<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/NCT01666756</url>
  </required_header>
  <id_info>
    <org_study_id>11043</org_study_id>
    <secondary_id>NCI-2012-01324</secondary_id>
    <secondary_id>5P01CA154295-02</secondary_id>
    <nct_id>NCT01666756</nct_id>
  </id_info>
  <brief_title>Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer</brief_title>
  <official_title>A Phase I Open Label Study Investigating the Combination of KD018 and Sorafenib (Nexavar) in Patients With Advanced Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>City of Hope Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>City of Hope Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of Chinese herbal formulation&#xD;
      PHY906 when given together with sorafenib tosylate in treating patients with advanced liver&#xD;
      cancer. Biological therapies, such as Chinese herbal formulation PHY906, may interfere with&#xD;
      the growth of tumor cells and slow the growth of tumors. Sorafenib tosylate may stop the&#xD;
      growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib&#xD;
      tosylate may also stop the growth of liver cancer by blocking blood flow to the tumor. Giving&#xD;
      Chinese herbal formulation PHY906 together with sorafenib tosylate may work better in&#xD;
      treating advanced liver cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To characterize the safety and tolerability of KD018 (Chinese herbal formulation PHY906)&#xD;
      in combination with daily sorafenib (sorafenib tosylate) and to determine the maximum&#xD;
      tolerated dose (MTD) of the combination of KD018 plus sorafenib to bring forward into phase&#xD;
      2.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To describe the efficacy of the combination of KD018 plus sorafenib at the explored&#xD;
      dose-levels in terms of best overall response as defined by Response Evaluation Criteria in&#xD;
      Solid Tumors (RECIST) guidelines.&#xD;
&#xD;
      II. To assess the safety and tolerability of the combination of KD018 plus sorafenib as&#xD;
      measured by the rate and severity of adverse events (AEs).&#xD;
&#xD;
      III. To determine the steady state of sorafenib after KD018 exposure at pre-dose and 1 hour&#xD;
      and 2 hours post-dose at the explored combination dose-levels using concentrations at&#xD;
      pre-dose (Cmin) and at 1 hour (C1h) and 2 hours (C2h) post-dose.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the effect of treatment on soluble markers of angiogenesis, fibroblast growth&#xD;
      factor (FGF), vascular endothelial growth factor (VEGF), placental growth factor (PLGF),&#xD;
      soluble vascular endothelial growth factor receptor 1 (sVEGFR1), sVEGFR2, apoptosis (i.e. M30&#xD;
      monoclonal antibody [M30] and M65) and on the insulin-like growth factor (IGF) axis including&#xD;
      molecules such as IGF-binding protein 2 (IGFII).&#xD;
&#xD;
      II. To correlate the above soluble biomarker measurements with clinical endpoints.&#xD;
&#xD;
      III. To examine the correlation between the soluble biomarkers.&#xD;
&#xD;
      IV. To examine the predictive relationship of immunohistochemical tumor biomarkers at&#xD;
      baseline, i.e. phosphorylated ribosomal protein S6 kinase (pS6), p-protein kinase B (pAKT),&#xD;
      p-mitogen-activated protein kinase 1 (ERK), p-mitogen-activated protein kinase kinase (pMEK),&#xD;
      hypoxia-inducible factor 2, alpha subunit (HIF2a), phosphatase and tensin homolog gene&#xD;
      (PTEN), signal transducer and activator of transcription 3 (acute-phase response factor)&#xD;
      (STAT3) and tumor protein p53 (p53), as well as of mutational status, i.e. p53,&#xD;
      phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) and PTEN,&#xD;
      with efficacy endpoints (time to progression [TTP]).&#xD;
&#xD;
      V. To determine if soluble apoptosis markers (M30/M65) correlate with proliferative markers&#xD;
      at baseline (proliferation-related Ki-67 antigen [Ki67] and p53) in archival tumor samples.&#xD;
&#xD;
      VI. To examine the relationship of immunohistochemical and/or soluble biomarkers with&#xD;
      subgroup classification namely, patients with hepatitis B virus (HBV), patients with&#xD;
      hepatitis C virus (HCV) and patients with other etiologies.&#xD;
&#xD;
      VII. To explore potential biomarker differences within patient subgroups, namely, patients&#xD;
      with HBV, patients with HCV and patients with other etiologies.&#xD;
&#xD;
      VIII. To determine the effect of KD018 on cytokine/chemokine levels including interleukin&#xD;
      (IL)-2, IL-4, IL-5, IL-6, IL-10, monocyte chemotactic protein 1 (MCP-1), tumor necrosis&#xD;
      factor (TNF)-alpha, interferon (IFN)-alpha, VEGF, FGF-basic (b), sargramostim (GM-CSF),&#xD;
      filgrastim (G-CSF).&#xD;
&#xD;
      IX. To explore potential relationships between efficacy and Cmin of sorafenib after&#xD;
      co-administration with KD018 and between occurrence of adverse events and C1h/C2h endpoints&#xD;
      (efficacy, safety, pharmacokinetics [PK]).&#xD;
&#xD;
      OUTLINE: This is a phase I, dose-escalation study of Chinese herbal formulation PHY906.&#xD;
&#xD;
      Patients receive Chinese herbal formulation PHY906 orally (PO) twice daily (BID) on days 1-4,&#xD;
      8-11, 15-18, 21-24 and sorafenib tosylate PO BID on days 1-28. Courses repeat every 28 days&#xD;
      in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 11, 2014</start_date>
  <completion_date type="Actual">May 29, 2020</completion_date>
  <primary_completion_date type="Actual">May 29, 2020</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>Recommended phase II dose, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events as determined by NCI CTCAE version 4</measure>
    <time_frame>Up to 4 weeks after completion of study treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious adverse events as determined by NCI CTCAE version 4</measure>
    <time_frame>Up to 4 weeks after completion of study treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Discontinuation rate</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose adjustment rate</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response in terms of best overall response, assessed using RECIST</measure>
    <time_frame>Up to 6 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sorafenib tosylate concentration after co-administration with Chinese herbal formulation PHY906</measure>
    <time_frame>Baseline; 1 hour post-dose; 2 hours post-dose</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in cytokine/chemokine levels</measure>
    <time_frame>Baseline to up to 6 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in levels of soluble biomarkers</measure>
    <time_frame>Baseline to up to 6 years</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">18</enrollment>
  <condition>Adult Primary Hepatocellular Carcinoma</condition>
  <condition>Advanced Adult Primary Liver Cancer</condition>
  <condition>Advanced Adult Hepatocellular Carcinoma</condition>
  <condition>BCLC Stage B Adult Hepatocellular Carcinoma</condition>
  <condition>BCLC Stage C Adult Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (Chinese herbal formulation PHY906 and sorafenib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive Chinese herbal formulation PHY906 PO BID on days 1-4, 8-11, 15-18, 21-24 and sorafenib tosylate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Chinese herbal formulation PHY906</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (Chinese herbal formulation PHY906 and sorafenib)</arm_group_label>
    <other_name>PHY-906</other_name>
    <other_name>KD018</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sorafenib tosylate</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (Chinese herbal formulation PHY906 and sorafenib)</arm_group_label>
    <other_name>BAY 43-9006</other_name>
    <other_name>BAY 43-9006 Tosylate Salt</other_name>
    <other_name>BAY 54-9085</other_name>
    <other_name>Nexavar</other_name>
    <other_name>SFN</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (Chinese herbal formulation PHY906 and sorafenib)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>pharmacological study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (Chinese herbal formulation PHY906 and sorafenib)</arm_group_label>
    <other_name>pharmacological studies</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to take oral drugs&#xD;
&#xD;
          -  Diagnosis of advanced hepatocellular carcinoma (HCC) according to the American&#xD;
             Association for the Study of Liver Diseases (AASLD) guidelines&#xD;
&#xD;
          -  HCC stage B or C according to the Barcelona Clinic Liver Cancer (BCLC)&#xD;
&#xD;
          -  Previous or current use of sorafenib allowed&#xD;
&#xD;
          -  Measurable disease according to RECIST, i.e. at least one measurable lesion; this&#xD;
             lesion should not have been previously treated with local therapy; a treated lesion&#xD;
             may be used where these lesions are the only lesions available for evaluation and have&#xD;
             shown definite progression since their last local treatment; local therapy must have&#xD;
             been completed at least four weeks prior to baseline evaluation&#xD;
&#xD;
          -  Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or&#xD;
             1&#xD;
&#xD;
          -  Cirrhotic status of current Child-Pugh class A and B with no encephalopathy and no&#xD;
             ascites (ascites controlled by diuretics is also excluded in this study); Child-Pugh&#xD;
             status should be calculated based on clinical findings and laboratory results during&#xD;
             the screening period&#xD;
&#xD;
          -  For patients with positive HBV-deoxyribonucleic acid (DNA) and/or positive of&#xD;
             hepatitis B surface antigen (HBsAg) results, they must be treated with anti-virals, as&#xD;
             prophylaxis at least 1-2 weeks prior to receiving study drug, cycle 1, day 1&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1.5 x 10^9/L&#xD;
&#xD;
          -  Platelets &gt;= 75000 x 10^6/L&#xD;
&#xD;
          -  Hemoglobin (Hgb) &gt;= 9 g/dL&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) =&lt; 5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Ability to understand and willingness to sign a written informed consent and to be&#xD;
             able to follow the visit schedule&#xD;
&#xD;
