<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/NCT03037437</url>
  </required_header>
  <id_info>
    <org_study_id>CTMS 16-0076</org_study_id>
    <secondary_id>HSC20160515H</secondary_id>
    <nct_id>NCT03037437</nct_id>
  </id_info>
  <brief_title>Sorafenib Induced Autophagy Using Hydroxychloroquine in Hepatocellular Cancer</brief_title>
  <official_title>Modulation of Sorafenib Induced Autophagy Using Hydroxychloroquine in Hepatocellular Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Health Science Center at San Antonio</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Texas Health Science Center at San Antonio</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The PI is studying if sorafenib/hydroxychloroquine (HCQ) will have improved efficacy when&#xD;
      compared to sorafenib alone and in patients progressing of sorafenib the addition of HCQ&#xD;
      would lead to disease stability in patients with advanced hepatocellular cancer (HCC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phase 2 study with two cohorts:&#xD;
&#xD;
      Cohort 1: As second-line treatment, we will add HCQ to SOR dose the patient was tolerating at&#xD;
      the time of progression.&#xD;
&#xD;
      Cohort 2: SOR-naïve patients receive SOR 400 mg by PO twice daily on Cycle1 Day1 (C1D1). On&#xD;
      Cycle 1 Day 15, HCQ 400 mg PO daily will be started. In clinical practice, dose reduction of&#xD;
      SOR may be required. On C1D15 SOR maybe kept as starting dose or reduced for toxicity. On&#xD;
      Cycle 2 Day 1 of toxicity of HCQ and SOR will be assessed.&#xD;
&#xD;
      Each cycle is 28 days.&#xD;
&#xD;
      Blood samples will be collected at Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 to assess&#xD;
      for biomarkers.&#xD;
&#xD;
      Disease evaluation every 2 cycles.&#xD;
&#xD;
      Dose reductions due to adverse events are allowed for both sorafenib per standard of care&#xD;
      and/or HCQ for grade 3 or more adverse event was related to study medication. Dose reductions&#xD;
      are also permitted based on investigator clinical decision.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 16, 2017</start_date>
  <completion_date type="Anticipated">March 2025</completion_date>
  <primary_completion_date type="Anticipated">March 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to tumor progression evaluated via tumor imaging</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Computerized axial tomography (CAT) Scan or Magnetic resonance imaging (MRI) will be done at Screening, then every other cycle and evaluated using RECIST version 1.1</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">68</enrollment>
  <condition>Hepatocellular Cancer</condition>
  <arm_group>
    <arm_group_label>No prior systemic treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sorafenib (SOR)-naïve patients receive SOR 400 mg by PO twice daily on Cycle1/Day1 (C1D1). In clinical practice, dose reduction of SOR is often required. Therefore, on C1D15, the clinician will dose-reduce sorafenib based on toxicity and hydroxychloroquine (HCQ) 400 mg PO daily will be started. C2D1 of each cohort, toxicity of HCQ will be assessed. Dose reductions due to adverse events (AEs) to each agent are allowed for SOR per standard of care and/or HCQ for grade 3+ AE.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Progress on sorafenib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>As second-line treatment, we will add hydroxychloroquine (HCQ) to sorafenib (SOR) dose the patient was tolerating at the time of progression.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib (SOR)</intervention_name>
    <description>Patients will receive SOR 400 mg by PO twice daily on Cycle1/Day1 (C1D1).</description>
    <arm_group_label>No prior systemic treatment</arm_group_label>
    <arm_group_label>Progress on sorafenib</arm_group_label>
    <other_name>Nexavar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine (HCQ)</intervention_name>
    <description>400mg by mouth daily</description>
    <arm_group_label>No prior systemic treatment</arm_group_label>
    <arm_group_label>Progress on sorafenib</arm_group_label>
    <other_name>Plaquenil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cytologically or histologically confirmed advanced or metastatic HCC. If no&#xD;
             histological diagnosis, patient must have imaging studies compatible with HCC.&#xD;
&#xD;
          -  Age 18 years and above&#xD;
&#xD;
          -  ECOG performance status of 0 or 1&#xD;
&#xD;
          -  Not a candidate for curative treatments (i.e., resection, transplantation)&#xD;
&#xD;
          -  Child-Pugh class A or B7 liver function&#xD;
&#xD;
          -  Measurable disease as defined by RECIST 1.1&#xD;
&#xD;
          -  Patients who received prior local therapy (e.g., TACE) are eligible.&#xD;
&#xD;
          -  Documented virology status of hepatitis, as confirmed by screening HBsAg, anti-HBc,&#xD;
             and/or anti-HCV&#xD;
&#xD;
          -  Life expectancy&gt; 3 months&#xD;
&#xD;
          -  For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile&#xD;
             (absence of ovaries and/or uterus): agreement to use two adequate methods of&#xD;
             contraception. For men: agreement to use a barrier method of contraception during the&#xD;
             treatment period&#xD;
&#xD;
