<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/NCT03808662</url>
  </required_header>
  <id_info>
    <org_study_id>18-431</org_study_id>
    <nct_id>NCT03808662</nct_id>
  </id_info>
  <brief_title>Randomized Study of Stereotactic Body Radiation Therapy (SBRT) in Patients With Oligoprogressive Metastatic Cancers of the Breast and Lung</brief_title>
  <official_title>Precision Radiation for OligoMetastatIc and MetaStatic DiseasE (PROMISE)-004: Consolidative Use of Radiotherapy to Block (CURB) Oligoprogression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is determine if receiving stereotactic body radiation(SBRT) when&#xD;
      participants' metastatic tumors have just begun to grow increase the length of time before&#xD;
      disease gets worse&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 16, 2019</start_date>
  <completion_date type="Anticipated">January 2024</completion_date>
  <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>Up to 52 weeks after final participant is enrolled</time_frame>
    <description>To study if the addition of early SBRT to extra-cranial oligo-progressive metastatic disease could prolong PFS compared to no SBRT. PFS is defined as the time from randomization to disease progression or death.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">107</enrollment>
  <condition>TNBC - Triple-Negative Breast Cancer</condition>
  <condition>Triple Negative Breast Cancer</condition>
  <condition>NSCLC</condition>
  <condition>NSCLC Stage IV</condition>
  <condition>Non Small Cell Lung Cancer</condition>
  <condition>Non Small Cell Lung Cancer Metastatic</condition>
  <condition>NSCLC Stage IV Without EGFR/ALK Mutation</condition>
  <arm_group>
    <arm_group_label>Arm 1: Early Stereotactic Body Radiotherapy/SBRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SBRT to all oligoprogressive sites</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2:Standard of Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Sterotactic Body Radiotherapy/SBRT</intervention_name>
    <description>In general, it is recommended using 9-10 Gy x 3 or 10 Gy x 5 fractions given every other day. Physicians should try to give the highest BED whenever possible while respecting normal tissue tolerance. All lesions are recommended to receive a biologically effective dose (BED) of 60 Gy or higher (BED10≥70), assuming α/β ratio of 10 and using the linear-quadratic model: BED = nd x [1 + d/(α/β)] where n is number of fractions and d is dose per fraction. Sometimes BED ≥80 Gy is preferred, with lower doses ≥50 Gy allowed at the discretion of the treating physician for concerns about normal tissue toxicity.</description>
    <arm_group_label>Arm 1: Early Stereotactic Body Radiotherapy/SBRT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of care</intervention_name>
    <description>Standard of care per physician discretion</description>
    <arm_group_label>Arm 2:Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 or older&#xD;
&#xD;
          -  Willing and able to provide informed consent&#xD;
&#xD;
          -  Metastatic disease detected on imaging and histologically confirmed:&#xD;
&#xD;
        Triple negative breast cancer TNBC (ER &lt;1%, PR &lt;1%, her-2-neu 0- 1+ by IHC or FISH-negative&#xD;
        or as determined by MD discretion)&#xD;
&#xD;
        OR NSCLC (without known EGFR mutation or ALK/ROS1 rearrangement)&#xD;
&#xD;
        OR Other high-risk breast cancer (per physician's discretion) progressed on hormone or&#xD;
        systemic therapy, regardless of ER/HER2 status&#xD;
&#xD;
        OR NSCLC with EGFR, ALK, or ROS1 targetable molecular alterations with disease progression&#xD;
        on first-line tyrosine kinase inhibitor&#xD;
&#xD;
        Note:&#xD;
&#xD;
          -  Biopsy of metastasis prior to enrollment is per treating physician's discretion per&#xD;
             standard of care. It is preferred but not required.&#xD;
&#xD;
          -  These patients are selected for the study given the similar survival outcomes when&#xD;
             given standard of care therapies&#xD;
&#xD;
          -  Patient has received at least first-line prior treatment with systemic therapy (either&#xD;
             cytotoxic or targeted, including maintenance therapies).&#xD;
&#xD;
          -  Patients who received prior immunotherapy are allowed.&#xD;
&#xD;
          -  Patients who had any prior radiation therapy near or overlapping with the&#xD;
             oligoprogressive sites are allowed to enroll.&#xD;
&#xD;
          -  Patients with the following medical conditions precluding them from participating in&#xD;
