<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/NCT03307538</url>
  </required_header>
  <id_info>
    <org_study_id>NL 60588.078.17</org_study_id>
    <nct_id>NCT03307538</nct_id>
  </id_info>
  <brief_title>Stereotactic Body Radiation Therapy for Unresectable Perihilar Cholangiocarcinoma</brief_title>
  <acronym>STRONG</acronym>
  <official_title>A Pilot Study to Determine the Feasibility of Stereotactic Body Radiation Therapy Following Chemotherapy for Unresectable Perihilar Cholangiocarcinoma. &quot;The STRONG Trial&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Erasmus Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Erasmus Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Rationale:&#xD;
&#xD;
      For patients with perihilar cholangiocarcinoma, surgery is the only treatment modality that&#xD;
      can result in cure. Unfortunately, in the majority of these patients the tumors are found to&#xD;
      be unresectable at presentation due to local invasive tumor growth or the presence of distal&#xD;
      metastases. For patients with unresectable cholangiocarcinoma palliative chemotherapy is the&#xD;
      standard treatment yielding an estimated median overall survival of 12-15.2 months. There is&#xD;
      no evidence from randomized trials that support the routine use of stereotactic body&#xD;
      radiation therapy (SBRT) for cholangiocarcinoma. However, small and most often retrospective&#xD;
      studies combining chemotherapy with SBRT showed promising results with overall survival&#xD;
      reaching up to 33-35 months.&#xD;
&#xD;
      Based upon these observations, the investigators designed a local feasibility trial with SBRT&#xD;
      after chemotherapy in patients with unresectable perihilar cholangiocarcinoma in order to try&#xD;
      to confirm the observed tolerability of adding SBRT to standard chemotherapy. The expected&#xD;
      time to include the required patients for this pilot study will be one year.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To assess feasibility of SBRT as add on treatment after standard chemotherapy.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      Local feasibility trial.&#xD;
&#xD;
      Study population:&#xD;
&#xD;
      Patients diagnosed with perihilar cholangiocarcinoma, 18 years of age or older, T1-4 N0-1 M0&#xD;
      (AJCC 7th Edition), after completion of standard chemotherapy. Exclusion criteria are local&#xD;
      tumor growth into either stomach, colon, duodenum, pancreas or abdominal wall. Sample size&#xD;
      will be 6 patients.&#xD;
&#xD;
      Intervention:&#xD;
&#xD;
      SBRT will be delivered in 15 fractions of 3 to 4.5Gy after 8 cycles of chemotherapy. In case&#xD;
      of toxicity causing premature termination of systemic treatment, the patient can still&#xD;
      proceed to SBRT.&#xD;
&#xD;
      Main study parameters/endpoints:&#xD;
&#xD;
      The primary endpoint of this study is feasibility measured by radiotherapy induced toxicity&#xD;
      according to CTC v4.0.3.&#xD;
&#xD;
      Secondary endpoints will be:&#xD;
&#xD;
        -  Quality of life&#xD;
&#xD;
        -  Local progression&#xD;
&#xD;
        -  Progression free survival&#xD;
&#xD;
        -  Overall survival&#xD;
&#xD;
        -  Cellular radiosensitivity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For patients with perihilar cholangiocarcinoma, surgery is the only treatment modality that&#xD;
      can result in cure. Unfortunately, in the majority of these patients the tumors are found to&#xD;
      be unresectable at presentation due to local invasive tumor growth or the presence of distant&#xD;
      metastases. For these patients palliative chemotherapy is the standard treatment yielding an&#xD;
      estimated median overall survival of 12-15.2 months. There is no evidence from randomized&#xD;
      trials that supports the routine use of stereotactic body radiation therapy (SBRT) for&#xD;
      unresectable cholangiocarcinoma. However, small and most often retrospective studies&#xD;
      combining chemotherapy with SBRT showed promising results with overall survival reaching up&#xD;
      to 33-35 months.&#xD;
&#xD;
      This pilot study is designed as a first step to confirm and extend these findings. Up to six&#xD;
      patients diagnosed with unresectable perihilar cholangiocarcinoma will be treated with&#xD;
      standard chemotherapy followed by SBRT in order to assess possible severe side effects of the&#xD;
      treatment. As part of this research, patients will be followed with CT- or MRI-scan and blood&#xD;
      tests exams until progression. In addition to this clinical evaluation, the investigators&#xD;
      will also work towards developing a predictive assay for radiotherapy response of both normal&#xD;
      and tumor tissue by establishing normal tissue and tumor organoids and determining several&#xD;
      key parameters for their response to ionizing radiation treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 6, 2017</start_date>
  <completion_date type="Actual">June 30, 2020</completion_date>
  <primary_completion_date type="Actual">March 30, 2020</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>Acute toxicity</measure>
    <time_frame>3 months</time_frame>
    <description>Limiting toxicity will be defined as more than one patient with grade 4 hepatobiliary toxicity related to study procedures, or more than one patient with grade 3 gastrointestinal toxicity related to study procedures, occurring in the period up to 3 months after the last SBRT administration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>2 years</time_frame>