          -  Hematologic, Biochemical, and Organ Function within 7 days prior to Cycle 1 Day 1:&#xD;
             Granulocyte count &gt; 1500/mm3, Platelet count &gt; 75,000/ mm3, Hemoglobin &gt; 8 g/dL; Total&#xD;
             bilirubin &lt; 2.0; Albumin &gt; 2.8g/dl; AST (SGOT) and ALT (SGPT) &lt; 5 x ULN; Serum&#xD;
             creatinine&lt; 1.5 x ULN&#xD;
&#xD;
          -  Cohort 1 (with sorafenib): No previous systemic therapy including sorafenib or&#xD;
             chemotherapy treatment. Previous TACE and local treatments are permitted.&#xD;
&#xD;
          -  Cohort 2 (on progression of sorafenib): Patients who have received prior sorafenib&#xD;
             therapy for at least 4 weeks and has confirmation of disease progression on CT/MRI.&#xD;
             Prior surgery or local therapy within 4 weeks prior to Cycle 1 Day 1, with the&#xD;
             exception of palliative radiation therapy to the bone&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients receiving prior therapy with HCQ.&#xD;
&#xD;
          -  Patients with uncontrolled brain metastases. Patients with brain metastases must be&#xD;
             asymptomatic and off corticosteroids for at least one week.&#xD;
&#xD;
          -  Due to risk of disease exacerbation, patients with psoriasis are ineligible unless the&#xD;
             disease is well controlled, and they are under the care of a specialist for the&#xD;
             disorder who agrees to monitor the patient for exacerbations.&#xD;
&#xD;
          -  Patients with previously documented macular degeneration or or untreated diabetic&#xD;
             retinopathy (stable retinopathy is allowed).&#xD;
&#xD;
          -  Patients may not be receiving any other investigational agents.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to HCQ.&#xD;
&#xD;
          -  Patients requiring the use of enzyme-inducing anti-epileptic medication (phenytoin,&#xD;
             carbamazepine, phenobarbital, primidone or oxcarbazepine) are not eligible for entry&#xD;
             into the study.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  QTc &gt; 500 milliseconds (ms) at baseline.&#xD;
&#xD;
          -  Gastrointestinal tract disease resulting in an inability to take oral medication or a&#xD;
             requirement for IV alimentation, prior surgical procedures affecting absorption, or&#xD;
             active peptic ulcer disease. Patients with NG-tube, J-tube, or G-tube will not be&#xD;
             allowed to participate.&#xD;
&#xD;
          -  Pregnant women are excluded from this study because sorafenib has the potential for&#xD;
             teratogenic or abortifacient effects. For this reason, women of childbearing potential&#xD;
             and men must also agree to use adequate contraception (hormonal or barrier method of&#xD;
             birth control) prior to study entry and for the duration of study participation.&#xD;
&#xD;
          -  Should a woman become pregnant or suspect she is pregnant while participating in this&#xD;
             study, she should inform her treating physician immediately. Because there is an&#xD;
             unknown but potential risk for adverse events in nursing infants secondary to&#xD;
             treatment of the mother with sorafenib, breastfeeding should be discontinued.&#xD;
&#xD;
          -  Informed Consent - No study specific procedures will be performed without a written&#xD;
             and signed informed consent document. Patients who do not demonstrate the ability to&#xD;
             understand or the willingness to sign the written informed consent document will be&#xD;
             excluded from study entry.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sukeshi Patel Arora, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Therapy &amp; Research Center University of Texas Health Science Center San Antonio</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Epp Goodwin</last_name>
    <phone>210-450-5798</phone>
    <email>ctrcreferral@uthscsa.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sukeshi Patel Arora, MD</last_name>
    <phone>210-450-1015</phone>
    <email>aroras@uthscsa.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Texas Health Cancer Center</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Epp Goodwin</last_name>
      <phone>210-450-5798</phone>
      <email>goodwine@uthscsa.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>June 28, 2023</last_update_submitted>
  <last_update_submitted_qc>June 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Texas Health Science Center at San Antonio</investigator_affiliation>
    <investigator_full_name>Sukeshi Patel</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Hepatocellular Cancer</keyword>
  <keyword>Sorafenib</keyword>
  <keyword>Hydroxychloroquine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Neoplasms</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>Hydroxychloroquine</mesh_term>
    <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/NCT03037437
org study id: CTMS 16-0076
secondary id: HSC20160515H
nct id: NCT03037437
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The PI is studying if sorafenib/hydroxychloroquine (HCQ) will have improved efficacy when
      compared to sorafenib alone and in patients progressing of sorafenib the addition of HCQ
      would lead to disease stability in patients with advanced hepatocellular cancer (HCC).
Phase 2 study with two cohorts:

