<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/NCT01697371</url>
  </required_header>
  <id_info>
    <org_study_id>5120022</org_study_id>
    <nct_id>NCT01697371</nct_id>
  </id_info>
  <brief_title>Proton Therapy in the Treatment of Liver Metastases</brief_title>
  <official_title>Phase I-II Trial of Stereotactic Body Proton Therapy for Patients With Liver Metastases</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Loma Linda University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Loma Linda University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Local control of hepatic metastases appears to be a major determinant of overall survival.&#xD;
      However, many patients are not suitable for resection due to medical or surgical reasons.&#xD;
      Therefore, there is an important role for a treatment that can provide the equivalent of&#xD;
      tumor resection with minimal morbidity. Stereotactic body radiotherapy (SBRT) delivers an&#xD;
      ablative regimen of highly focused external beam radiotherapy that targets one or more&#xD;
      discrete extracranial lesions. Published reports using SBRT to treat liver metastases have&#xD;
      shown actuarial local control rates ranging from 50-100% with higher doses associated with&#xD;
      better local control.&#xD;
&#xD;
      In patients with metastatic liver disease, aggressive local therapy using modern radiotherapy&#xD;
      techniques are promising and project to have a substantial role in the treatment of&#xD;
      metastatic liver cancer to treat unresectable disease. The dosimetric advantage of proton&#xD;
      therapy may lead to improved clinical outcomes with less morbidity, however, there is no&#xD;
      clinical data to confirm this assertion. We thus propose a phase I study to determine the&#xD;
      feasibility and safety of stereotactic body proton therapy in patients with liver metastases&#xD;
      followed by a phase II study to determine the efficacy of such treatment on local control.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 22, 2012</start_date>
  <completion_date type="Anticipated">September 2033</completion_date>
  <primary_completion_date type="Anticipated">September 2028</primary_completion_date>
  <phase>N/A</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>Phase I of study: Number of participants with adverse events as a measure of safety and tolerability</measure>
    <time_frame>The major analysis for reporting the initial results of treatment will be undertaken when each patient has been potentially followed for a minimum of 3 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase II -local control within irradiated fields at 2 years</measure>
    <time_frame>The major analysis for reporting the initial results of treatment will be undertaken when each patient has been potentially followed for a minimum of 3 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">35</enrollment>
  <condition>Liver Metastases</condition>
  <arm_group>
    <arm_group_label>Proton Radiation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Proton</intervention_name>
    <description>All patients will receive 3 fractions in no more than 14 days at the following levels: Level I = 12 Gy per fraction, total dose=36 Gy.&#xD;
Level II = 16 Gy per fraction, total dose 48 Gy. Level III = 20 Gy per fraction, total dose 60 Gy. The dose per fraction to the PTV will start at dose level I (12 Gy), but may vary from 12 Gy to 20 Gy in 3 fractions over 14 days in 4 Gy increments</description>
    <arm_group_label>Proton Radiation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Proton Radiation</intervention_name>
    <arm_group_label>Proton Radiation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Pathologically confirmed non-lymphoma liver metastases or&#xD;
&#xD;
        New radiographic liver lesions consistent with metastases in patients with known&#xD;
        pathologically confirmed non-lymphoma cancer&#xD;
&#xD;
        1-3 liver lesions measurable on CT/MRI or PET/CT performed within 6 weeks prior to study&#xD;
        entry&#xD;
&#xD;
        Liver metastases measuring &lt;5cm&#xD;
&#xD;
        Life expectancy &gt;6 months&#xD;
&#xD;
        Disease outside the liver is allowed&#xD;
&#xD;
        Age ≥ 18&#xD;
&#xD;
        ECOG Performance Scale = 0-1&#xD;
&#xD;
        Adequate bone marrow function, defined as follows:&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 based upon CBC/differential obtained&#xD;
             within 4 weeks prior to registration on study&#xD;
&#xD;
          -  Platelets ≥ 60,000 cell/mm3 based upon CBC/differential obtained within 4 weeks prior&#xD;
             to registration on study&#xD;
&#xD;
          -  Hemoglobin ≥ 8.0 g/dl based upon CBC/differential obtained within 4 weeks prior to&#xD;
             registration on study (Note: the use of transfusion or other intervention to achieve&#xD;
             Hgb ≥ 8.0 is acceptable.)&#xD;
&#xD;
        Adequate kidney function (serum creatinine &lt;2mg/dL) based on chemistry panel obtained&#xD;
        within 4 weeks prior to registration on study&#xD;
&#xD;
        Adequate liver function, defined as total bilirubin &lt;5 mg/dL, serum albumin &gt;2.0g/dL, serum&#xD;
        levels of liver enzymes &lt; 5 times the upper limit of normal, and INR &lt; 1.5&#xD;
&#xD;
        Previous liver resection or ablative therapy is permitted&#xD;
&#xD;
        Chemotherapy and/or targeted agent therapy must be completed at least 2 weeks prior to&#xD;
        radiation and started at least 14 days after completion of SBPT Women of childbearing&#xD;
        potential and male participants must practice adequate contraception&#xD;
&#xD;
        Patient must sign study specific informed consent prior to study entry&#xD;
&#xD;
        Pretreatment evaluations required for eligibility include:&#xD;
&#xD;
          -  A complete history and general physical examination&#xD;
&#xD;
          -  For women of childbearing potential, a serum or urine pregnancy test must be performed&#xD;
             within 72 hours prior to registration&#xD;
&#xD;
          -  INR, total bilirubin, albumin, alkaline phosphatase, ALT, AST within 4 weeks prior to&#xD;
             study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Prior invasive malignancy other than liver met primary (except non-melanomatous skin&#xD;
        cancer) unless disease free for &gt; 3years&#xD;
&#xD;
        Prior radiotherapy that would results in overlap of radiation fields&#xD;
&#xD;
        Prior radiotherapy to the liver&#xD;
&#xD;
        Severe, active co-morbidity that may impact survival&#xD;
&#xD;
        CNS metastases&#xD;
&#xD;
        Tense ascites requiring frequent paracentesis&#xD;
&#xD;
        Active liver infection&#xD;
&#xD;
        Pregnancy, nursing women, or women of child bearing potential, and men who are sexually&#xD;
        active and not willing/able to use medically acceptable forms of contraception&#xD;
&#xD;
        Metastases location within 2cm of GI tract&#xD;
&#xD;
        -&#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>Gary Yang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>gyang@llu.edu</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Miriam Hernandez, RN</last_name>
    <phone>909-558-4000*; 909-558-4107</phone>
    <phone_ext>55240*</phone_ext>
    <email>mvhernandez@llu.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Gary Yang, MD</last_name>
    <phone>Backup: Sandi Teichman, RN</phone>
    <email>scteichm@llu.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Loma Linda University Medical Center</name>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <zip>92354</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Gary Yang, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Kang JI, Sufficool DC, Hsueh CT, Wroe AJ, Patyal B, Reeves ME, Slater JD, Yang GY. A phase I trial of Proton stereotactic body radiation therapy for liver metastases. J Gastrointest Oncol. 2019 Feb;10(1):112-117. doi: 10.21037/jgo.2018.08.17.</citation>
    <PMID>30788166</PMID>
  </results_reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>September 7, 2012</study_first_submitted>
  <study_first_submitted_qc>September 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <last_update_submitted>February 20, 2023</last_update_submitted>
  <last_update_submitted_qc>February 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Loma Linda University</investigator_affiliation>
    <investigator_full_name>Gary Yang, MD</investigator_full_name>
    <investigator_title>Radiation Oncologist, MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Liver Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT01697371
org study id: 5120022
nct id: NCT01697371
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
Local control of hepatic metastases appears to be a major determinant of overall survival.
      However, many patients are not suitable for resection due to medical or surgical reasons.
      Therefore, there is an important role for a treatment that can provide the equivalent of
      tumor resection with minimal morbidity. Stereotactic body radiotherapy (SBRT) delivers an
      ablative regimen of highly focused external beam radiotherapy that targets one or more
      discrete extracranial lesions. Published reports using SBRT to treat liver metastases have
      shown actuarial local control rates ranging from 50-100% with higher doses associated with
      better local control.

      In patients with metastatic liver disease, aggressive local therapy using modern radiotherapy
      techniques are promising and project to have a substantial role in the treatment of
      metastatic liver cancer to treat unresectable disease. The dosimetric advantage of proton
      therapy may lead to improved clinical outcomes with less morbidity, however, there is no
      clinical data to confirm this assertion. We thus propose a phase I study to determine the
      feasibility and safety of stereotactic body proton therapy in patients with liver metastases
      followed by a phase II study to determine the efficacy of such treatment on local control.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase I of study: Number of participants with adverse events as a measure of safety and tolerability
time frame: The major analysis for reporting the initial results of treatment will be undertaken when each patient has been potentially followed for a minimum of 3 months
measure: Phase II -local control within irradiated fields at 2 years
time frame: The major analysis for reporting the initial results of treatment will be undertaken when each patient has been potentially followed for a minimum of 3 months
arm group label: Proton Radiation
arm group type: Experimental
intervention type: Radiation
intervention name: Proton
description: All patients will receive 3 fractions in no more than 14 days at the following levels: Level I = 12 Gy per fraction, total dose=36 Gy.
Level II = 16 Gy per fraction, total dose 48 Gy. Level III = 20 Gy per fraction, total dose 60 Gy. The dose per fraction to the PTV will start at dose level I (12 Gy), but may vary from 12 Gy to 20 Gy in 3 fractions over 14 days in 4 Gy increments
arm group label: Proton Radiation
intervention type: Radiation
intervention name: Proton Radiation
arm group label: Proton Radiation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gary Yang, MD
role: Principal Investigator
affiliation: gyang@llu.edu
last name: Miriam Hernandez, RN
phone: 909-558-4000*; 909-558-4107
phone ext: 55240*
email: mvhernandez@llu.edu
last name: Gary Yang, MD
phone: Backup: Sandi Teichman, RN
email: scteichm@llu.edu
facility: 
status: Recruiting
investigator: 
country: United States
citation: Kang JI, Sufficool DC, Hsueh CT, Wroe AJ, Patyal B, Reeves ME, Slater JD, Yang GY. A phase I trial of Proton stereotactic body radiation therapy for liver metastases. J Gastrointest Oncol. 2019 Feb;10(1):112-117. doi: 10.21037/jgo.2018.08.17.
PMID: 30788166
responsible party type: Principal Investigator
investigator affiliation: Loma Linda University
investigator full name: Gary Yang, MD
investigator title: Radiation Oncologist, MD
mesh term: Neoplasm Metastasis
mesh term: Liver Neoplasms
sharing ipd: No