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/NCT06041503</url>
    </required_header>
    <id_info>
      <org_study_id>10001533</org_study_id>
      <secondary_id>001533-C</secondary_id>
      <nct_id>NCT06041503</nct_id>
    </id_info>
    <brief_title>Enfortumab Vedotin With or Without Pembrolizumab in Rare Genitourinary Tumors</brief_title>
    <official_title>A Phase II Multicenter Study of Enfortumab Vedotin With or Without Pembrolizumab in Rare Genitourinary Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Cancer Institute (NCI)</agency>
        <agency_class>NIH</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Institutes of Health Clinical Center (CC)</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>
        Background:&#xD;
  &#xD;
        Many cancers of the testicles and urinary tract are rare diseases; these are diseases that&#xD;
        affect less than 200,000 people in the United States. It can be hard to study treatments for&#xD;
        these diseases. One combination of drugs-enfortumab vedotin (EV) and pembrolizumab-has&#xD;
        already been approved to treat some urinary cancers. Researchers want to see if they can help&#xD;
        people with other types of testicle and urinary cancers.&#xD;
  &#xD;
        Objective:&#xD;
  &#xD;
        To test EV, with or without pembrolizumab, in patients with rarer cancers of the testicles or&#xD;
        urinary tract.&#xD;
  &#xD;
        Eligibility:&#xD;
  &#xD;
        People aged 18 and older with rarer cancers of the testicles or urinary tract.&#xD;
  &#xD;
        Design:&#xD;
  &#xD;
        Participants will be screened. They will have a physical exam with blood and urine tests.&#xD;
        Their ability to perform normal daily activities will be tested. They will have exams of&#xD;
        their skin and eyes. They will have imaging scans. A biopsy may be needed: A sample of tissue&#xD;
        will be removed from the tumor.&#xD;
  &#xD;
        The study drugs are both given through a tube attached to a needle inserted into a vein in&#xD;
        the arm. Some participants will receive treatments 3 times during 28-week cycles; others will&#xD;
        receive treatments 2 times during 21-day cycles.&#xD;
  &#xD;
        All participants may continue to receive treatments for up to 5 years. Imaging scans and&#xD;
        other tests will be repeated.&#xD;
  &#xD;
        Participants who stop taking the drugs will have follow-up visits every 3 to 4 weeks until&#xD;
        the disease gets worse. They will have imaging scans and blood tests.&#xD;
  &#xD;
        After that, follow-up visits will continue by phone every 3 months for up to 5 years after&#xD;
        study therapy is finished.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background:&#xD;
  &#xD;
          -  Rare genitourinary (GU) tumors are tumors of aberrant histology occurring in the GU&#xD;
             tract including kidney, bladder, ureters, testes, and penis. Due to their rarity, they&#xD;
             are not systematically captured by currently available registries, treatment protocols&#xD;
             or tissue banks.&#xD;
  &#xD;
          -  Large randomized clinical trials are logistically difficult in these small patient&#xD;
             populations. Therefore, treatment information is obtained from case reports,&#xD;
             retrospective studies, and small clinical trials, and is frequently extrapolated from&#xD;
             trials on similar tumor types.&#xD;
  &#xD;
          -  Pembrolizumab is a potent and highly selective humanized monoclonal antibody that&#xD;
             targets immune checkpoint programmed cell death protein 1 (PD-1) receptor.&#xD;
  &#xD;
          -  Nectin-4 is a type 1 transmembrane protein and member of a family of related&#xD;
             immunoglobulinlike adhesion molecules implicated in cell-cell adhesion.&#xD;
  &#xD;
          -  Nectin-4 is highly expressed in cancer cells, particularly in urothelial carcinomas&#xD;
             (UCs).&#xD;
  &#xD;
          -  Enfortumab vedotin (EV) is an antibody-drug conjugate consisting of a human monoclonal&#xD;
             antibody to nectin-4 and monomethyl auristatin E (MMAE), a microtubule disrupting&#xD;
             cytotoxic agent. EV has demonstrated a survival benefit in the setting of metastatic&#xD;
             urothelial carcinoma, which has almost universally high nectin-4 expression.&#xD;
  &#xD;
          -  There is data in UC and bladder cancer variants showing co-existence of nectin-4&#xD;
             expression and programmed cell death 1 ligand 1 (PD-L1) expression and mismatch repair&#xD;
             deficiency.&#xD;