          -  Life expectancy of approximately 6 months&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control or abstinence) prior to study entry and&#xD;
             for three months following duration of study participation; should a woman become&#xD;
             pregnant, or suspect that she is pregnant while participating on the trial, she should&#xD;
             inform her treating physician immediately&#xD;
&#xD;
          -  All subjects must have the ability to understand and the willingness to sign a written&#xD;
             informed consent&#xD;
&#xD;
          -  Previous or current use of sorafenib and previous use of tamoxifen is allowed as&#xD;
             previous systemic therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients currently receiving any anti-cancer therapy, except sorafenib, or who have&#xD;
             received any local anti-cancer therapy =&lt; 4 weeks prior to baseline computed&#xD;
             tomography (CT)/magnetic resonance imaging (MRI) scan, prior to cycle 1 treatment&#xD;
&#xD;
          -  Active bleeding during the last 30 days prior to cycle 1 treatment including variceal&#xD;
             bleeding (esophageal varices should be treated according to standard practice e.g.&#xD;
             ligation/banding and procedure completed 30 days prior to cycle 1 treatment)&#xD;
&#xD;
          -  Patients with a known hypersensitivity to KD018 or known hypersensitivity to sorafenib&#xD;
             or contraindications to sorafenib based on the local sorafenib label&#xD;
&#xD;
          -  Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not&#xD;
             mandatory)&#xD;
&#xD;
          -  Any severe and/or uncontrolled medical conditions including:&#xD;
&#xD;
               -  Unstable angina pectoris, symptomatic congestive heart failure, myocardial&#xD;
                  infarction =&lt; 6 months prior to cycle 1 treatment, serious uncontrolled cardiac&#xD;
                  arrhythmia, uncontrolled hypertension&#xD;
&#xD;
               -  Previous transient ischemic attack (TIA), cerebral vascular accident (CVA),&#xD;
                  symptomatic posterior vitreous detachment (PVD) within last 6 months of cycle 1&#xD;
                  treatment&#xD;
&#xD;
               -  Congenital long QT syndrome&#xD;
&#xD;
               -  Patients with active alcohol intake&#xD;
&#xD;
               -  Acute and chronic, active infectious disorders and nonmalignant medical illnesses&#xD;
                  that are uncontrolled or whose control may be jeopardized by the complications of&#xD;
                  this study therapy, in the opinion of the investigator, except chronic HBV or HCV&#xD;
&#xD;
               -  Impairment of gastrointestinal function or who have gastrointestinal disease that&#xD;
                  may significantly alter the absorption of study drugs (e.g., ulcerative disease,&#xD;
                  uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)&#xD;
&#xD;
          -  Patients receiving chronic treatment with corticosteroids (except for intermittent&#xD;
             topical or local injection or aldosterone) or another immunosuppressive agent&#xD;
&#xD;
          -  Patients treated with drugs known to be strong inhibitors or inducers of isoenzyme&#xD;
             cytochrome P450, family 3, subfamily A (CYP3A) unless the drugs are medically&#xD;
             necessary and no substitutes are available&#xD;
&#xD;
          -  Patients who have undergone major surgery =&lt; 2 weeks prior to starting study drug or&#xD;
             who have not recovered from surgery&#xD;
&#xD;
          -  Patients who have received an investigative drug or therapy within the last 30 days&#xD;
             prior to cycle 1 treatment&#xD;
&#xD;
          -  Pregnant and/or breastfeeding women&#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>Joseph Chao, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>City of Hope Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>January 26, 2021</last_update_submitted>
  <last_update_submitted_qc>January 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2021</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>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
    <mesh_term>Liver Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sorafenib</mesh_term>
  </intervention_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/NCT01666756
org study id: 11043
secondary id: NCI-2012-01324
secondary id: 5P01CA154295-02
nct id: NCT01666756
lead sponsor: 
collaborator: 
has dmc: Yes
This phase I trial studies the side effects and best dose of Chinese herbal formulation
      PHY906 when given together with sorafenib tosylate in treating patients with advanced liver
      cancer. Biological therapies, such as Chinese herbal formulation PHY906, may interfere with
      the growth of tumor cells and slow the growth of tumors. Sorafenib tosylate may stop the
      growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib
      tosylate may also stop the growth of liver cancer by blocking blood flow to the tumor. Giving
      Chinese herbal formulation PHY906 together with sorafenib tosylate may work better in
      treating advanced liver cancer.
PRIMARY OBJECTIVES:

      I. To characterize the safety and tolerability of KD018 (Chinese herbal formulation PHY906)
      in combination with daily sorafenib (sorafenib tosylate) and to determine the maximum
      tolerated dose (MTD) of the combination of KD018 plus sorafenib to bring forward into phase
      2.

      SECONDARY OBJECTIVES:

      I. To describe the efficacy of the combination of KD018 plus sorafenib at the explored
      dose-levels in terms of best overall response as defined by Response Evaluation Criteria in
      Solid Tumors (RECIST) guidelines.

      II. To assess the safety and tolerability of the combination of KD018 plus sorafenib as
      measured by the rate and severity of adverse events (AEs).

      III. To determine the steady state of sorafenib after KD018 exposure at pre-dose and 1 hour
      and 2 hours post-dose at the explored combination dose-levels using concentrations at
      pre-dose (Cmin) and at 1 hour (C1h) and 2 hours (C2h) post-dose.

      TERTIARY OBJECTIVES:

      I. To assess the effect of treatment on soluble markers of angiogenesis, fibroblast growth
      factor (FGF), vascular endothelial growth factor (VEGF), placental growth factor (PLGF),
      soluble vascular endothelial growth factor receptor 1 (sVEGFR1), sVEGFR2, apoptosis (i.e. M30
      monoclonal antibody [M30] and M65) and on the insulin-like growth factor (IGF) axis including
      molecules such as IGF-binding protein 2 (IGFII).

      II. To correlate the above soluble biomarker measurements with clinical endpoints.

      III. To examine the correlation between the soluble biomarkers.

      IV. To examine the predictive relationship of immunohistochemical tumor biomarkers at
      baseline, i.e. phosphorylated ribosomal protein S6 kinase (pS6), p-protein kinase B (pAKT),
      p-mitogen-activated protein kinase 1 (ERK), p-mitogen-activated protein kinase kinase (pMEK),
      hypoxia-inducible factor 2, alpha subunit (HIF2a), phosphatase and tensin homolog gene
      (PTEN), signal transducer and activator of transcription 3 (acute-phase response factor)
      (STAT3) and tumor protein p53 (p53), as well as of mutational status, i.e. p53,
      phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) and PTEN,
      with efficacy endpoints (time to progression [TTP]).

      V. To determine if soluble apoptosis markers (M30/M65) correlate with proliferative markers
      at baseline (proliferation-related Ki-67 antigen [Ki67] and p53) in archival tumor samples.

      VI. To examine the relationship of immunohistochemical and/or soluble biomarkers with
      subgroup classification namely, patients with hepatitis B virus (HBV), patients with
      hepatitis C virus (HCV) and patients with other etiologies.

      VII. To explore potential biomarker differences within patient subgroups, namely, patients
      with HBV, patients with HCV and patients with other etiologies.

      VIII. To determine the effect of KD018 on cytokine/chemokine levels including interleukin
      (IL)-2, IL-4, IL-5, IL-6, IL-10, monocyte chemotactic protein 1 (MCP-1), tumor necrosis
      factor (TNF)-alpha, interferon (IFN)-alpha, VEGF, FGF-basic (b), sargramostim (GM-CSF),
      filgrastim (G-CSF).

      IX. To explore potential relationships between efficacy and Cmin of sorafenib after
      co-administration with KD018 and between occurrence of adverse events and C1h/C2h endpoints
      (efficacy, safety, pharmacokinetics [PK]).

      OUTLINE: This is a phase I, dose-escalation study of Chinese herbal formulation PHY906.

      Patients receive Chinese herbal formulation PHY906 orally (PO) twice daily (BID) on days 1-4,
      8-11, 15-18, 21-24 and sorafenib tosylate PO BID on days 1-28. Courses repeat every 28 days
      in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recommended phase II dose, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
time frame: 28 days
measure: Adverse events as determined by NCI CTCAE version 4
time frame: Up to 4 weeks after completion of study treatment
measure: Serious adverse events as determined by NCI CTCAE version 4
time frame: Up to 4 weeks after completion of study treatment
measure: Discontinuation rate
time frame: Up to 6 years
measure: Dose adjustment rate
time frame: Up to 6 years
measure: Tumor response in terms of best overall response, assessed using RECIST
time frame: Up to 6 years
measure: Sorafenib tosylate concentration after co-administration with Chinese herbal formulation PHY906
time frame: Baseline; 1 hour post-dose; 2 hours post-dose
measure: Change in cytokine/chemokine levels
time frame: Baseline to up to 6 years
measure: Change in levels of soluble biomarkers
time frame: Baseline to up to 6 years
arm group label: Treatment (Chinese herbal formulation PHY906 and sorafenib)
arm group type: Experimental
description: Patients receive Chinese herbal formulation PHY906 PO BID on days 1-4, 8-11, 15-18, 21-24 and sorafenib tosylate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Dietary Supplement
intervention name: Chinese herbal formulation PHY906
description: Given PO
arm group label: Treatment (Chinese herbal formulation PHY906 and sorafenib)
other name: PHY-906
other name: KD018
intervention type: Drug
intervention name: sorafenib tosylate
description: Given PO
arm group label: Treatment (Chinese herbal formulation PHY906 and sorafenib)
other name: BAY 43-9006
other name: BAY 43-9006 Tosylate Salt
other name: BAY 54-9085
other name: Nexavar
other name: SFN
intervention type: Other
intervention name: laboratory biomarker analysis
description: Correlative studies
arm group label: Treatment (Chinese herbal formulation PHY906 and sorafenib)
intervention type: Other
intervention name: pharmacological study
description: Correlative studies
arm group label: Treatment (Chinese herbal formulation PHY906 and sorafenib)
other name: pharmacological studies
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joseph Chao, MD
role: Principal Investigator
affiliation: City of Hope Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Liver Neoplasms
mesh term: Sorafenib