<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/NCT03267641</url>
  </required_header>
  <id_info>
    <org_study_id>AHCC07</org_study_id>
    <nct_id>NCT03267641</nct_id>
  </id_info>
  <brief_title>Prospective Cohort Study on the Clinical Trajectory of Resected Hepatocellular Carcinoma</brief_title>
  <acronym>PLANET</acronym>
  <official_title>A Multi-National Cohort Study On The Impact Of Intra-Tumoural Genomic Heterogeneity And The Immune Micro-Environment On The Clinical Trajectory Of Resected Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Centre, Singapore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Singapore Clinical Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Cancer Centre, Singapore</source>
  <oversight_info>
    <has_dmc>No</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>
      Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world but the 2nd most&#xD;
      important cause of cancer death. Because of its highly heterogeneous nature, the current&#xD;
      approach to identifying druggable targets have not delivered efficacious therapies in HCC and&#xD;
      is a main reason for the high case fatality. Even when surgical resection is potentially&#xD;
      curative in early disease, tumor recurrence remains high and long term survival poor because&#xD;
      of the absence of useful adjuvant therapy.&#xD;
&#xD;
      To address these unmet needs, the investigators bring together internationally recognized&#xD;
      scientists from genomics and immunology and established clinician investigators in a&#xD;
      synergistic team. This TCR capitalizes on recent collaborative advances made by the PIs in&#xD;
      the consortium. The investigators have shown through multi-region sampling of freshly&#xD;
      resected HCC and phylogenetic analysis, that significant intra-tumoral heterogeneity exists&#xD;
      and have identified the specific positions of known clonal drivers. Simultaneously the&#xD;
      investigators have analyzed the immune landscape of the tumor microenvironment with deep&#xD;
      immune-phenotyping and found unique inter-patient immune landscapes predictive of clinical&#xD;
      trajectory.&#xD;
&#xD;
      This TCR is a prospective study that samples resected HCC from multi-ethnic sites within the&#xD;
      established Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group, which has enrolled&#xD;
      approximately 1000 patients through 6 multi-center trials in 35 centers in the region.&#xD;
      Clinical trajectories are tracked and genomic and immunological studies are repeated when&#xD;
      tumors recu r, to confirm clonally dominant driver mutations and immunological processes that&#xD;
      are targetable. Concurrently, representative pre-clinical models will be developed from the&#xD;
      tissues sampled.&#xD;
&#xD;
      The investigators aim to combine these approaches to overcome the challenges posed by genomic&#xD;
      heterogeneity and to guide the development of therapeutics and precision medicine in HCC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 16, 2016</start_date>
  <completion_date type="Actual">March 31, 2021</completion_date>
  <primary_completion_date type="Actual">March 31, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Time to recurrence</measure>
    <time_frame>From date of Complete Response (CR) to first recurrence of HCC, up to 3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease-free Survival</measure>
    <time_frame>From date of CR to first recurrence of HCC or death, due to any cause, up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free Specific Survival</measure>
    <time_frame>From date of CR to first recurrence of HCC or death, due to HCC, up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From diagnosis to date of death due to any cause, up to 3 years</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">86</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Tumour samples Blood samples Urine samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who have undergone resection of HCC with curative intent with a R0 and R1&#xD;
        resection margin&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female patients, 21 to 80 years of age at the time of signature of the&#xD;
             informed consent form.&#xD;
&#xD;
          2. Histologically proven HCC after liver resection. Combined&#xD;
             hepatocellular-cholangiocarcinoma can be included.&#xD;
&#xD;
          3. HCC limited to the liver with no extra-hepatic metastasis on CT or MRI of the abdomen&#xD;
             and chest (defined as lymph node &lt;2 cm, lung nodules &lt; 1 cm, farther lymph nodes &lt; 2&#xD;
             cm) according to the AASLD criteria65.&#xD;
&#xD;
          4. R0 or R1 resection on histology.&#xD;
&#xD;
          5. Eligibility according to tumour size:&#xD;
&#xD;
               1. Large tumour &gt;= 5 cm (preferred)&#xD;
&#xD;
               2. Smaller tumours &gt;=2cm and &lt; 5cm&#xD;
&#xD;
               3. Multifocal tumours - maximum of 3 total tumours with size &gt;=2cm detected from&#xD;
                  CT-scan. Detection of &lt;1cm tumour intra-operatively or upon histologic&#xD;
                  examination following resection can be ignored. For multiple satellite nodules&#xD;
                  (&gt;=2cm) that are detected intraoperatively, harvest ALL satellite nodules (&gt;/=&#xD;
                  2cm). DNA/RNA will be extracted from cases confirmed to be&#xD;
                  HCC/hepato-cholangiocarcinoma by histology. A MAXIMUM of 3 samples with the best&#xD;
                  quality are to be used for the analysis.&#xD;
&#xD;
          6. Child-Pugh ≤ 7 points without clinical ascites before surgery.&#xD;
&#xD;
          7. ECOG performance status 0-1 before surgery.&#xD;
&#xD;
          8. Scheduled for liver resection within 6 weeks.&#xD;
&#xD;
          9. The patient has received no anti-cancer specific treatment for HCC eg. previous liver&#xD;
             resection, loco-regional therapy (e.g. RFA, TACE, SIRT), radiotherapy, immunotherapy,&#xD;
             chemotherapy or neo-adjuvant chemotherapy other than the planned surgery. However,&#xD;
             patient who has received previous HCC resection more than 5 years ago is deemed to&#xD;
             have a de-novo liver tumour and therefore can be included.&#xD;
&#xD;
         10. Adequate bone-marrow reserve, renal function and hepatic function as assessed by&#xD;
             standard laboratory criteria:&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1.0 x 10^9/L&#xD;
&#xD;
               -  Platelet count ≥ 50 x 10^9/L&#xD;
&#xD;
               -  Haemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  INR ≤ 2.0&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 times the Upper Limit of Normal (ULN)&#xD;
&#xD;
               -  Albumin ≥ 2.5 g/dL&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 times the ULN&#xD;
&#xD;
               -  Alanine transaminase (ALT) ≤ 2.5 times the ULN&#xD;
&#xD;
               -  Aspartate transaminase (AST ≤ 2.5 times the ULN&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Single lesion &lt; 2 cm at the time of tumour resection.&#xD;
&#xD;
          2. The patient has previous or concomitant malignancies at other sites, except&#xD;
             effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or&#xD;
             effectively treated malignancy that has been in remission for over 5 years and highly&#xD;
             likely to have been cured.&#xD;
&#xD;
          3. Encephalopathy&#xD;
&#xD;
          4. The patient has received a major organ allograft.&#xD;
&#xD;
          5. The patient is known to be positive for the Human Immunodeficiency Virus (HIV).&#xD;
&#xD;
          6. The patient has an uncontrolled bleeding disorder.&#xD;
&#xD;
          7. The patient has uncontrolled congestive heart failure or hypertension, unstable heart&#xD;
             disease (coronary artery disease or myocardial infarction) or uncontrolled arrhythmia&#xD;
             at the time of enrolment.&#xD;
&#xD;
          8. The patient has psychiatric or addictive disorders that may compromise his/her ability&#xD;
             to give informed consent, or to comply with the study procedures.&#xD;
&#xD;
          9. The patient has other concurrent severe medical problems, unrelated to the malignancy,&#xD;
             that would significantly limit full compliance with the study or expose the patient to&#xD;
             unacceptable risk.&#xD;
&#xD;
         10. The patient has received any investigational or non-registered medicinal product (drug&#xD;
             or vaccine) within the 30 days preceding the date of enrolment, or plans to receive&#xD;
             such a drug during the study period.&#xD;
&#xD;
         11. For female patients: the patient is pregnant or lactating.&#xD;
&#xD;
         12. Insufficient DNA/RNA for genome analysis at baseline&#xD;
&#xD;
         13. Insufficient cells for immunology analysis at baseline (Singapore sites only)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pierce Chow, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Centre, Singapore</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Malaya Medical Centre</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>59100</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Medical Centre, Philippines</name>
      <address>
        <city>Manila</city>
        <zip>1605</zip>
        <country>Philippines</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>119228</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Singapore General Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>169608</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Centre Singapore</name>
      <address>
        <city>Singapore</city>
        <zip>169610</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Institute Thailand</name>
      <address>
        <city>Bangkok</city>
        <zip>10400</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Malaysia</country>
    <country>Philippines</country>
    <country>Singapore</country>
    <country>Thailand</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>June 7, 2021</last_update_submitted>
  <last_update_submitted_qc>June 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Intra-tumour heterogeneity</keyword>
  <keyword>Cancer immunotherapy</keyword>
  <keyword>Tumour microenvironment</keyword>
  <keyword>Driver mutations</keyword>
  <keyword>Precision Medicine</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>
  <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/NCT03267641
org study id: AHCC07
nct id: NCT03267641
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world but the 2nd most
      important cause of cancer death. Because of its highly heterogeneous nature, the current
      approach to identifying druggable targets have not delivered efficacious therapies in HCC and
      is a main reason for the high case fatality. Even when surgical resection is potentially
      curative in early disease, tumor recurrence remains high and long term survival poor because
      of the absence of useful adjuvant therapy.

      To address these unmet needs, the investigators bring together internationally recognized
      scientists from genomics and immunology and established clinician investigators in a
      synergistic team. This TCR capitalizes on recent collaborative advances made by the PIs in
      the consortium. The investigators have shown through multi-region sampling of freshly
      resected HCC and phylogenetic analysis, that significant intra-tumoral heterogeneity exists
      and have identified the specific positions of known clonal drivers. Simultaneously the
      investigators have analyzed the immune landscape of the tumor microenvironment with deep
      immune-phenotyping and found unique inter-patient immune landscapes predictive of clinical
      trajectory.

      This TCR is a prospective study that samples resected HCC from multi-ethnic sites within the
      established Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group, which has enrolled
      approximately 1000 patients through 6 multi-center trials in 35 centers in the region.
      Clinical trajectories are tracked and genomic and immunological studies are repeated when
      tumors recu r, to confirm clonally dominant driver mutations and immunological processes that
      are targetable. Concurrently, representative pre-clinical models will be developed from the
      tissues sampled.

      The investigators aim to combine these approaches to overcome the challenges posed by genomic
      heterogeneity and to guide the development of therapeutics and precision medicine in HCC.
observational model: Cohort
time perspective: Prospective
measure: Time to recurrence
time frame: From date of Complete Response (CR) to first recurrence of HCC, up to 3 years
measure: Disease-free Survival
time frame: From date of CR to first recurrence of HCC or death, due to any cause, up to 3 years
measure: Disease-free Specific Survival
time frame: From date of CR to first recurrence of HCC or death, due to HCC, up to 3 years
measure: Overall Survival
time frame: From diagnosis to date of death due to any cause, up to 3 years
Tumour samples Blood samples Urine samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: 80 Years
healthy volunteers: No
last name: Pierce Chow, MD, PhD
role: Principal Investigator
affiliation: National Cancer Centre, Singapore
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Malaysia
country: Philippines
country: Singapore
country: Thailand
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
sharing ipd: Undecided