extra hepatic disease&#xD;
&#xD;
          -  Co-morbid illness like coronary artery disease, congestive heart failure, chronic&#xD;
             renal failure etc&#xD;
&#xD;
          -  Previous history of encephalopathy/ upper gastrointestinal bleed in the last six&#xD;
             months&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Subrat K Acharya, D.M</last_name>
    <role>Principal Investigator</role>
    <affiliation>All India Institute of Medical Sciences, New Delhi, India</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>AII India Institute of Medical Sciences</name>
      <address>
        <city>New Delhi</city>
        <state>Delhi</state>
        <zip>110029</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Subrat K Acharya, DM</last_name>
      <phone>+91-11-26594934</phone>
      <email>subratacharya2004@yahoo.com</email>
    </contact>
    <contact_backup>
      <last_name>Shalimar . ., DM</last_name>
      <phone>+91-9968405815</phone>
      <email>drshalimar@yahoo.com</email>
    </contact_backup>
    <investigator>
      <last_name>Subrat K Acharya, DM</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Shashi B. Paul, Ph.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Shivanand R Gamanagatti, M.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sreenivas Vishnubhatla, Ph.D</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>August 31, 2014</study_first_submitted>
  <study_first_submitted_qc>September 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <last_update_submitted>September 12, 2014</last_update_submitted>
  <last_update_submitted_qc>September 12, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 16, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>All India Institute of Medical Sciences, New Delhi</investigator_affiliation>
    <investigator_full_name>Subrat Kumar Acharya</investigator_full_name>
    <investigator_title>Professor &amp; Head</investigator_title>
  </responsible_party>
  <keyword>Transarterial chemotherapy</keyword>
  <keyword>Thalidomide</keyword>
  <keyword>Capecitabine</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>
  <!-- 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/NCT02240771
org study id: TAC-HCC
nct id: NCT02240771
lead sponsor: 
collaborator: 
has dmc: Yes
In India, majority of our patients have advanced hepatocellular carcinoma (HCC) at
      presentation and hence are unsuitable for the available curative treatment options. In such
      patients the treatment options are mainly palliative. Transarterial chemoembolization (TACE),
      transarterial chemotherapy (TAC) and various forms of oral chemotherapy are the only
      available options currently. Many patients have more advanced disease with the involvement of
      branches of portal vein. This further limits the therapeutic options. According to Barcelona
      Clinic Liver Cancer (BCLC) staging, involvement of portal vein precludes any standard form of
      therapy. TAC and oral chemotherapy has been tried in this group of patients by few
      researchers. Which treatment (TAC or oral chemotherapy) would be better suitable for advanced
      stage (BCLC C) needs to be explored. However, there are no randomized controlled trials
      (RCT's) available.

      TAC is the procedure for treating patients of HCC with portal vein invasion where only the
      chemotherapeutic drugs are injected into the feeding vessels of the tumor with no subsequent
      embolization of the feeding vessels.

      In order to select a modality which would produce better outcomes in advanced HCC patients
      (BCLC C), this study was planned.
1. Aim of the study: To see the efficacy of transarterial chemotherapy in prolonging the
      survival of patients with unresectable HCC when compared to oral chemotherapy 2. Diagnostic
      criteria

      o Cirrhosis of liver- Diagnosis will be founded on the basis of clinical, biochemical,
      imaging and endoscopy findings.

      o Hepatocellular carcinoma- when any one of the following is present

        1. Two imaging modalities (dual phase CT (DPCT)/ contrast enhanced MRI) showing
           arterialization of the hepatic mass

        2. Alpha feto protein (AFP) more than 400ng/ml along with arterialization on one imaging
           modality (DPCT/ contrast enhanced MRI)

        3. Fine-needle aspiration cytology (FNAC)

      3. Definitions

      3.1. Unresectable HCC- • Liver mass larger than 5cm in diameter (single/ multiple) ,
      involving main portal vein with underlying cirrhotic liver

      3.2. Tumor response This will be based on Dual phase CT findings

        -  Complete response (CR)- Tumor fully covered with lipiodol showing no viable tissue

        -  Partial response (PR)- Tumor partially covered (>75%) by lipiodol

        -  Mild response (MR)- About 50 to 75% coverage of the tumor by lipiodol

        -  No response (NR) - About 25 to 50% coverage of the tumor by lipiodol

        -  Fresh lesions (FL)- Appearance of new mass lesions in the liver with or without
           recurrence at the site of previous mass