      Cohort 1: As second-line treatment, we will add HCQ to SOR dose the patient was tolerating at
      the time of progression.

      Cohort 2: SOR-naïve patients receive SOR 400 mg by PO twice daily on Cycle1 Day1 (C1D1). On
      Cycle 1 Day 15, HCQ 400 mg PO daily will be started. In clinical practice, dose reduction of
      SOR may be required. On C1D15 SOR maybe kept as starting dose or reduced for toxicity. On
      Cycle 2 Day 1 of toxicity of HCQ and SOR will be assessed.

      Each cycle is 28 days.

      Blood samples will be collected at Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 to assess
      for biomarkers.

      Disease evaluation every 2 cycles.

      Dose reductions due to adverse events are allowed for both sorafenib per standard of care
      and/or HCQ for grade 3 or more adverse event was related to study medication. Dose reductions
      are also permitted based on investigator clinical decision.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time to tumor progression evaluated via tumor imaging
time frame: Through study completion, an average of 1 year
description: Computerized axial tomography (CAT) Scan or Magnetic resonance imaging (MRI) will be done at Screening, then every other cycle and evaluated using RECIST version 1.1
arm group label: No prior systemic treatment
arm group type: Experimental
description: Sorafenib (SOR)-naïve patients receive SOR 400 mg by PO twice daily on Cycle1/Day1 (C1D1). In clinical practice, dose reduction of SOR is often required. Therefore, on C1D15, the clinician will dose-reduce sorafenib based on toxicity and hydroxychloroquine (HCQ) 400 mg PO daily will be started. C2D1 of each cohort, toxicity of HCQ will be assessed. Dose reductions due to adverse events (AEs) to each agent are allowed for SOR per standard of care and/or HCQ for grade 3+ AE.
arm group label: Progress on sorafenib
arm group type: Experimental
description: As second-line treatment, we will add hydroxychloroquine (HCQ) to sorafenib (SOR) dose the patient was tolerating at the time of progression.
intervention type: Drug
intervention name: Sorafenib (SOR)
description: Patients will receive SOR 400 mg by PO twice daily on Cycle1/Day1 (C1D1).
arm group label: No prior systemic treatment
arm group label: Progress on sorafenib
other name: Nexavar
intervention type: Drug
intervention name: Hydroxychloroquine (HCQ)
description: 400mg by mouth daily
arm group label: No prior systemic treatment
arm group label: Progress on sorafenib
other name: Plaquenil
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Sukeshi Patel Arora, MD
role: Principal Investigator
affiliation: Cancer Therapy & Research Center University of Texas Health Science Center San Antonio
last name: Epp Goodwin
phone: 210-450-5798
email: ctrcreferral@uthscsa.edu
last name: Sukeshi Patel Arora, MD
phone: 210-450-1015
email: aroras@uthscsa.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The University of Texas Health Science Center at San Antonio
investigator full name: Sukeshi Patel
investigator title: Principal Investigator
mesh term: Liver Neoplasms
mesh term: Carcinoma, Hepatocellular
mesh term: Hydroxychloroquine
mesh term: Sorafenib