  &#xD;
          -  There is currently very limited data on the level of nectin-4 expression in rare GU&#xD;
             tumors and no evidence for the activity of EV in these tumors.&#xD;
  &#xD;
        Objective:&#xD;
  &#xD;
        -To assess the objective response rate (ORR) per RECIST v 1.1 in participants with rare&#xD;
        genitourinary (GU) tumors treated with enfortumab vedotin (EV) with or without pembrolizumab.&#xD;
  &#xD;
        Eligibility:&#xD;
  &#xD;
          -  Age &gt;= 18 years&#xD;
  &#xD;
          -  Histologically confirmed diagnosis of locally advanced or metastatic pure adenocarcinoma&#xD;
             of the bladder, pure squamous cell carcinoma of the bladder, or treatment-refractory&#xD;
             testicular germ cell tumors.&#xD;
  &#xD;
          -  Participants may have received any number of prior anti-cancer treatments or be&#xD;
             treatment na(SqrRoot) ve (with the exception of participants with testicular germ cell&#xD;
             tumors, whom must have exhausted all standard curative-intent options).&#xD;
  &#xD;
        Design:&#xD;
  &#xD;
          -  This multisite study is a phase II, open label, multicohort, nonrandomized study with&#xD;
             two arms.&#xD;
  &#xD;
          -  Participants with:&#xD;
  &#xD;
               -  Adenocarcinoma of the bladder will be enrolled in Cohort A (Cohort A1: prior&#xD;
                  anti-1/PD-L1 therapy; Cohort A2: no prior anti-PD-1/PD-L1 therapy).&#xD;
  &#xD;
               -  Squamous cell carcinoma of the bladder will be enrolled in Cohort B (Cohort B1:&#xD;
                  prior anti-PD-1/PD-L1 therapy; Cohort B2: no prior anti-PD-1/PD-L1 therapy).&#xD;
  &#xD;
               -  Testicular germ cell tumors will be enrolled in Cohort C (Cohort C1: prior&#xD;
                  anti-PD-1/PDL1 therapy; Cohort C2: no prior anti-PD-1/PD-L1 therapy).&#xD;
  &#xD;
          -  All participants will receive EV.&#xD;
  &#xD;
          -  Participants without prior immune checkpoint inhibitor (ICI) exposure will be eligible&#xD;
             to receive concurrent pembrolizumab.&#xD;
  &#xD;
          -  Arm 1: EV monotherapy will be given in 28-day cycles for a maximum of 5 years, or until&#xD;
             disease progression or intolerable side effects. EV will be administered I.V. at 1.25&#xD;
             mg/kg on days 1, 8, and 15 of each cycle.&#xD;
  &#xD;
          -  Arm 2: EV and pembrolizumab will be given in 21-day cycles. EV will be administered I.V.&#xD;
             at 1.25 mg/kg on days 1 and 8 of each cycle. Pembrolizumab will be administered I.V. at&#xD;
             200 mg on day 1.&#xD;
  &#xD;
               -  EV and pembrolizumab will be given for 35 cycles, or until a confirmed complete&#xD;
                  response, disease progression or intolerable side effects.&#xD;
  &#xD;
               -  After the 35th cycle, EV may be continued to be given for a maximum of 5 years, or&#xD;
                  until disease progression or intolerable side effects.&#xD;
  &#xD;
               -  Participants who have completed 35 cycles of pembrolizumab or stopped pembrolizumab&#xD;
                  for confirmed complete response may be eligible for up to additional 17 cycles of&#xD;
                  pembrolizumab if there is investigator-determined progressive disease by RECIST 1.1&#xD;
                  after initial treatment.&#xD;
  &#xD;
          -  The accrual ceiling will be set at 68 participants to allow for inevaluable&#xD;
             participants.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 21, 2023</start_date>
    <completion_date type="Anticipated">October 1, 2028</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2027</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Objective response rate (ORR)</measure>
      <time_frame>At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD</time_frame>
      <description>Percentage of participants by best overall response (e.g., CR, PR, SD, PD) to therapy</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Second Objective response rate (ORR2) and second progression-free survival (PFS2) after second course of pembrolizumab</measure>
      <time_frame>At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD</time_frame>
      <description>Percentage of participants with the best overall response of CR or PR to therapy and duration of time from start of treatment to time of progression or death, whichever occurs first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of response (DoR)</measure>
      <time_frame>At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD</time_frame>
      <description>Time from start of treatment to disease progression or death in participants who achieve CR or PR</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>Day 1 of each cycle, at EoT, at the Safety visits, and every 90 days for up to a total of 5 years after the end of therapy.</time_frame>
      <description>Time from the start of treatment that participants are still alive.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD</time_frame>
      <description>Duration of time from start of treatment to time of progression or death, whichever occurs first</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical benefit rate (CBR)</measure>
      <time_frame>At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD</time_frame>
      <description>Percentage of participant who have achieved CR, PR, and SD while on treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety of EV with or without pembrolizumab</measure>
      <time_frame>From first dose through 30 days after last treatment with EV and 90 days after last treatment with pembrolizumab</time_frame>
      <description>Adverse events (AEs) will be reported by type and grade of toxicity</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">68</enrollment>
    <condition>Adenocarcinoma of the Bladder</condition>
    <condition>Squamous Cell Carcinoma of the Bladder</condition>
    <condition>Testicular Germ Cell Tumors</condition>
    <arm_group>
      <arm_group_label>Arm 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Treatment with enfortumab vedotin</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Treatment with enfortumab vedotin and pembrolizumab</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Enfortumab vedotin</intervention_name>
      <description>EV is administered IV at 1.25 mg/kg on days 1, 8, and 15 of each 28-day cycle or on days 1 and 8 of each 21-day cycle.</description>
      <arm_group_label>Arm 1</arm_group_label>
      <arm_group_label>Arm 2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pembrolizumab</intervention_name>
      <description>Pembrolizumab is administered IV at 200 mg on day 1 of each 21-day cycle.</description>
      <arm_group_label>Arm 2</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          -  INCLUSION CRITERIA:&#xD;
  &#xD;
            -  Participants must have histologically confirmed locally advanced or metastatic pure&#xD;
               adenocarcinoma of the bladder, pure squamous cell carcinoma of the bladder, or&#xD;
               treatment-refractory testicular germ cell tumors.&#xD;
  &#xD;
            -  Participants must have measurable disease, per RECIST 1.1.&#xD;
  &#xD;
            -  Participants must have locally advanced or metastatic disease defined as new or&#xD;
               progressive lesions on cross sectional imaging.&#xD;
  &#xD;
            -  Participants in Cohorts A1, B1, and C1 must have received prior anti-PD-1/PD-L1&#xD;
               therapy in any setting.&#xD;
  &#xD;
            -  Participants in Cohorts A2, B2, and C2 must be immune checkpoint inhibitor naive.&#xD;
  &#xD;
            -  Participants may be systemic treatment naive except for participants with testicular&#xD;
               germ cell tumors, whom must have received and be refractory to all standard options of&#xD;
               curative-intent treatment.&#xD;
  &#xD;
            -  Age &gt;= 18 years.&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status &lt;= 1 (Karnofsky &gt;= 70%)&#xD;
  &#xD;
            -  Participants must have adequate organ and marrow function as defined below:&#xD;
  &#xD;
                 -  Hemoglobin &gt;= 9g/dL&#xD;
  &#xD;
                 -  Absolute neutrophil count (ANC) &gt;= 1,500/mcL&#xD;
  &#xD;
                 -  Platelets &gt;= 100,000/mcL&#xD;
  &#xD;
                 -  Total bilirubin &lt;= 1.5 x upper limit of normal (ULN) (&lt;= 3 x ULN in participants&#xD;
                    with known/suspected Gilbert s disease)&#xD;
  &#xD;
                 -  AST(SGOT/ALT(SGPT) &lt;= 2.5 X institutional upper limit of normal (ULN)&#xD;
  &#xD;
                 -  Creatinine clearance (CrCl) &gt;= 30 mL/min/1.73m^2 as estimated per institution&#xD;
                    standards.&#xD;
  &#xD;
            -  Pre-study treatment tissue availability (sufficient tissue for 25 unstained slides) is&#xD;
               mandatory for enrollment. If tissue is determined to be insufficient/unsuitable, a&#xD;
               fresh biopsy prior to study therapy will be required.&#xD;
  &#xD;
            -  Human immunodeficiency virus (HIV) positive participants are eligible if on stable&#xD;
               dose of highly active antiretroviral therapy (HAART) for at least 3 months, CD4 counts&#xD;
               are &gt; 200 cells/mm^3 and viral load is undetectable.&#xD;
  &#xD;
            -  Hepatitis B virus (HBV) positive participants are eligible if they have been treated&#xD;
               or are on an appropriate course of antivirals at study entry and with planned&#xD;
               monitoring and management according to appropriate guidance. For previously treated&#xD;
               participants or those with prior infection that has been cleared, prophylaxis is&#xD;
               permitted, and hepatology consultation recommended.&#xD;
  &#xD;
            -  Hepatitis C virus (HCV) positive participants are eligible if participants are on&#xD;
               active HCV therapy at study entry and on a stable dose of antivirals without&#xD;
               documented clinically significant impaired liver function test or hematologic&#xD;
               abnormalities and with planned monitoring and management according to appropriate&#xD;
               labeling, or if they are post-treatment for HCV. Participants that are positive for&#xD;
               hepatitis C must have a negative polymerase chain reaction (PCR).&#xD;
  &#xD;
            -  Women of child-bearing potential (WOCBP) and men must agree to use an effective method&#xD;
               of contraception (barrier, surgical sterilization, abstinence for the duration of&#xD;
               study participation, and for at least 4 months after the last dose of study drug(s).&#xD;
  &#xD;
            -  Men must agree to use an effective method of contraception (barrier, surgical&#xD;
               sterilization, abstinence) for the duration of the study treatment and up to 4 months&#xD;
               after the last dose of the study drug(s). We also will recommend men with female&#xD;
               partners of childbearing potential to ask female partners to be on an effective birth&#xD;
               control (hormonal, intrauterine device (IUD), surgical sterilization).&#xD;
  &#xD;
            -  Breastfeeding participants must be willing to discontinue breastfeeding from study&#xD;
               treatment initiation through 4 months after the last dose of the pembrolizumab and 3&#xD;
               weeks after the last dose of EV.&#xD;
  &#xD;
            -  Participants must be able to understand and willing to sign a written informed consent&#xD;
               document.&#xD;
  &#xD;
          EXCLUSION CRITERIA:&#xD;
  &#xD;
            -  Participants with prior investigational drug, chemotherapy, immunotherapy, or any&#xD;
               prior radiotherapy (except for palliative bone directed therapy) within the past 2&#xD;
               weeks prior to the first study drug administration. Note: FDA-approved hormonal&#xD;
               therapy for the treatment or prevention of other malignancies (e.g., breast cancer,&#xD;
               prostate cancer) are allowed to be continued where in the opinion of the investigator&#xD;
               stopping such therapies may increase the risk of disease progression. Potential&#xD;
               drug-drug interactions with the hormonal agent will be assessed by the investigator&#xD;
               prior to enrollment.&#xD;
  &#xD;
            -  Participants with prior treatment with EV or other MMAE-based ADCs.&#xD;
  &#xD;
            -  Participants with preexisting sensory or motor neuropathy Grade &gt;= 2.&#xD;
  &#xD;
            -  History of severe allergic reactions attributed to compounds of similar chemical or&#xD;
               biologic composition to EV and/or pembrolizumab.&#xD;
  &#xD;
            -  Symptomatic or untreated central nervous system (CNS) metastases. Note: Participants&#xD;
               with previously treated brain or CNS metastases are eligible if the subjects have&#xD;
               recovered from any acute effects of radiotherapy and not requiring steroids, and any&#xD;
               whole brain radiation therapy or any stereotactic radiosurgery was completed at least&#xD;
               2 weeks prior to initiation of study therapy.&#xD;
  &#xD;
            -  Participants will be excluded if they have an active autoimmune disease that might&#xD;
               deteriorate when receiving pembrolizumab except for:&#xD;
  &#xD;
                 -  Diabetes type I, eczema, vitiligo, psoriasis, or hypo- or hyperthyroid diseases&#xD;
                    not requiring immunosuppressive treatment.&#xD;
  &#xD;
                 -  Subjects requiring hormone replacement with corticosteroids are eligible if the&#xD;
                    steroids are administered only for the purpose of hormonal replacement and at&#xD;
                    doses &lt;= 10 mg of prednisone or equivalent per day.&#xD;
  &#xD;
                 -  Administration of steroids for other conditions through a route known to result&#xD;
                    in a minimal systemic exposure (topical, intranasal, intro-ocular, or&#xD;
                    inhalation).&#xD;
  &#xD;
                 -  Subjects on systemic intravenous or oral corticosteroid therapy with the&#xD;
                    exception of physiologic doses of corticosteroids (&lt;= the equivalent of&#xD;
                    prednisone 10 mg/day) or other immunosuppressive agents such as azathioprine or&#xD;
                    cyclosporin A are excluded on the basis of potential immune suppression. For&#xD;
                    these subjects these excluded treatments must be discontinued at least 1 week&#xD;
                    prior to treatment initiation for recent short course use (&lt;= 14 days) or&#xD;
                    discontinued at least 4 weeks prior to treatment initiation for long term use (&gt;&#xD;
                    14 days). In addition, the use of corticosteroids as premedication for&#xD;
                    contrast-enhanced studies is allowed prior to treatment initiation and on study.&#xD;
  &#xD;
            -  History of uncontrolled diabetes mellitus within 3 months before the first dose of EV.&#xD;
               Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) &gt;= 8% or HbA1c between 7&#xD;
               and &lt; 8% with associated diabetes symptoms (polyuria or polydipsia) that are not&#xD;
               otherwise explained.&#xD;
  &#xD;
            -  Active keratitis or corneal ulcerations.&#xD;
  &#xD;
            -  Participants who have received or will receive a live vaccine within 30 days prior to&#xD;
               the first administration of study intervention. Seasonal flu vaccines that do not&#xD;
               contain a live virus are permitted. Locally approved COVID-19 vaccines are permitted.&#xD;
  &#xD;
            -  Pregnant women as evaluated by a positive serum or urine beta-human chorionic&#xD;
               gonadotropin (Beta-hCG) test at screening.&#xD;
  &#xD;
            -  Participants with severe uncontrolled intercurrent illness that would limit compliance&#xD;
               with study requirements, as evaluated by history, physical exam, and chemistry panel.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>120 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Andrea B Apolo, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>National Cancer Institute (NCI)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lisa Ley, R.N.</last_name>
      <phone>(240) 858-3524</phone>
      <email>lisa.ley@nih.gov</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Andrea B Apolo, M.D.</last_name>
      <phone>(301) 480-0536</phone>
      <email>apoloab@mail.nih.gov</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>National Institutes of Health Clinical Center</name>
        <address>
          <city>Bethesda</city>
          <state>Maryland</state>
          <zip>20892</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>National Cancer Institute Referral Office</last_name>
        <phone>888-624-1937</phone>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001533-C.html</url>
      <description>NIH Clinical Center Detailed Web Page</description>
    </link>
    <verification_date>September 12, 2023</verification_date>
    <study_first_submitted>September 15, 2023</study_first_submitted>
    <study_first_submitted_qc>September 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 15, 2023</last_update_submitted>
    <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Immunotherapy</keyword>
    <keyword>nectin 4</keyword>
    <keyword>rare genitourinary cancers</keyword>
    <keyword>programmed cell death 1 ligand 1</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms, Germ Cell and Embryonal</mesh_term>
      <mesh_term>Urinary Bladder Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pembrolizumab</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>.All collected IPD will be shared</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_time_frame>Data from this study may be requested from other researchers at least 1 year after the completion of the primary endpoint.</ipd_time_frame>
      <ipd_access_criteria>Data from this study may be requested by contacting the PI.</ipd_access_criteria>
    </patient_data>
    <!-- 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/NCT06041503
  org study id: 10001533
  secondary id: 001533-C
  nct id: NCT06041503
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  Background:
  
        Many cancers of the testicles and urinary tract are rare diseases; these are diseases that
        affect less than 200,000 people in the United States. It can be hard to study treatments for
        these diseases. One combination of drugs-enfortumab vedotin (EV) and pembrolizumab-has
        already been approved to treat some urinary cancers. Researchers want to see if they can help
        people with other types of testicle and urinary cancers.
  
        Objective:
  
        To test EV, with or without pembrolizumab, in patients with rarer cancers of the testicles or
        urinary tract.
  
        Eligibility:
  
        People aged 18 and older with rarer cancers of the testicles or urinary tract.
  
        Design:
  
        Participants will be screened. They will have a physical exam with blood and urine tests.
        Their ability to perform normal daily activities will be tested. They will have exams of
        their skin and eyes. They will have imaging scans. A biopsy may be needed: A sample of tissue
        will be removed from the tumor.
  
        The study drugs are both given through a tube attached to a needle inserted into a vein in
        the arm. Some participants will receive treatments 3 times during 28-week cycles; others will
        receive treatments 2 times during 21-day cycles.
  
        All participants may continue to receive treatments for up to 5 years. Imaging scans and
        other tests will be repeated.
  
        Participants who stop taking the drugs will have follow-up visits every 3 to 4 weeks until
        the disease gets worse. They will have imaging scans and blood tests.
  
        After that, follow-up visits will continue by phone every 3 months for up to 5 years after
        study therapy is finished.
  Background:
  
          -  Rare genitourinary (GU) tumors are tumors of aberrant histology occurring in the GU
             tract including kidney, bladder, ureters, testes, and penis. Due to their rarity, they
             are not systematically captured by currently available registries, treatment protocols
             or tissue banks.
  
          -  Large randomized clinical trials are logistically difficult in these small patient
             populations. Therefore, treatment information is obtained from case reports,
             retrospective studies, and small clinical trials, and is frequently extrapolated from
             trials on similar tumor types.
  
          -  Pembrolizumab is a potent and highly selective humanized monoclonal antibody that
             targets immune checkpoint programmed cell death protein 1 (PD-1) receptor.
  
          -  Nectin-4 is a type 1 transmembrane protein and member of a family of related
             immunoglobulinlike adhesion molecules implicated in cell-cell adhesion.
  
          -  Nectin-4 is highly expressed in cancer cells, particularly in urothelial carcinomas
             (UCs).
  
          -  Enfortumab vedotin (EV) is an antibody-drug conjugate consisting of a human monoclonal
             antibody to nectin-4 and monomethyl auristatin E (MMAE), a microtubule disrupting
             cytotoxic agent. EV has demonstrated a survival benefit in the setting of metastatic
             urothelial carcinoma, which has almost universally high nectin-4 expression.
  
          -  There is data in UC and bladder cancer variants showing co-existence of nectin-4
             expression and programmed cell death 1 ligand 1 (PD-L1) expression and mismatch repair
             deficiency.
  
          -  There is currently very limited data on the level of nectin-4 expression in rare GU
             tumors and no evidence for the activity of EV in these tumors.
  
        Objective:
  
        -To assess the objective response rate (ORR) per RECIST v 1.1 in participants with rare
        genitourinary (GU) tumors treated with enfortumab vedotin (EV) with or without pembrolizumab.
  
        Eligibility:
  
          -  Age >= 18 years
  
          -  Histologically confirmed diagnosis of locally advanced or metastatic pure adenocarcinoma
             of the bladder, pure squamous cell carcinoma of the bladder, or treatment-refractory
             testicular germ cell tumors.
  
          -  Participants may have received any number of prior anti-cancer treatments or be
             treatment na(SqrRoot) ve (with the exception of participants with testicular germ cell
             tumors, whom must have exhausted all standard curative-intent options).
  
        Design:
  
          -  This multisite study is a phase II, open label, multicohort, nonrandomized study with
             two arms.
  
          -  Participants with:
  
               -  Adenocarcinoma of the bladder will be enrolled in Cohort A (Cohort A1: prior
                  anti-1/PD-L1 therapy; Cohort A2: no prior anti-PD-1/PD-L1 therapy).
  
               -  Squamous cell carcinoma of the bladder will be enrolled in Cohort B (Cohort B1:
                  prior anti-PD-1/PD-L1 therapy; Cohort B2: no prior anti-PD-1/PD-L1 therapy).
  
               -  Testicular germ cell tumors will be enrolled in Cohort C (Cohort C1: prior
                  anti-PD-1/PDL1 therapy; Cohort C2: no prior anti-PD-1/PD-L1 therapy).
  
          -  All participants will receive EV.
  
          -  Participants without prior immune checkpoint inhibitor (ICI) exposure will be eligible
             to receive concurrent pembrolizumab.
  
          -  Arm 1: EV monotherapy will be given in 28-day cycles for a maximum of 5 years, or until
             disease progression or intolerable side effects. EV will be administered I.V. at 1.25
             mg/kg on days 1, 8, and 15 of each cycle.
  
          -  Arm 2: EV and pembrolizumab will be given in 21-day cycles. EV will be administered I.V.
             at 1.25 mg/kg on days 1 and 8 of each cycle. Pembrolizumab will be administered I.V. at
             200 mg on day 1.
  
               -  EV and pembrolizumab will be given for 35 cycles, or until a confirmed complete
                  response, disease progression or intolerable side effects.
  
               -  After the 35th cycle, EV may be continued to be given for a maximum of 5 years, or
                  until disease progression or intolerable side effects.
  
               -  Participants who have completed 35 cycles of pembrolizumab or stopped pembrolizumab
                  for confirmed complete response may be eligible for up to additional 17 cycles of
                  pembrolizumab if there is investigator-determined progressive disease by RECIST 1.1
                  after initial treatment.
  
          -  The accrual ceiling will be set at 68 participants to allow for inevaluable
             participants.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Objective response rate (ORR)
  time frame: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
  description: Percentage of participants by best overall response (e.g., CR, PR, SD, PD) to therapy
  measure: Second Objective response rate (ORR2) and second progression-free survival (PFS2) after second course of pembrolizumab
  time frame: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
  description: Percentage of participants with the best overall response of CR or PR to therapy and duration of time from start of treatment to time of progression or death, whichever occurs first.
  measure: Duration of response (DoR)
  time frame: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
  description: Time from start of treatment to disease progression or death in participants who achieve CR or PR
  measure: Overall survival (OS)
  time frame: Day 1 of each cycle, at EoT, at the Safety visits, and every 90 days for up to a total of 5 years after the end of therapy.
  description: Time from the start of treatment that participants are still alive.
  measure: Progression-free survival (PFS)
  time frame: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
  description: Duration of time from start of treatment to time of progression or death, whichever occurs first
  measure: Clinical benefit rate (CBR)
  time frame: At every restaging (prior to every 2nd or 3rd cycle) until the end of the study therapy and during follow-up until PD
  description: Percentage of participant who have achieved CR, PR, and SD while on treatment.
  measure: Safety of EV with or without pembrolizumab
  time frame: From first dose through 30 days after last treatment with EV and 90 days after last treatment with pembrolizumab
  description: Adverse events (AEs) will be reported by type and grade of toxicity
  arm group label: Arm 1
  arm group type: Experimental
  description: Treatment with enfortumab vedotin
  arm group label: Arm 2
  arm group type: Experimental
  description: Treatment with enfortumab vedotin and pembrolizumab
  intervention type: Drug
  intervention name: Enfortumab vedotin
  description: EV is administered IV at 1.25 mg/kg on days 1, 8, and 15 of each 28-day cycle or on days 1 and 8 of each 21-day cycle.
  arm group label: Arm 1
  arm group label: Arm 2
  intervention type: Drug
  intervention name: Pembrolizumab
  description: Pembrolizumab is administered IV at 200 mg on day 1 of each 21-day cycle.
  arm group label: Arm 2
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 120 Years
  healthy volunteers: No
  last name: Andrea B Apolo, M.D.
  role: Principal Investigator
  affiliation: National Cancer Institute (NCI)
  last name: Lisa Ley, R.N.
  phone: (240) 858-3524
  email: lisa.ley@nih.gov
  last name: Andrea B Apolo, M.D.
  phone: (301) 480-0536
  email: apoloab@mail.nih.gov
  facility: 
  contact: 
  country: United States
  url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001533-C.html
  description: NIH Clinical Center Detailed Web Page
  responsible party type: Sponsor
  mesh term: Neoplasms, Germ Cell and Embryonal
  mesh term: Urinary Bladder Neoplasms
  mesh term: Pembrolizumab
  sharing ipd: Yes
  ipd description: .All collected IPD will be shared
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd time frame: Data from this study may be requested from other researchers at least 1 year after the completion of the primary endpoint.
  ipd access criteria: Data from this study may be requested by contacting the PI.