    <description>Assessed by means of the EORTC QLQ-C30 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>2 years</time_frame>
    <description>Assessed by means of the EORTC QLQ-BIL21 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>2 years</time_frame>
    <description>Assessed by means of the EuroQoL-5D questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local progression</measure>
    <time_frame>2 years</time_frame>
    <description>Measured on CT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local progression</measure>
    <time_frame>2 years</time_frame>
    <description>Measured on MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>2 years</time_frame>
    <description>Time from treatment to progression measured on CT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cellular radiosensitivity</measure>
    <time_frame>2 years</time_frame>
    <description>A predictive assay will be developed for radiotherapy response of both normal and tumor tissue by establishing normal tissue and tumor organoids and determining several key parameters for their response to ionizing radiation treatment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Klatskin Tumor</condition>
  <arm_group>
    <arm_group_label>Stereotactic body radiation therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Stereotactic body radiation therapy</intervention_name>
    <description>15 fractions of 3-4,5 Gy (risk-adapted)</description>
    <arm_group_label>Stereotactic body radiation therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
        In order to be eligible to participate in this study, a subject must be discussed in a&#xD;
        multidisciplinary liver tumor board and should meet all of the following criteria:&#xD;
&#xD;
          -  Patients diagnosed with perihilar cholangiocarcinoma according to the criteria of the&#xD;
             Mayo Clinic, Rochester:&#xD;
&#xD;
               -  Positive or strongly suspicious intraluminal brush or biopsy or,&#xD;
&#xD;
               -  A radiographic malignant appearing stricture plus either:&#xD;
&#xD;
                    -  CA 19-9&gt;100 U/ml in the absence of acute bacterial cholangitis, or&#xD;
&#xD;
                    -  polysomy on FISH, or&#xD;
&#xD;
                    -  a well-defined mass on cross sectional imaging.&#xD;
&#xD;
          -  One tumor mass&#xD;
&#xD;
          -  Unresectable tumor&#xD;
&#xD;
          -  Finished chemotherapy treatment with Gemcitabine and Cisplatin, preferably 8 cycles.&#xD;
             If less cycles are given, patients are still eligible for this study.&#xD;
&#xD;
          -  T1-T4 (AJCC staging 7th edition), before chemotherapy&#xD;
&#xD;
          -  N0-N1 (AJCC staging 7th edition), radiologically or pathologically suspect, before&#xD;
             chemotherapy&#xD;
&#xD;
          -  Measurable disease to be selected as a target on CT/MRI-scan, according to RECIST&#xD;
             criteria, after chemotherapy within 6 weeks prior to inclusion&#xD;
&#xD;
          -  Tumor visibility on CT&#xD;
&#xD;
          -  If liver cirrhosis is present, it should be well compensated, with Child-Pugh grade A.&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  ECOG performance status 0-1&#xD;
&#xD;
          -  Bilirubin ≤1.5 times normal value, AST/ALT ≤5 times ULN, within 6 weeks prior to&#xD;
             inclusion&#xD;
&#xD;
          -  Platelets ≥ 50x10E9/ l, Leukocytes &gt; 1.5x10E9/l, Hb &gt; 6 mmol/l, within 6 weeks prior&#xD;
             to inclusion&#xD;
&#xD;
          -  Written informed consent, after chemotherapy&#xD;
&#xD;
          -  Willing and able to comply to the follow-up schedule&#xD;
&#xD;
          -  Able to start SBRT within 12 weeks after completion of chemotherapy.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Eligibility for resection&#xD;
&#xD;
          -  Prior surgery or transplantation&#xD;
&#xD;
          -  Multifocal tumor&#xD;
&#xD;
          -  Tumor extension in stomach, colon, duodenum, pancreas or abdominal wall.&#xD;
&#xD;
          -  N2, (AJCC staging 7th edition), radiologically or pathologically suspect, before&#xD;
             chemotherapy&#xD;
&#xD;
          -  Distant metastases&#xD;
&#xD;
          -  Progression (local or distant) during or after chemotherapy Ascites&#xD;
&#xD;
          -  Previous radiotherapy to the liver&#xD;
&#xD;
          -  Current pregnancy&#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>Alejandra Méndez Romero, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Erasmus Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Erasmus MC</name>
      <address>
        <city>Rotterdam</city>
        <state>Zuid Holland</state>
        <zip>3015 CE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>September 26, 2017</study_first_submitted>
  <study_first_submitted_qc>October 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>January 25, 2021</last_update_submitted>
  <last_update_submitted_qc>January 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Erasmus Medical Center</investigator_affiliation>
    <investigator_full_name>Alejandra Mendez Romero</investigator_full_name>
    <investigator_title>A. Méndez Romero MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Perihilar cholangiocarcinoma</keyword>
  <keyword>Klatskin tumor</keyword>
  <keyword>Stereotactic body radiation therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholangiocarcinoma</mesh_term>
    <mesh_term>Klatskin Tumor</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/NCT03307538
org study id: NL 60588.078.17
nct id: NCT03307538
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Rationale:

      For patients with perihilar cholangiocarcinoma, surgery is the only treatment modality that
      can result in cure. Unfortunately, in the majority of these patients the tumors are found to
      be unresectable at presentation due to local invasive tumor growth or the presence of distal
      metastases. For patients with unresectable cholangiocarcinoma palliative chemotherapy is the
      standard treatment yielding an estimated median overall survival of 12-15.2 months. There is
      no evidence from randomized trials that support the routine use of stereotactic body
      radiation therapy (SBRT) for cholangiocarcinoma. However, small and most often retrospective
      studies combining chemotherapy with SBRT showed promising results with overall survival
      reaching up to 33-35 months.

      Based upon these observations, the investigators designed a local feasibility trial with SBRT
      after chemotherapy in patients with unresectable perihilar cholangiocarcinoma in order to try
      to confirm the observed tolerability of adding SBRT to standard chemotherapy. The expected
      time to include the required patients for this pilot study will be one year.

      Objective:

      To assess feasibility of SBRT as add on treatment after standard chemotherapy.

      Study design:

      Local feasibility trial.

      Study population:

      Patients diagnosed with perihilar cholangiocarcinoma, 18 years of age or older, T1-4 N0-1 M0
      (AJCC 7th Edition), after completion of standard chemotherapy. Exclusion criteria are local
      tumor growth into either stomach, colon, duodenum, pancreas or abdominal wall. Sample size
      will be 6 patients.

      Intervention:

      SBRT will be delivered in 15 fractions of 3 to 4.5Gy after 8 cycles of chemotherapy. In case
      of toxicity causing premature termination of systemic treatment, the patient can still
      proceed to SBRT.

      Main study parameters/endpoints:

      The primary endpoint of this study is feasibility measured by radiotherapy induced toxicity
      according to CTC v4.0.3.

      Secondary endpoints will be:

        -  Quality of life

        -  Local progression

        -  Progression free survival

        -  Overall survival

        -  Cellular radiosensitivity.
For patients with perihilar cholangiocarcinoma, surgery is the only treatment modality that
      can result in cure. Unfortunately, in the majority of these patients the tumors are found to
      be unresectable at presentation due to local invasive tumor growth or the presence of distant
      metastases. For these patients palliative chemotherapy is the standard treatment yielding an
      estimated median overall survival of 12-15.2 months. There is no evidence from randomized
      trials that supports the routine use of stereotactic body radiation therapy (SBRT) for
      unresectable cholangiocarcinoma. However, small and most often retrospective studies
      combining chemotherapy with SBRT showed promising results with overall survival reaching up
      to 33-35 months.

      This pilot study is designed as a first step to confirm and extend these findings. Up to six
      patients diagnosed with unresectable perihilar cholangiocarcinoma will be treated with
      standard chemotherapy followed by SBRT in order to assess possible severe side effects of the
      treatment. As part of this research, patients will be followed with CT- or MRI-scan and blood
      tests exams until progression. In addition to this clinical evaluation, the investigators
      will also work towards developing a predictive assay for radiotherapy response of both normal
      and tumor tissue by establishing normal tissue and tumor organoids and determining several
      key parameters for their response to ionizing radiation treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Acute toxicity
time frame: 3 months
description: Limiting toxicity will be defined as more than one patient with grade 4 hepatobiliary toxicity related to study procedures, or more than one patient with grade 3 gastrointestinal toxicity related to study procedures, occurring in the period up to 3 months after the last SBRT administration.
measure: Quality of life
time frame: 2 years
description: Assessed by means of the EORTC QLQ-C30 questionnaire
measure: Quality of life
time frame: 2 years
description: Assessed by means of the EORTC QLQ-BIL21 questionnaire
measure: Quality of life
time frame: 2 years
description: Assessed by means of the EuroQoL-5D questionnaire
measure: Local progression
time frame: 2 years
description: Measured on CT
measure: Local progression
time frame: 2 years
description: Measured on MRI
measure: Progression free survival
time frame: 2 years
description: Time from treatment to progression measured on CT
measure: Overall survival
time frame: 2 years
measure: Cellular radiosensitivity
time frame: 2 years
description: A predictive assay will be developed for radiotherapy response of both normal and tumor tissue by establishing normal tissue and tumor organoids and determining several key parameters for their response to ionizing radiation treatment.
arm group label: Stereotactic body radiation therapy
arm group type: Experimental
intervention type: Radiation
intervention name: Stereotactic body radiation therapy
description: 15 fractions of 3-4,5 Gy (risk-adapted)
arm group label: Stereotactic body radiation therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alejandra Méndez Romero, MD, PhD
role: Principal Investigator
affiliation: Erasmus Medical Center
facility: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Erasmus Medical Center
investigator full name: Alejandra Mendez Romero
investigator title: A. Méndez Romero MD, PhD
mesh term: Cholangiocarcinoma
mesh term: Klatskin Tumor
sharing ipd: No