<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/NCT02989870</url>
  </required_header>
  <id_info>
    <org_study_id>MCC-18924</org_study_id>
    <nct_id>NCT02989870</nct_id>
  </id_info>
  <brief_title>Sorafenib and Bavituximab Plus SBRT in Unresectable Hepatocellular Carcinoma</brief_title>
  <official_title>A Phase I Trial of Sorafenib and Bavituximab Plus Stereotactic Body Radiation Therapy (SBRT) for 1st Line Treatment of Unresectable Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>H. Lee Moffitt Cancer Center and Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Comprehensive Cancer Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>H. Lee Moffitt Cancer Center and Research Institute</source>
  <oversight_info>
    <has_dmc>No</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>
      This study involves a course of radiation to up to 5 tumors in the participant's liver&#xD;
      followed by systemic therapy. (Treatment using substances that travel through the&#xD;
      bloodstream, reaching and affecting cells all over the body.) The type of radiation is called&#xD;
      stereotactic body radiation therapy (SBRT). The purpose of this study is to compare the&#xD;
      effects, good and/or bad, of different doses of SBRT given along with the systemic therapies,&#xD;
      sorafenib and bavituximab. The researchers want to see which dose of radiation will work best&#xD;
      in stimulating the immune response and provide local control to the participant's liver. The&#xD;
      usual treatment for hepatocellular carcinoma that is unresectable can be transarterial&#xD;
      therapy, sorafenib alone and/or clinical trial.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No Interest. Investigator was unable to enroll any participants on study.&#xD;
  </why_stopped>
  <start_date type="Actual">March 27, 2017</start_date>
  <completion_date type="Actual">October 15, 2018</completion_date>
  <primary_completion_date type="Actual">October 15, 2018</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>Occurrence of Treatment Related Adverse Events</measure>
    <time_frame>From beginning of treatment to 30 days post-treatment, approximately 2 years</time_frame>
    <description>Safety and tolerability, as assessed by presence of adverse events, serious adverse events, dose limiting toxicity (DLTs), abnormal laboratory parameters, vital signs. A DLT is defined as any toxicity not attributable to the disease or disease-related processes under investigation, which occurs from the start of radiation up to 42 days and is considered by the Investigators to be definitely, probably, or possibly related to the treatment. A DLT will be defined as any Grade 3 or higher treatment-related toxicity that occurs during the DLT evaluation period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Up to 24 months post treatment</time_frame>
    <description>Tumor response data will be summarized for dosed participants with measurable disease at baseline. Response will be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. In addition, the immune response criteria will be utilized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Up to 24 months post treatment</time_frame>
    <description>PFS following SBRT, sorafenib, and bavituximab, will be summarized in the expansion phase arm. Progression will be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.) In addition, the immune response criteria will be utilized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 24 months post treatment</time_frame>
    <description>Overall Survival following SBRT, sorafenib, and bavituximab. OS: The length of time from beginning of study treatment to death from any cause.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>HepatoCellular Carcinoma</condition>
  <condition>Unresectable HepatoCellular Carcinoma</condition>
  <condition>Liver Cancer</condition>
  <arm_group>
    <arm_group_label>SBRT, Sorafenib and Bavituximab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This will be a 3+3 design with 3 dose cohorts. Following the dose escalation phase, an additional 6 patients will be enrolled as part of the dose expansion cohort.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic Body Radiation Therapy (SBRT)</intervention_name>
    <description>Participants will receive 3-5 fractions of radiation as determined by the dose level at time of enrollment. The starting dose level will be Dose Level 1: 8 Gy x 3 fractions for a total of 24 Gy. If sufficient treatment related toxicity is observed at the &quot;initial starting dose&quot;, then the dose will be reduced to 16 Gy in 2 fractions of 8 Gy. The dose per fraction for each participant will be provided at the time of registration based on the toxicity experience of the previous participants on study. This will be escalated to 40 Gy in 5 fractions of 8 Gy.</description>
    <arm_group_label>SBRT, Sorafenib and Bavituximab</arm_group_label>