             other systemic therapy or drug trials are allowed:&#xD;
&#xD;
          -  active liver disease, including viral or other hepatitis, or cirrhosis&#xD;
&#xD;
          -  any other significant medical condition not under control, including any acute&#xD;
             coronary syndrome within the past 6 months.&#xD;
&#xD;
          -  a permanent pacemaker&#xD;
&#xD;
          -  a QTc &gt; 480 ms in the baseline EKG&#xD;
&#xD;
          -  peripheral neuropathy of grade &gt;/= 2 per NCI CTCAE&#xD;
&#xD;
          -  history or known autoimmune disease&#xD;
&#xD;
          -  current chronic systemic steroid therapy or any immunosuppressive therapy&#xD;
&#xD;
          -  history of primary immunodeficiency or solid organ transplant&#xD;
&#xD;
          -  known positive human immunodeficiency virus (HIV), chronic or active hepatitis B or C,&#xD;
             or active hepatitis A&#xD;
&#xD;
          -  active infection requiring systemic antibiotic therapy&#xD;
&#xD;
          -  Patients can have more than 5 metastases but can only have 1-5 oligo-progressive&#xD;
             lesions.&#xD;
&#xD;
          -  Oligoprogression, defined as Response Evaluation Criteria in Solid Tumors (RECIST) or&#xD;
             Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) documented&#xD;
             progression in up to 5 individual lesions&#xD;
&#xD;
        Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria as a guide:&#xD;
&#xD;
          1. At least a 20% increase in the sum of the longest diameter (LD) of the lesion, taking&#xD;
             as reference the smallest sum LD recorded since the last imaging OR&#xD;
&#xD;
          2. The appearance of one or more new lesions OR&#xD;
&#xD;
          3. New/malignant FDG uptake in the absence of other indications of progressive disease or&#xD;
             an anatomically stable lesion OR&#xD;
&#xD;
          4. &gt;/= 5mm increase in the diameter sum of the lesion&#xD;
&#xD;
        OR&#xD;
&#xD;
        Using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) as a guide:&#xD;
&#xD;
          1. &gt;30% increase in 18F-FDG SUV peak, with &gt;0.8 SUV units increase in tumor SUV from the&#xD;
             baseline scan in pattern typical of tumor and not of infection/treatment effect OR&#xD;
&#xD;
          2. Visible increase in the extent of 18F-FDG tumor uptake OR&#xD;
&#xD;
          3. New 18F-FDG avid lesions typical of cancer (including new bone lesion) and not related&#xD;
             to treatment effect and/or infection&#xD;
&#xD;
        OR&#xD;
&#xD;
        Development of a new soft tissue metastatic lesion at least 5mm in size or any new bone&#xD;
        metastasis&#xD;
&#xD;
        OR&#xD;
&#xD;
        Progressive enlargement of a known metastasis on 2 consecutive imaging studies at least 2&#xD;
        months apart with a minimum 5mm increase in size&#xD;
&#xD;
          -  All sites of oligoprogression can be safely treated&#xD;
&#xD;
          -  Maximum 5 progressing metastases in any single extra-cranial organ system (i.e. lung,&#xD;
             liver, bone)&#xD;
&#xD;
             a. If the clinical scenario deem that other forms of local therapy may be more&#xD;
             suitable for the metastatic disease, such as surgical resection and interventional&#xD;
             radiology-guided ablation, patients would be able to undergo other forms of local&#xD;
             therapy with discussion with the PI&#xD;
&#xD;
          -  No restriction on the total number of metastases&#xD;
&#xD;
          -  Note: If the clinical scenario deem that other forms of local therapy may be more&#xD;
             suitable for the metastatic disease, such as surgical resection and interventional&#xD;
             radiology-guided ablation, patients would be able to undergo other forms of local&#xD;
             therapy with discussion with the PI.&#xD;
&#xD;
          -  For patients with brain metastases and oligoprogression elsewhere where stereotactic&#xD;
             radiation to the brain is warranted, the brain lesions can be treated prior to&#xD;
             randomization. This will not be counted toward the 5 progressive lesions.&#xD;
&#xD;
          -  Any symptomatic metastatic sites requiring prompt palliative radiation (e.g. cord&#xD;
             compression) can also be treated with standard of care radiation prior to&#xD;
             randomization. This will not be counted toward the 5 progressive lesions.&#xD;
&#xD;
               1. If the clinical scenario deem that other forms of local therapy may be more&#xD;
                  suitable for the metastatic disease, such as surgical resection and&#xD;
                  interventional radiology-guided ablation, patients would be able to undergo other&#xD;
                  forms of local therapy with discussion with the PI.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Leptomeningeal disease.&#xD;
&#xD;
          -  Serious medical comorbidities precluding radiotherapy, such as ataxia-telangiectasia&#xD;
             or scleroderma.&#xD;
&#xD;
          -  Any other condition which in the judgment of the investigator would make the patient&#xD;
             inappropriate for entry into this study.&#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>Nadeem Riaz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Basking Ridge</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Commack</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Rockville Centre</name>
      <address>
        <city>Rockville Centre</city>
        <state>New York</state>
        <zip>11570</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Nassau</name>
      <address>
        <city>Uniondale</city>
        <state>New York</state>
        <zip>11553</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fred Hutchinson Cancer Research Center (Data Analysis Only)</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Hospital/Ontario Cancer Institute (Data Analysis Only)</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 17, 2019</study_first_posted>
  <last_update_submitted>June 29, 2023</last_update_submitted>
  <last_update_submitted_qc>June 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SBRT</keyword>
  <keyword>Stereotactic Body Radiotherapy</keyword>
  <keyword>Non-hematology metatstatic cancer</keyword>
  <keyword>non-CNS oligo-progressive disease</keyword>
  <keyword>intracranial metastatic disease</keyword>
  <keyword>Memorial Sloan Kettering Cancer Center</keyword>
  <keyword>18-431</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>• Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made following one year after publication and for up to 36 months later. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</ipd_description>
  </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/NCT03808662
org study id: 18-431
nct id: NCT03808662
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is determine if receiving stereotactic body radiation(SBRT) when
      participants' metastatic tumors have just begun to grow increase the length of time before
      disease gets worse
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival
time frame: Up to 52 weeks after final participant is enrolled
description: To study if the addition of early SBRT to extra-cranial oligo-progressive metastatic disease could prolong PFS compared to no SBRT. PFS is defined as the time from randomization to disease progression or death.
measure: Overall survival
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
arm group label: Arm 1: Early Stereotactic Body Radiotherapy/SBRT
arm group type: Experimental
description: SBRT to all oligoprogressive sites
arm group label: Arm 2:Standard of Care
arm group type: Active Comparator
intervention type: Radiation
intervention name: Sterotactic Body Radiotherapy/SBRT
description: In general, it is recommended using 9-10 Gy x 3 or 10 Gy x 5 fractions given every other day. Physicians should try to give the highest BED whenever possible while respecting normal tissue tolerance. All lesions are recommended to receive a biologically effective dose (BED) of 60 Gy or higher (BED10≥70), assuming α/β ratio of 10 and using the linear-quadratic model: BED = nd x [1 + d/(α/β)] where n is number of fractions and d is dose per fraction. Sometimes BED ≥80 Gy is preferred, with lower doses ≥50 Gy allowed at the discretion of the treating physician for concerns about normal tissue toxicity.
arm group label: Arm 1: Early Stereotactic Body Radiotherapy/SBRT
intervention type: Drug
intervention name: Standard of care
description: Standard of care per physician discretion
arm group label: Arm 2:Standard of Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nadeem Riaz, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
url: http://www.mskcc.org
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Triple Negative Breast Neoplasms
sharing ipd: Yes
ipd description: • Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made following one year after publication and for up to 36 months later. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.