<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/NCT02264548</url>
  </required_header>
  <id_info>
    <org_study_id>Renal Ablation</org_study_id>
    <nct_id>NCT02264548</nct_id>
  </id_info>
  <brief_title>A Phase I Evaluating Integration of HypofractionatedStudy Renal Ablative Radiotherapy</brief_title>
  <official_title>A Phase I Study Evaluating the Integration of Hypofractionated Renal Ablative Radiotherapy in the Setting of Metastatic Renal Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lawson Health Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lawson Health Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      -  evaluate the safety and toxicity profile of renal radio-ablation in the setting of&#xD;
           metastatic renal cell carcinoma.&#xD;
&#xD;
        -  to assess renal function post radio-ablation&#xD;
&#xD;
        -  Primary and metastatic tumour response to radio-ablation&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A dose limiting toxicity (DLT) will be defined as any grade 3, 4 or 5 toxicity event that is&#xD;
      considered to be definitely, probably or possibility related to the protocol radiation&#xD;
      therapy. Patients that cannot complete protocol therapy due to acute radiation side-effects&#xD;
      will also be considered to be a DLT. The general (non-exhausive) list of organ based toxicity&#xD;
      that could be related to this type of radiation therapy include toxicity to the liver,&#xD;
      kidney, bowel, spinal cord, and pancreas. Side-effects that are exclusively due to TKI&#xD;
      targeted therapy are not considered to be DLT in this protocol.&#xD;
&#xD;
      Three patients will be recruited for the first cohort of the trial. These patients will have&#xD;
      the PTV prescribed a dose of 25 Gray to be given in 5 daily fractions over a period of one&#xD;
      week (first treatment to start on a Wednesday or Thursday, with planned treatment on&#xD;
      successive business days). All therapy should be delivered within 10 business days including&#xD;
      any treatment breaks for acute toxicity. After 3 patients have been seen at the 4 week follow&#xD;
      up visit, CTCAE version three will be noted. If precisely 1 patient has a DLT, then an&#xD;
      additional 3 patients will be recruited to the same cohort and given the same treatment. If&#xD;
      no patient has DLT, then a new cohort of 3 patients will be treated to an increased dose of&#xD;
      30 Gray in 5 fractions. Similar criteria will dictate whether the trial ends, or continues&#xD;
      with the next cohort being treated to a dose of 35 Gray in 5 daily fractions. There will be a&#xD;
      maximum of 4 cohorts (25Gy, 30Gy, 35Gy, and 40Gy) in this study assuming no early DLT issues,&#xD;
      each containing 3 or 6 patients. Allowance for a -1 cohort arm of 20 Gy in 5 fractions is&#xD;
      made in this protocol for early DLT issues. The diagram below displays the schema in more&#xD;
      detail.&#xD;
&#xD;
      Any patient that does not complete protocol therapy due to toxicity issues or is unavailable&#xD;
      for the 4-week toxicity assessment is considered to be non-evaluable. These patients will&#xD;
      need to be replaced in terms of study accrual. Patients are not to be given TKI therapy&#xD;
      during the 4 week window post-RT in order to allow for proper evaluation of the RT&#xD;
      intervention; however, the treating oncologist ultimately can override this if it is in the&#xD;
      best medical interest of the patient (e.g. progressive and symptomatic systemic disease)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2009</start_date>
  <completion_date type="Actual">August 4, 2020</completion_date>
  <primary_completion_date type="Actual">August 4, 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>evaluate the safety/toxicity profile of renal radio-ablation in the setting of metastatic RCC</measure>
    <time_frame>After 3 patients have been seen at the 4 week follow up visit,</time_frame>
    <description>toxicity will be assessed using CTCAE v3</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Renal Function post renal radio-ablation</measure>
    <time_frame>4,8,12 wk and every 6months x 5yr</time_frame>
    <description>BUN, Creatinine</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Tumour Response</measure>
    <time_frame>4,8,12 wk and every 6 months x5yr.</time_frame>
    <description>CT abdomen evaluting primary disease using RECIST criteria</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Radiation: Radio-Ablation</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radio-Ablation</intervention_name>
    <description>Level I 20Gy/5 Level II 25Gy/5 Level III 30Gy/5 Level IV 35Gy/5 Level V 40Gy/5</description>
    <arm_group_label>Arm 1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Eligibility Criteria&#xD;
&#xD;
          -  Patients must have histologically confirmed carcinoma of the kidney&#xD;
&#xD;
          -  Patients must be able to tolerate extended treatment time 30 minutes for MVCT and&#xD;
             treatment delivery) for radiation on the tomotherapy unit&#xD;
&#xD;
          -  Patients must have confirmed metastatic disease, nodal or locally advanced disease&#xD;
             either by biopsy or imaging&#xD;
&#xD;
          -  Informed consent performed and documented&#xD;
&#xD;
          -  Patients must have one of a) unresectable local disease, b) be medically inoperable,&#xD;
             or c) chosen against having a local surgical treatment&#xD;
&#xD;
          -  Age ≥ 18&#xD;
&#xD;
          -  Patients previously received any targeted therapy or immunotherapy for RCC, are also&#xD;
             eligible. Patients must be off these agents for a minimum of 2 weeks prior to&#xD;
             radiation therapy to be eligible&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients without an adequate functioning contralateral kidney as seen on renal&#xD;
             perfusion scan (&gt;40% of total renal flow)&#xD;
&#xD;
          -  Patients with poor baseline renal function, represented by a creatinine clearance &lt; 50&#xD;
             mL/minute based on the Cockcroft-Gault approximation method&#xD;
&#xD;
          -  Patients with a creatinine clearance &lt; 50 ml/minute are still eligible if the&#xD;
             ipsilateral kidney has &lt;25% of the total renal flow on a renal perfusion scan.&#xD;
&#xD;
        еCCr =140 - (Age) × Mass (in kilograms) × constant Serum creatinine ( in µmol/L) constant =&#xD;
        male is 1.23, women is 1.04)&#xD;
&#xD;
          -  Previous abdominal radiotherapy&#xD;
&#xD;
          -  Bilateral RCC&#xD;
&#xD;
          -  Diagnosis of transitional cell carcinoma, squamous cell carcinoma, or a non epithelial&#xD;
             cancer of the kidney&#xD;
&#xD;
          -  Diagnosis of any other malignancy in previous 5 years, excluding non-melanoma skin&#xD;
             cancer -Known active malignancy other than RCC, excluding non-melanoma skin cancer&#xD;
&#xD;
          -  Estimated (by treating radiation oncologist) life expectancy of less than 8 weeks&#xD;
&#xD;
          -  Pregnant or breast-feeding women&#xD;
&#xD;
          -  Concurrent illness in addition to RCC that would make radiotherapy delivery unduly&#xD;
             challenging, including but not limited to, severe congestive heart failure or other&#xD;
             cardiorespiratory conditions, severe neuromuscular disorders, ongoing or active&#xD;
             infections, and psychiatric illness&#xD;
&#xD;
          -  Medical conditions for which radiation is contraindicated, including but not limited&#xD;
             to, scleroderma, systemic lupus erythematosus and ataxia teleangiectasia - Patients&#xD;
             with excessive kidney motion on pre-planning 4D-CT scan that would prevent safe&#xD;
             delivery of radiotherapy with gated or non-gated techniques&#xD;
&#xD;
          -  Patients taking concurrent medication that can interfere with the safe delivery of&#xD;
             radiation (e.g. radiosensitizers)&#xD;
&#xD;
          -  Urology opinion recommends partial nephrectomy as cytoreductive atment --Expected TKI&#xD;
             therapy to be initiated during initial 2 weeks completion of radiotherapy.&#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>Belal Ahmad, MD FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>London Regional Cancer Program of the Lawson Health Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>London Regional Cancer Program of the Laswon Research Health Institue</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Lawson Health Research Institute</investigator_affiliation>
    <investigator_full_name>Belal Ahmad</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
  </condition_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/NCT02264548
org study id: Renal Ablation
nct id: NCT02264548
lead sponsor: 
has dmc: Yes
-  evaluate the safety and toxicity profile of renal radio-ablation in the setting of
           metastatic renal cell carcinoma.

        -  to assess renal function post radio-ablation

        -  Primary and metastatic tumour response to radio-ablation
A dose limiting toxicity (DLT) will be defined as any grade 3, 4 or 5 toxicity event that is
      considered to be definitely, probably or possibility related to the protocol radiation
      therapy. Patients that cannot complete protocol therapy due to acute radiation side-effects
      will also be considered to be a DLT. The general (non-exhausive) list of organ based toxicity
      that could be related to this type of radiation therapy include toxicity to the liver,
      kidney, bowel, spinal cord, and pancreas. Side-effects that are exclusively due to TKI
      targeted therapy are not considered to be DLT in this protocol.

      Three patients will be recruited for the first cohort of the trial. These patients will have
      the PTV prescribed a dose of 25 Gray to be given in 5 daily fractions over a period of one
      week (first treatment to start on a Wednesday or Thursday, with planned treatment on
      successive business days). All therapy should be delivered within 10 business days including
      any treatment breaks for acute toxicity. After 3 patients have been seen at the 4 week follow
      up visit, CTCAE version three will be noted. If precisely 1 patient has a DLT, then an
      additional 3 patients will be recruited to the same cohort and given the same treatment. If
      no patient has DLT, then a new cohort of 3 patients will be treated to an increased dose of
      30 Gray in 5 fractions. Similar criteria will dictate whether the trial ends, or continues
      with the next cohort being treated to a dose of 35 Gray in 5 daily fractions. There will be a
      maximum of 4 cohorts (25Gy, 30Gy, 35Gy, and 40Gy) in this study assuming no early DLT issues,
      each containing 3 or 6 patients. Allowance for a -1 cohort arm of 20 Gy in 5 fractions is
      made in this protocol for early DLT issues. The diagram below displays the schema in more
      detail.

      Any patient that does not complete protocol therapy due to toxicity issues or is unavailable
      for the 4-week toxicity assessment is considered to be non-evaluable. These patients will
      need to be replaced in terms of study accrual. Patients are not to be given TKI therapy
      during the 4 week window post-RT in order to allow for proper evaluation of the RT
      intervention; however, the treating oncologist ultimately can override this if it is in the
      best medical interest of the patient (e.g. progressive and symptomatic systemic disease)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: evaluate the safety/toxicity profile of renal radio-ablation in the setting of metastatic RCC
time frame: After 3 patients have been seen at the 4 week follow up visit,
description: toxicity will be assessed using CTCAE v3
measure: Renal Function post renal radio-ablation
time frame: 4,8,12 wk and every 6months x 5yr
description: BUN, Creatinine
measure: Tumour Response
time frame: 4,8,12 wk and every 6 months x5yr.
description: CT abdomen evaluting primary disease using RECIST criteria
arm group label: Arm 1
arm group type: Experimental
description: Radiation: Radio-Ablation
intervention type: Radiation
intervention name: Radio-Ablation
description: Level I 20Gy/5 Level II 25Gy/5 Level III 30Gy/5 Level IV 35Gy/5 Level V 40Gy/5
arm group label: Arm 1
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Belal Ahmad, MD FRCPC
role: Principal Investigator
affiliation: London Regional Cancer Program of the Lawson Health Research Institute
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Lawson Health Research Institute
investigator full name: Belal Ahmad
investigator title: Principal Investigator
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell