xml: <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/NCT06004336</url>
    </required_header>
    <id_info>
      <org_study_id>2023-0006</org_study_id>
      <secondary_id>NCI-2023-06314</secondary_id>
      <nct_id>NCT06004336</nct_id>
    </id_info>
    <brief_title>A Randomized Trial of Maintenance Systemic Therapy After Radiation for Oligometastatic Renal Cell Carcinoma (ASTROs)</brief_title>
    <official_title>A Randomized Trial of Maintenance Systemic Therapy After Radiation for Oligometastatic Renal Cell Carcinoma (ASTROs)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>M.D. Anderson Cancer Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Merck Sharp &amp; Dohme LLC</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Cancer Prevention Research Institute of Texas</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>M.D. Anderson Cancer Center</source>
    <oversight_info>
      <has_dmc>Yes</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>
        To learn if adding 1 year of therapy with pembrolizumab can help to continue to control RCC&#xD;
        after radiation therapy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Primary Objectives:&#xD;
  &#xD;
          -  To evaluate PFS in patients randomized to definitive RT followed by pembrolizumab versus&#xD;
             definitive RT followed by observation.&#xD;
  &#xD;
        Secondary Objectives:&#xD;
  &#xD;
        Secondary Objective #1:&#xD;
  &#xD;
          -  To evaluate overall survival (OS) in patients randomized to definitive RT followed by&#xD;
             maintenance pembrolizumab versus definitive RT followed by observation.&#xD;
  &#xD;
        Secondary Objective #2:&#xD;
  &#xD;
          -  To evaluate time to next line systemic therapy (defined as systemic therapy given after&#xD;
             pembrolizumab) in patients randomized to definitive RT followed by maintenance&#xD;
             pembrolizumab versus definitive RT followed by observation.&#xD;
  &#xD;
        Secondary Objective #3:&#xD;
  &#xD;
          -  To evaluate local recurrence free survival (LRFS) in patients randomized to definitive&#xD;
             RT followed by maintenance pembrolizumab versus definitive RT followed by observation.&#xD;
  &#xD;
        Secondary Objective #4:&#xD;
  &#xD;
          -  To evaluate distant recurrence free survival (DRFS) in patients randomized to definitive&#xD;
             RT followed by maintenance pembrolizumab versus definitive RT followed by observation.&#xD;
  &#xD;
        Secondary Objective #5:&#xD;
  &#xD;
          -  To evaluate estimate PFS2, LRFS2, and DRFS2 in patients who crossed over from one&#xD;
             randomization arm to the other arm.&#xD;
  &#xD;
        Secondary Objective #6:&#xD;
  &#xD;
          -  To evaluate frequency of adverse events (AEs) in patients randomized to definitive RT&#xD;
             followed by maintenance pembrolizumab versus definitive RT followed by observation.&#xD;
  &#xD;
        Exploratory Objectives:&#xD;
  &#xD;
        Exploratory Objective #1:&#xD;
  &#xD;
          -  To determine the association of translational biomarkers including peripheral blood&#xD;
             markers and tissue markers with patient outcomes.&#xD;
  &#xD;
        Exploratory Objective #2:&#xD;
  &#xD;
          -  To determine changes in translational biomarkers including peripheral blood markers and&#xD;
             tissue markers after receipt of definitive RT.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">January 1, 2029</completion_date>
    <primary_completion_date type="Anticipated">January 1, 2028</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>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Participant)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0</measure>
      <time_frame>through study completion; an average of 2 years.</time_frame>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">144</enrollment>
    <condition>Oligometastatic Renal Cell Carcinoma</condition>
    <arm_group>
      <arm_group_label>Radiation therapy (Control Arm)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will be asked to receive radiation therapy and be randomly assigned to receive pembrolizumab or not after that.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Radiation Therapy and Pembrolizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will be asked to receive radiation therapy and be randomly assigned to receive pembrolizumab or not after that.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pembrolizumab</intervention_name>
      <description>Given by vein (IV)</description>
      <arm_group_label>Radiation Therapy and Pembrolizumab</arm_group_label>
      <arm_group_label>Radiation therapy (Control Arm)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Radiation therapy</intervention_name>
      <description>Given by vein (IV)</description>
      <arm_group_label>Radiation Therapy and Pembrolizumab</arm_group_label>
      <arm_group_label>Radiation therapy (Control Arm)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          In order to be eligible for trial participation, patients must have:&#xD;
  &#xD;
            1. The participant (or legally acceptable representative if applicable) provides written&#xD;
               informed consent for the trial.&#xD;
  &#xD;
            2. Pathologically confirmed diagnosis of RCC with a clear cell component.&#xD;
  &#xD;
            3. Be willing and able to undergo biopsy of a lesion planned for definitive RT. If a&#xD;
               lesion amenable to SBRT was biopsied prior to enrollment, this material can be used in&#xD;
               lieu of a planned biopsy if the tissue is available for review at MD Anderson. a.&#xD;
               Patients may be allowed on this trial without a biopsy if they are deemed medically&#xD;
               unfit for biopsy or if the biopsy poses undue risk in the opinion of the treating&#xD;
               physician(s).&#xD;
  &#xD;
            4. Be ≥18 years of age on the day of signing informed consent.&#xD;
  &#xD;
            5. ECOG performance status 0-1.&#xD;
  &#xD;
          NOTE: If subject is unable to walk due to paralysis, but is mobile in a wheelchair, subject&#xD;
          is ambulatory for the purpose of assessing their performance status.&#xD;
  &#xD;
            1. Have measurable disease based on RECIST 1.1. Lesions situated in a previously&#xD;
               irradiated area are considered measurable if progression has been demonstrated in such&#xD;
               lesions.&#xD;
  &#xD;
            2. Oligometastatic RCC patients (≤5 metastatic lesions at the time of study entry). Per&#xD;
               the discretion of the treating clinicians, we will not count lung lesions &lt;1 cm short&#xD;
               axis and LNs &lt;1.5 cm short axis as these lesions are often equivocal.&#xD;
  &#xD;
            3. Demonstrate adequate organ function as defined in the table below, all screening labs&#xD;
               should be performed within 10 days prior to enrollment.&#xD;
  &#xD;
            4. At least one site, which in the opinion of the treating radiation oncologist, is&#xD;
               treatable with definitive RT and can be biopsied.&#xD;
  &#xD;
            5. Criteria for known Hepatitis B and C positive subjects. Hepatitis B and C screening&#xD;
               tests are not required unless:&#xD;
  &#xD;
                 -  Known history of HBV or HCV infection&#xD;
  &#xD;
                 -  As mandated by local health authority&#xD;
  &#xD;
            6. Hepatitis B positive subjects • Participants who are HBsAg positive are eligible if&#xD;
               they have received HBV antiviral therapy for at least 4 weeks and have undetectable&#xD;
               HBV viral load prior to randomization.&#xD;
  &#xD;
               • Participants should remain on anti-viral therapy throughout study intervention and&#xD;
               follow local guidelines for HBV anti-viral therapy post completion of study&#xD;
               intervention.&#xD;
  &#xD;
            7. Participants with history of HCV infection are eligible if HCV viral load is&#xD;
               undetectable at screening.&#xD;
  &#xD;
               • Participants must have completed curative anti-viral therapy at least 4 weeks prior&#xD;
               to randomization.&#xD;
  &#xD;
               Table Adequate Organ Function Laboratory Values System Laboratory Value&#xD;
               --Hematological --Absolute neutrophil count (ANC) ≥1500/µL --Platelets ≥100 000/µL&#xD;
               --Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La --Renal --Creatinine OR Measured or calculatedb&#xD;
               creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN&#xD;
               OR ≥30 mL/min for participant with creatinine levels &gt;1.5 × institutional ULN Hepatic&#xD;
               --Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total&#xD;
               bilirubin levels &gt;1.5 × ULN --AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for&#xD;
               participants with liver metastases) --Coagulation International normalized ratio (INR)&#xD;
               OR prothrombin time (PT) --Activated partial thromboplastin time (aPTT) ≤1.5 × ULN&#xD;
               unless participant is receiving anticoagulant therapy as long as PT or aPTT is within&#xD;
               therapeutic range of intended use of anticoagulants&#xD;
  &#xD;
               --ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase);&#xD;
  &#xD;
                 -  AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase);&#xD;
                    ----GFR=glomerular filtration rate; ULN=upper limit of normal.&#xD;
  &#xD;
               a Criteria must be met without erythropoietin dependency and without packed red blood&#xD;
               cell (pRBC) transfusion within last 2 weeks.&#xD;
  &#xD;
               b Creatinine clearance (CrCl) should be calculated per institutional standard. Note:&#xD;
               This table includes eligibility-defining laboratory value requirements for treatment;&#xD;
               laboratory value requirements should be adapted according to local regulations and&#xD;
               guidelines for the administration of specific chemotherapies.&#xD;
  &#xD;
               Exclusion Criteria:&#xD;
  &#xD;
               The patient must be excluded from participating in the trial based on the following&#xD;
               conditions:&#xD;
  &#xD;
            1. The patient must have received their last dose of systemic therapy ≥24 weeks prior to&#xD;
               initiation of their first dose of RT if this therapy included immunotherapy (e.g.&#xD;
               pembrolizumab, nivolumab, ipilimumab, etc.) or ≥4 weeks prior to initiation of the&#xD;
               first dose of radiation if this systemic therapy did not include immunotherapy.&#xD;
  &#xD;
            2. Immunocompromising conditions, as follows:&#xD;
  &#xD;
               - Known acute or chronic human immunodeficiency virus (HIV) infection&#xD;
  &#xD;
               - History of primary immunodeficiency&#xD;
  &#xD;
                 -  History of allogeneic tissue/solid organ transplant&#xD;
  &#xD;
                 -  Current or prior use of immunosuppressive medication within 7 days before the&#xD;
                    first dose of study treatment, except for topical, ocular, intranasal, and&#xD;
                    inhaled corticosteroids, or systemic corticosteroids at an equivalent dose ≤10 mg&#xD;
                    of prednisone daily.&#xD;
  &#xD;
            3. Has known psychiatric or substance abuse disorders that would interfere with&#xD;
               cooperation with the requirements of the trial as determined by the treating physician&#xD;
               and/or member of the study team.&#xD;
  &#xD;
            4. Patients with a prior history of grade 3 or worse immune-related adverse events&#xD;
               attributed to checkpoint inhibitors (PD-1, PD-L1, or CTLA-4), except endocrine adverse&#xD;
               events with appropriate hormone replacement.&#xD;
  &#xD;
            5. Has received a live vaccine or live-attenuated vaccine within 30 days before the first&#xD;
               dose of study intervention. Administration of killed vaccines is allowed.&#xD;
  &#xD;
            6. Per the opinion of the treating physician of study team has cognitive impairments such&#xD;
               that appropriate informed consent cannot be obtained or that he/she cannot participate&#xD;
               in required study activities.&#xD;
  &#xD;
          1. Diffuse metastatic processes including leptomeningeal disease, diffuse bone marrow&#xD;
          involvement, and peritoneal carcinomatous, which by the discretion of the treating&#xD;
          physician cannot be treated definitively.&#xD;
  &#xD;
          2. Is pregnant, breast feeding, or expecting to conceive within the projected duration of&#xD;
          the trial at the screening visit and at least one of the following conditions apply.&#xD;
  &#xD;
            -  Not a woman of childbearing potential (WOCBP) as defined in Appendix OR&#xD;
  &#xD;
            -  A WOCBP who agrees to follow the contraceptive guidance in Appendix during the&#xD;
               treatment period and for at least 120 days (corresponding to time needed to eliminate&#xD;
               any study treatment(s) (pembrolizumab and/or any active comparator/combination) plus&#xD;
               30 days (a menstruation cycle) after the last dose of study treatment.&#xD;
  &#xD;
               3. A WOCBP who has a positive urine pregnancy test within 72 hours prior to&#xD;
               enrollment. If the urine test is positive or cannot be confirmed as negative, a serum&#xD;
               pregnancy test will be required.&#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>Chad Tang, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>M.D. Anderson Cancer Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Chad Tang, MD</last_name>
      <phone>(713) 745-7179</phone>
      <email>ctang1@mdanderson.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>M D Anderson Cancer Center</name>
        <address>
          <city>Houston</city>
          <state>Texas</state>
          <zip>77030</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Chad Tang, MD</last_name>
        <phone>713-745-7179</phone>
        <email>ctang1@mdanderson.org</email>
      </contact>
      <investigator>
        <last_name>Chad Tang, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>http://www.mdanderson.org</url>
      <description>M D Anderson Cancer Center</description>
    </link>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 15, 2023</study_first_submitted>
    <study_first_submitted_qc>August 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 21, 2023</last_update_submitted>
    <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 22, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </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>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pembrolizumab</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06004336
  org study id: 2023-0006
  secondary id: NCI-2023-06314
  nct id: NCT06004336
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  To learn if adding 1 year of therapy with pembrolizumab can help to continue to control RCC
        after radiation therapy.
  Primary Objectives:
  
          -  To evaluate PFS in patients randomized to definitive RT followed by pembrolizumab versus
             definitive RT followed by observation.
  
        Secondary Objectives:
  
        Secondary Objective #1:
  
          -  To evaluate overall survival (OS) in patients randomized to definitive RT followed by
             maintenance pembrolizumab versus definitive RT followed by observation.
  
        Secondary Objective #2:
  
          -  To evaluate time to next line systemic therapy (defined as systemic therapy given after
             pembrolizumab) in patients randomized to definitive RT followed by maintenance
             pembrolizumab versus definitive RT followed by observation.
  
        Secondary Objective #3:
  
          -  To evaluate local recurrence free survival (LRFS) in patients randomized to definitive
             RT followed by maintenance pembrolizumab versus definitive RT followed by observation.
  
        Secondary Objective #4:
  
          -  To evaluate distant recurrence free survival (DRFS) in patients randomized to definitive
             RT followed by maintenance pembrolizumab versus definitive RT followed by observation.
  
        Secondary Objective #5:
  
          -  To evaluate estimate PFS2, LRFS2, and DRFS2 in patients who crossed over from one
             randomization arm to the other arm.
  
        Secondary Objective #6:
  
          -  To evaluate frequency of adverse events (AEs) in patients randomized to definitive RT
             followed by maintenance pembrolizumab versus definitive RT followed by observation.
  
        Exploratory Objectives:
  
        Exploratory Objective #1:
  
          -  To determine the association of translational biomarkers including peripheral blood
             markers and tissue markers with patient outcomes.
  
        Exploratory Objective #2:
  
          -  To determine changes in translational biomarkers including peripheral blood markers and
             tissue markers after receipt of definitive RT.
  allocation: Randomized
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: Single (Participant)
  measure: Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
  time frame: through study completion; an average of 2 years.
  arm group label: Radiation therapy (Control Arm)
  arm group type: Experimental
  description: Participants will be asked to receive radiation therapy and be randomly assigned to receive pembrolizumab or not after that.
  arm group label: Radiation Therapy and Pembrolizumab
  arm group type: Experimental
  description: Participants will be asked to receive radiation therapy and be randomly assigned to receive pembrolizumab or not after that.
  intervention type: Drug
  intervention name: Pembrolizumab
  description: Given by vein (IV)
  arm group label: Radiation Therapy and Pembrolizumab
  arm group label: Radiation therapy (Control Arm)
  intervention type: Radiation
  intervention name: Radiation therapy
  description: Given by vein (IV)
  arm group label: Radiation Therapy and Pembrolizumab
  arm group label: Radiation therapy (Control Arm)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Chad Tang, MD
  role: Principal Investigator
  affiliation: M.D. Anderson Cancer Center
  last name: Chad Tang, MD
  phone: (713) 745-7179
  email: ctang1@mdanderson.org
  facility: 
  contact: 
  investigator: 
  country: United States
  url: http://www.mdanderson.org
  description: M D Anderson Cancer Center
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Carcinoma, Renal Cell
  mesh term: Pembrolizumab