    <other_name>radiotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>Sorafenib by mouth (PO): 200 mg twice a day (BID) then 400 mg BID.</description>
    <arm_group_label>SBRT, Sorafenib and Bavituximab</arm_group_label>
    <other_name>Nexavar</other_name>
    <other_name>Kinase inhibitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bavituximab</intervention_name>
    <description>Bavituximab intravenously (IV): 3 mg/kg every week (q wk).</description>
    <arm_group_label>SBRT, Sorafenib and Bavituximab</arm_group_label>
    <other_name>Immunotherapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Advanced, unresectable hepatocellular carcinoma (unsuitable for resection, transplant&#xD;
             or ablation)&#xD;
&#xD;
          -  Age ≥ 18&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1&#xD;
&#xD;
          -  Must have normal organ and marrow function&#xD;
&#xD;
          -  Childs-Pugh score of A or B7&#xD;
&#xD;
          -  Must have measurable/evaluable disease as per RECIST 1.1 criteria&#xD;
&#xD;
          -  Females of child-bearing potential must agree to use dual methods of contraception and&#xD;
             have a negative serum pregnancy test at screening, and male patients must use an&#xD;
             effective barrier method of contraception if sexually active with a female of&#xD;
             child-bearing potential. For both males and females, effective methods of&#xD;
             contraception must be used throughout the study and for four months following the last&#xD;
             dose.&#xD;
&#xD;
          -  Able to swallow and retain orally administered medication and does not have any&#xD;
             clinically significant gastrointestinal abnormalities that may alter absorption such&#xD;
             as malabsorption syndrome or major resection of the stomach or bowels.&#xD;
&#xD;
          -  Must be able to understand and be willing to sign the written informed consent form&#xD;
&#xD;
          -  No more than 10 lesions in the liver&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have received radiation therapy, major surgery, other locoregional therapy, within 4&#xD;
             weeks prior to the first date of SBRT&#xD;
&#xD;
          -  Prior radiotherapy to the region of the liver that would result in excessive doses to&#xD;
             normal tissues due to overlap of radiation therapy fields&#xD;
&#xD;
          -  Prior selective internal radiotherapy/hepatic arterial Yttrium therapy, at any time&#xD;
&#xD;
          -  Any one hepatocellular carcinoma &gt; 15 cm&#xD;
&#xD;
          -  Total maximal sum of hepatocellular carcinomas or a single conglomerate HCC &gt; 20 cm&#xD;
&#xD;
          -  Direct tumor extension into the stomach, duodenum, small bowel or large bowel&#xD;
&#xD;
          -  Measureable common or main branch biliary duct involvement with HCC&#xD;
&#xD;
          -  Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC)&#xD;
             &gt; 3.0 cm, in sum of maximal diameters (e.g., presence of one 3.4 cm metastatic lymph&#xD;
             node or two 2 cm lung lesions). Note that benign non-enhancing periportal&#xD;
             lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if&#xD;
             the sum of enlarged nodes is &gt; 2.0 cm.&#xD;
&#xD;
          -  Use of regular phenytoin, carbamazepine, hypericum perforatum [also known as St.&#xD;
             John's wort] or rifampin&#xD;
&#xD;
          -  Have received sorafenib or other systemic therapies for treatment of HCC in the past.&#xD;
&#xD;
          -  Active autoimmune disease; Patients with type I diabetes mellitus, hypothyroidism&#xD;
             requiring only hormone replacement, psoriasis not requiring systemic treatment, or&#xD;
             vitiligo are permitted for enrollment.&#xD;
&#xD;
          -  No active malignancy except for nonmelanoma skin cancer or in situ cervical cancer.&#xD;
             Patients surviving a cancer that was curatively treated and without evidence of&#xD;
             disease for more than 3 years before the trial are allowed.&#xD;
&#xD;
          -  Myocardial infarction within past 6 months, congestive heart failure, unstable angina,&#xD;
             active cardiomyopathy, unstable ventricular arrhythmia&#xD;
&#xD;
          -  Congenital long QT syndrome&#xD;
&#xD;
          -  Previous stroke within past 12 months&#xD;
&#xD;
          -  Anti-coagulant therapy, bleeding or clotting disorder&#xD;
&#xD;
          -  Symptomatic metastatic brain or meningeal tumors&#xD;
&#xD;
          -  Presence of a non-healing wound, non-healing ulcer, or bone fracture&#xD;
&#xD;
          -  History of organ allograft (including corneal transplant)&#xD;
&#xD;
          -  Known or suspected allergy or hypersensitivity to any of the study drugs, study drug&#xD;
             classes, or excipients of the formulations given during the course of this trial&#xD;
&#xD;
          -  Women who are pregnant or breast-feeding&#xD;
&#xD;
          -  Any condition which, in the investigator's opinion, makes the patient unsuitable for&#xD;
             trial participation&#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>Jessica Frakes, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>H. Lee Moffitt Cancer Center and Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center and Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>December 8, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 12, 2016</study_first_posted>
  <last_update_submitted>June 3, 2020</last_update_submitted>
  <last_update_submitted_qc>June 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Liver Disease</keyword>
  <keyword>Child-Pugh Class A</keyword>
  <keyword>Child-Pugh Class B7</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>Sorafenib</mesh_term>
    <mesh_term>Bavituximab</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/NCT02989870
org study id: MCC-18924
nct id: NCT02989870
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study involves a course of radiation to up to 5 tumors in the participant's liver
      followed by systemic therapy. (Treatment using substances that travel through the
      bloodstream, reaching and affecting cells all over the body.) The type of radiation is called
      stereotactic body radiation therapy (SBRT). The purpose of this study is to compare the
      effects, good and/or bad, of different doses of SBRT given along with the systemic therapies,
      sorafenib and bavituximab. The researchers want to see which dose of radiation will work best
      in stimulating the immune response and provide local control to the participant's liver. The
      usual treatment for hepatocellular carcinoma that is unresectable can be transarterial
      therapy, sorafenib alone and/or clinical trial.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of Treatment Related Adverse Events
time frame: From beginning of treatment to 30 days post-treatment, approximately 2 years
description: Safety and tolerability, as assessed by presence of adverse events, serious adverse events, dose limiting toxicity (DLTs), abnormal laboratory parameters, vital signs. A DLT is defined as any toxicity not attributable to the disease or disease-related processes under investigation, which occurs from the start of radiation up to 42 days and is considered by the Investigators to be definitely, probably, or possibly related to the treatment. A DLT will be defined as any Grade 3 or higher treatment-related toxicity that occurs during the DLT evaluation period.
measure: Objective Response Rate (ORR)
time frame: Up to 24 months post treatment
description: Tumor response data will be summarized for dosed participants with measurable disease at baseline. Response will be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. In addition, the immune response criteria will be utilized.
measure: Progression Free Survival (PFS)
time frame: Up to 24 months post treatment
description: PFS following SBRT, sorafenib, and bavituximab, will be summarized in the expansion phase arm. Progression will be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.) In addition, the immune response criteria will be utilized.
measure: Overall Survival (OS)
time frame: Up to 24 months post treatment
description: Overall Survival following SBRT, sorafenib, and bavituximab. OS: The length of time from beginning of study treatment to death from any cause.
arm group label: SBRT, Sorafenib and Bavituximab
arm group type: Experimental
description: This will be a 3+3 design with 3 dose cohorts. Following the dose escalation phase, an additional 6 patients will be enrolled as part of the dose expansion cohort.
intervention type: Radiation
intervention name: Stereotactic Body Radiation Therapy (SBRT)
description: Participants will receive 3-5 fractions of radiation as determined by the dose level at time of enrollment. The starting dose level will be Dose Level 1: 8 Gy x 3 fractions for a total of 24 Gy. If sufficient treatment related toxicity is observed at the "initial starting dose", then the dose will be reduced to 16 Gy in 2 fractions of 8 Gy. The dose per fraction for each participant will be provided at the time of registration based on the toxicity experience of the previous participants on study. This will be escalated to 40 Gy in 5 fractions of 8 Gy.
arm group label: SBRT, Sorafenib and Bavituximab
other name: radiotherapy
intervention type: Drug
intervention name: Sorafenib
description: Sorafenib by mouth (PO): 200 mg twice a day (BID) then 400 mg BID.
arm group label: SBRT, Sorafenib and Bavituximab
other name: Nexavar
other name: Kinase inhibitor
intervention type: Drug
intervention name: Bavituximab
description: Bavituximab intravenously (IV): 3 mg/kg every week (q wk).
arm group label: SBRT, Sorafenib and Bavituximab
other name: Immunotherapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jessica Frakes, M.D.
role: Principal Investigator
affiliation: H. Lee Moffitt Cancer Center and Research Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Sorafenib
mesh term: Bavituximab