      3.3 Patient tolerance Grade 1: no side effects Grade 2: moderate side effects Grade 3: severe
      side effects Grade 4: life threatening side effects

      3.4 Performance status (PST score) PST score of 0-5 would be assessed on the following basis
      0- No cancer related symptoms. Normal life style

        1. Minor symptoms related to cancer. Capable of non-strenuous activity. Fully ambulatory

        2. Ambulatory and capable of all self-care but unable to carry out any work activities.
           Confined to bed less than 50% of waking hours

        3. Capable of only limited self-care. Confined to bed more than 50% of waking hours.

        4. Completely disabled. Cannot carry on any self-care. Totally confined to bed.

        5. Death

      4. Sample Size Systematic review of RCT's for TAC show a 2-year survival of 40 %. Expecting
      that oral chemotherapy has a 2-year survival of 40% with 5% non-inferiority margin with 80%
      power and 5% error, a sample size of 124 patients in each arm would be required.(Total 248
      patients)

      5. Randomization

      • Patients will be randomized after the confirmation of diagnosis and obtaining written
      consent

        -  Sequences will be generated by the Statistician

        -  Stratified randomization will be done. Two strata of child's A and B will be made

        -  Randomization will be done by drawing consecutively numbered opaque sealed envelopes
           Randomization into A (TAC) and B (oral chemotherapy) will be done

           6. Follow up post TAC

      6.1 Clinical follow up

        -  All patients would be followed up in the Liver clinic monthly unless their clinical
           condition warrants earlier follow up

        -  Liver function tests/ complete blood count would also be done at each visit and AFP (if
           elevated earlier) every six months

        -  Patient tolerance, child's status would be estimated.

      6.2 Imaging follow up

        -  At one month, a dual phase CT would be done to ascertain the response to therapy and the
           need to repeat the procedure. Subsequently, the DPCT would be done at 3 and 6 monthly
           intervals.

           7. Repeat TAC on follow up This would be done if any of the following is noted

        -  DPCT shows viable tumor

        -  Fresh lesions appear

        -  Elevated serum AFP occurs with or without appearance of viable mass on DPCT
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Survival rate-
time frame: 1 year
description: Survival rate to be calculated from the start of Transarterial chemotherapy
measure: Tumor response
time frame: 1 year
description: Tumor response on dual phase contrast-enhanced computed tomography (CECT)
arm group label: Transarterial chemotherapy
arm group type: Active Comparator
description: Doxorubicin 50mg, Cisplatin 100mg
arm group label: Oral chemotherapy
arm group type: Placebo Comparator
description: Thalidomide---50-300mg once a day Capecitabine---- 500-1500mg once a day
intervention type: Procedure
intervention name: Transarterial chemotherapy
description: Femoral artery would be punctured at the upper thigh using 18 gauge needle under local anesthesia. Catheterization of the hepatic artery feeding the tumor would be done and placing the catheter tip beyond the gastroduodenal artery, the chemotherapeutic drugs would be administered.
Mixture would be prepared by using Doxorubicin 50mg and Cisplatin 100mg. Hydrocortisone 100mg and augmenting dose of analgesic and sedative would be injected prior to the administration of the drug.
The drug mixture would then be injected through the indwelling arterial catheter by continuously flushing alternately, repeatedly and rapidly between two-leur lock syringes.
arm group label: Transarterial chemotherapy
other name: TAC
intervention type: Drug
intervention name: Oral chemotherapy
description: Drugs used would be Thalidomide and Capecitabine in the following dosage schedule- Thalidomide---50mg once a day (OD) for 7 days, increased to 100mg OD for 7 days, 200mgOD for 7 days further increased to 300 mg OD.
Capecitabine---- 500mg OD for 7 days, then 1000mg OD for next 7 days, increased to a maximum dose of 1500mg OD
Maintenance dose - Capecitabine 1500 mg - every alternate week Thalidomide - 300 mg OD. Total leucocyte count & Platelet count would be monitored every 15 days
arm group label: Oral chemotherapy
other name: OC
criteria: 
gender: All
minimum age: 12 Years
maximum age: 80 Years
healthy volunteers: No
last name: Subrat K Acharya, D.M
role: Principal Investigator
affiliation: All India Institute of Medical Sciences, New Delhi, India
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
country: India
responsible party type: Principal Investigator
investigator affiliation: All India Institute of Medical Sciences, New Delhi
investigator full name: Subrat Kumar Acharya
investigator title: Professor & Head
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular