<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/NCT03770455</url>
  </required_header>
  <id_info>
    <org_study_id>2018-1236</org_study_id>
    <nct_id>NCT03770455</nct_id>
  </id_info>
  <brief_title>Avelumab Plus 2nd-generation ADT in African American Subjects With mCRPC</brief_title>
  <official_title>PDL-1 Inhibition With Avelumab and Concurrent Second-generation ADT in African Americans With Castrate-resistant Metastatic Prostate Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jodi Layton, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>EMD Serono</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Tulane University</source>
  <oversight_info>
    <has_dmc>No</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>
      This is a nonrandomized, open-label trial of avelumab in subjects with metastatic&#xD;
      castration-resistant prostate cancer (mCRPC) experiencing PSA or radiographic progression&#xD;
      while receiving 2nd generation ADT (abiraterone / enzalutamide/ apalutamide or darolutamide).&#xD;
      Metastases must be radiographically evident by whole body bone scintigraphy or CT/MRI scan.&#xD;
&#xD;
      Thirteen African American subjects will be enrolled into the initial cohort.&#xD;
&#xD;
      If at least one positive response (PSA decrease by &gt;50% and or radiographic per RECIST 1.1)&#xD;
      is found, the study will be expanded to accrue a total of 27 patients. The trial will be&#xD;
      conducted in accordance with Good Clinical Practices.&#xD;
&#xD;
      Subjects enrolled in the study will receive avelumab 10 mg/kg every 2 weeks (Q2W) and&#xD;
      continue their previously started 2nd generation ADT (abiraterone or enzalutamide).&#xD;
&#xD;
      Treatment with avelumab will continue until documented confirmed disease progression,&#xD;
      unacceptable AEs, intercurrent illness that prevents further administration of treatment,&#xD;
      Investigator's decision to withdraw the subject, subject discontinuation from the study,&#xD;
      noncompliance with trial treatment or procedure requirements, subject receives 52&#xD;
      administrations of avelumab (approximately 2 years), or administrative reasons requiring the&#xD;
      cessation of treatment.&#xD;
&#xD;
      After the end of treatment, each subject will be followed for 30 days for AE monitoring&#xD;
      (serious AEs will be collected for 90 days after the end of treatment or 30 days after the&#xD;
      end of treatment if the subject initiates new anticancer therapy, whichever is earlier).&#xD;
      Subjects who discontinue treatment for reasons other than disease progression will remain on&#xD;
      study and continue to undergo study-related disease assessments until documented disease&#xD;
      progression, initiation of a new non-study prostate cancer treatment, withdrawal of consent,&#xD;
      or becoming lost to follow-up. All subjects will enter survival follow up, and will be&#xD;
      contacted at their regularly scheduled clinic visit, or by telephone approximately every 6&#xD;
      months, until death or withdrawal of consent or end of study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a nonrandomized, open-label trial of avelumab in subjects with metastatic&#xD;
      castration-resistant prostate cancer (mCRPC) experiencing PSA or radiographic progression&#xD;
      while receiving 2nd generation ADT (abiraterone / enzalutamide/ apalutamide or darolutamide).&#xD;
      Metastases must be radiographically evident by whole body bone scintigraphy or CT/MRI scan.&#xD;
&#xD;
      Thirteen African American subjects will be enrolled into the initial cohort. If at least one&#xD;
      positive response (PSA decrease by &gt;50% and or radiographic per RECIST 1.1) is found, the&#xD;
      study will be expanded to accrue a total of 27 patients. The trial will be conducted in&#xD;
      accordance with Good Clinical Practices.&#xD;
&#xD;
      Subjects enrolled in the study will receive avelumab 10 mg/kg every 2 weeks (Q2W) and&#xD;
      continue their previously started 2nd generation ADT (abiraterone or enzalutamide).&#xD;
&#xD;
      All subjects will undergo radiographic imaging assessments and PSA assessments to evaluate&#xD;
      response to treatment at regular intervals. On study imaging will be assessed every 12 weeks.&#xD;
      Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be adapted per the consensus&#xD;
      guidelines of the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) as described in&#xD;
      Appendix A/B to account for the tumor progression patterns seen in bone metastases in&#xD;
      prostate cancer. PSA will be obtained every 2 weeks with PSA progression assessed per PCWG3.&#xD;
&#xD;
      Adverse events (AEs) will be monitored throughout the trial and graded in severity according&#xD;
      to the guidelines outlined in the National Cancer Institute (NCI) Common Terminology Criteria&#xD;
      for Adverse Events (CTCAE) version 4.03.&#xD;
&#xD;
      Treatment with avelumab will continue until documented confirmed disease progression,&#xD;
      unacceptable AEs, intercurrent illness that prevents further administration of treatment,&#xD;
      Investigator's decision to withdraw the subject, subject discontinuation from the study,&#xD;
      noncompliance with trial treatment or procedure requirements, subject receives 52&#xD;
      administrations of avelumab (approximately 2 years), or administrative reasons requiring the&#xD;
      cessation of treatment.&#xD;
&#xD;
      After the end of treatment, each subject will be followed for 30 days for AE monitoring&#xD;
      (serious AEs will be collected for 90 days after the end of treatment or 30 days after the&#xD;
      end of treatment if the subject initiates new anticancer therapy, whichever is earlier).&#xD;
      Subjects who discontinue treatment for reasons other than disease progression will remain on&#xD;
      study and continue to undergo study-related disease assessments until documented disease&#xD;
      progression, initiation of a new non-study prostate cancer treatment, withdrawal of consent,&#xD;
      or becoming lost to follow-up. All subjects will enter survival follow up, and will be&#xD;
      contacted at their regularly scheduled clinic visit, or by telephone approximately every 6&#xD;
      months, until death or withdrawal of consent or end of study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Early signs of progression and learned experience that the assumed time period between psa&#xD;
    progression and radiographic progression was shorter than expected&#xD;
  </why_stopped>
  <start_date type="Actual">January 25, 2019</start_date>
  <completion_date type="Actual">January 7, 2021</completion_date>
  <primary_completion_date type="Actual">December 17, 2020</primary_completion_date>
  <phase>Phase 2</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>PSA Response Greater Than or Equal to 50%</measure>
    <time_frame>An interim analysis to assess responders will be performed at 2 years from date of enrolloment of first subject and at end of study.</time_frame>
    <description>The primary endpoint is a PSA response at 8 weeks or greater from starting study treatment and with a minimum of 3 treatments administered.&#xD;
A PSA response is defined as a ≥50% PSA decline at 8 weeks or greater from the time of starting study treatment. The two-stage minimax design of the study will be utilized to determine whether further investigation of the study drug is warranted.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PSA Progression-free Survival (PFS)</measure>
    <time_frame>pPFS will be assessed 12 months after enrollment of last subject.</time_frame>
    <description>PSA progression-free survival (pPFS) defined as the time from enrollment until PSA progression by PCWG3 or death, whichever occurs earlier. Subjects without pPFS at the time of data cut-off will be censored at the date of last adequate cancer assessment. PSA progression-free survival will be reported using Kaplan-Meier estimates, with 95% CI for median time-to-event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic Progression-free Survival (PFS)</measure>
    <time_frame>rPFS will be assessed 12 months after enrollment of last subject.</time_frame>
    <description>Radiographic progression-free survival (rPFS) defined as the time from enrollment until radiographic progression by PCWG3 or death, whichever occurs earlier. Subjects without rPFS at the time of data cut-off will be censored at the date of last known to be alive. Radiographic progression-free survival will be reported using Kaplan-Meier estimates, with 95% CI for median time-to-event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Overall survival with be assessed at 3 years from time of enrollment of last study subject.</time_frame>
    <description>Overall survival (OS) defined as the time from enrollment until death on study. Subjects who are alive at the time of data cut-off will be censored at the date of last known to be alive. OS will be reported using Kaplan-Meier estimates, with 95% CI for median time-to-event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events (AEs) Will be Summarized by Nature, Severity, and Frequency Utilizing CTCAE Version 4.03.</measure>
    <time_frame>Safety interim analysis will be performed at 2 years.</time_frame>
    <description>Safety will be summarized by nature, severity, and frequency utilizing CTCAE version 4.03.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Metastatic Castration-resistant Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Avelumab + 2nd generation ADT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Avelumab</intervention_name>
    <description>Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT</description>
    <arm_group_label>Avelumab + 2nd generation ADT</arm_group_label>
    <other_name>Bavencio</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>2nd generation ADT (abiraterone or enzalutamide)</intervention_name>
    <description>2nd generation ADT (abiraterone or enzalutamide)</description>
    <arm_group_label>Avelumab + 2nd generation ADT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Must be of African descent; Black or African American: A person having origins in any&#xD;
             of the black racial groups of Africa. Terms such as &quot;Haitian&quot; or &quot;Negro&quot; can be used&#xD;
             in addition to &quot;Black or African American.&quot;&#xD;
&#xD;
          2. Be willing and able to provide written informed consent for the trial.&#xD;
&#xD;
          3. Be ≥18 years of age on day of signing informed consent.&#xD;
&#xD;
          4. Have histologically or cytologically confirmed adenocarcinoma of the prostate without&#xD;
             small cell histology. Diagnosis must be stated in a pathology report.&#xD;
&#xD;
          5. Have evidence of metastatic disease as determined by CT/MRI scans and/or bone&#xD;
             metastases by whole body bone scintigraphy. (Use MRI if CT is contraindicated, and for&#xD;
             imaging of the brain if clinically indicated).&#xD;
&#xD;
          6. Have documented disease progression within 3 months of screening, as determined by the&#xD;
             Investigator, by means of at least one of the following:&#xD;
&#xD;
             PSA progression as defined by a minimum of two rising PSA levels with an interval of ≥&#xD;
             1 week between each assessment where the PSA value at screening should be ≥ 2 ng/mL.&#xD;
&#xD;
             Radiographic disease progression in soft tissue or bone with or without PSA&#xD;
             progression as determined by Recist 1.1 and/or PCWG3&#xD;
&#xD;
          7. Have ongoing androgen deprivation with serum testosterone &lt; 50 ng/dL (&lt; 2.0 nM). If&#xD;
             the subject is currently being treated with Luteinising Hormone Releasing Hormone&#xD;
             (LHRH) agonists or antagonists (for subjects who have not undergone an orchiectomy).&#xD;
             This treatment must be continued throughout the study.&#xD;
&#xD;
          8. Be receiving and tolerating either abiraterone acetate, enzalutamide, apalutamide or&#xD;
             darolutamide for at least 8 weeks prior to documented disease progression. Note: the&#xD;
             2nd generation ADT that the patient is currently progression on needs to be the first&#xD;
             2nd gen ADT used in the CRPC setting&#xD;
&#xD;
          9. Have a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group&#xD;
             (ECOG) Performance Scale (Appendix D).&#xD;
&#xD;
         10. Male subjects of reproductive potential must agree practice abstinence from&#xD;
             heterosexual activity OR use a highly effective method of contraception, starting at&#xD;
             the time of informed consent and continue through 60 days after the last dose of study&#xD;
             therapy (see section 6.1.1.)&#xD;
&#xD;
         11. Demonstrate adequate organ function as defined in Table 1, all screening labs should&#xD;
             be performed within 10 days of treatment initiation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Is currently participating and receiving study therapy in a clinical trial, or has&#xD;
             participated in a study of an investigational agent (and received study therapy or&#xD;
             used an investigation device) within 4 weeks of the first dose of study treatment.&#xD;
&#xD;
          2. No more than one line of a 2nd generation ADT (abiraterone acetate /enzalutamide/&#xD;
             apalutamide/darolutamide) for mCRPC is permitted for study entry.&#xD;
&#xD;
          3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any&#xD;
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial&#xD;
             treatment.&#xD;
&#xD;
             Note: the following are allowed: a. intranasal, inhaled, topical steroids, or local&#xD;
             steroid injection (e.g., intraarticular injection); b. systemic corticosteroids at&#xD;
             physiological doses &lt; 10mg/day of prednisone or equivalent; c. steroids as&#xD;
             premedication for hypersensitivity reactions (e.g., CT scan premedication).&#xD;
&#xD;
          4. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the&#xD;
             first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at&#xD;
             baseline) from adverse events due to mAbs administered more than 4 weeks earlier.&#xD;
&#xD;
          5. Has had &gt;2 prior systemic chemotherapy agents for mCRPC Note: chemotherapy in the&#xD;
             metastatic hormone sensitive prostate cancer (mHSPC) setting is allowed&#xD;
&#xD;
          6. Prior surgery within 4 weeks of initiating study treatment Note: If subjects received&#xD;
             major surgery, they must have recovered adequately from the toxicity and/or&#xD;
             complications from the intervention prior to the first dose of trial treatment.&#xD;
&#xD;
          7. Has any additional malignancy that has required active treatment in the last 3 years.&#xD;
&#xD;
             Exceptions include: basal cell carcinoma of the skin, squamous cell carcinoma of the&#xD;
             skin, or low-grade Ta or T1 urothelial carcinoma of that bladder that has undergone&#xD;
             potentially curative therapy.&#xD;
&#xD;
          8. Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis.&#xD;
&#xD;
             Note: Subjects with previously treated brain metastases may participate provided they&#xD;
             are stable (without evidence of progression by imaging for at least four weeks prior&#xD;
             to the first dose of trial treatment and any neurologic symptoms have returned to&#xD;
             baseline), have no evidence of new or enlarging brain metastases. This exception does&#xD;
             not include carcinomatous meningitis which is excluded regardless of clinical&#xD;
             stability.&#xD;
&#xD;
          9. Has an active autoimmune disease that might deteriorate when receiving an&#xD;
             immune-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo-&#xD;
             or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.&#xD;
&#xD;
         10. Has had prior organ transplantation including allogenic stem-cell transplantation.&#xD;
&#xD;
         11. Has an active infection requiring systemic therapy.&#xD;
&#xD;
         12. Has active, clinically significant Human Immunodeficiency Virus (HIV) (HIV 1/2&#xD;
             antibodies). Patients with well controlled HIV will be allowed to be enrolled into the&#xD;
             study.&#xD;
&#xD;
         13. Has Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening&#xD;
             (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is&#xD;
             positive).&#xD;
&#xD;
         14. Has received a live vaccine within 4 weeks of first dose of avelumab; live vaccines&#xD;
             are prohibited throughout course of the trial. Inactivated vaccines are allowed.&#xD;
&#xD;
         15. Has known prior severe hypersensitivity to investigational product or component in its&#xD;
             formulations, including known severe hypersensitivity reactions to monoclonal&#xD;
             antibodies (NCI CTCAE v4.3 Grade &gt; 3).&#xD;
&#xD;
         16. Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular&#xD;
             accident/stroke (&lt; 6months prior to enrollment), myocardial infarction (&lt; 6months&#xD;
             prior to enrollment), unstable angina, congestive heart failure (&gt; New York Heart&#xD;
             Association Classification Class II), or serious cardiac ventricular arrhythmia&#xD;
             requiring medication.&#xD;
&#xD;
         17. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.3 Grade &gt; 1); however,&#xD;
             alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety&#xD;
             risk based on investigator's judgment are acceptable.&#xD;
&#xD;
         18. Other severe acute or chronic medical conditions including colitis, inflammatory bowel&#xD;
             disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including&#xD;
             recent (within the past year) or active suicidal ideation or behavior; or laboratory&#xD;
             abnormalities that may increase the risk associated with study participation or study&#xD;
             treatment administration or may interfere with the interpretation of study results&#xD;
             and, in the judgment of the investigator, would make the patient inappropriate for&#xD;
             entry into this study.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Male based on biological distinctions not self-representation. Subject must have prostate cancer</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jodi L Layton, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tulane University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tulane University School of Medicine</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Graff JN, Alumkal JJ, Drake CG, Thomas GV, Redmond WL, Farhad M, Cetnar JP, Ey FS, Bergan RC, Slottke R, Beer TM. Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget. 2016 Aug 16;7(33):52810-52817. doi: 10.18632/oncotarget.10547.</citation>
    <PMID>27429197</PMID>
  </reference>
  <reference>
    <citation>Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. doi: 10.1056/NEJMoa1500596. Epub 2015 May 30.</citation>
    <PMID>26028255</PMID>
  </reference>
  <reference>
    <citation>Dominguez-Valentin M, Joost P, Therkildsen C, Jonsson M, Rambech E, Nilbert M. Frequent mismatch-repair defects link prostate cancer to Lynch syndrome. BMC Urol. 2016 Mar 24;16:15. doi: 10.1186/s12894-016-0130-1.</citation>
    <PMID>27013479</PMID>
  </reference>
  <reference>
    <citation>Raymond VM, Mukherjee B, Wang F, Huang SC, Stoffel EM, Kastrinos F, Syngal S, Cooney KA, Gruber SB. Elevated risk of prostate cancer among men with Lynch syndrome. J Clin Oncol. 2013 May 10;31(14):1713-8. doi: 10.1200/JCO.2012.44.1238. Epub 2013 Mar 25.</citation>
    <PMID>23530095</PMID>
  </reference>
  <reference>
    <citation>Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, Garofalo A, Gulati R, Carreira S, Eeles R, Elemento O, Rubin MA, Robinson D, Lonigro R, Hussain M, Chinnaiyan A, Vinson J, Filipenko J, Garraway L, Taplin ME, AlDubayan S, Han GC, Beightol M, Morrissey C, Nghiem B, Cheng HH, Montgomery B, Walsh T, Casadei S, Berger M, Zhang L, Zehir A, Vijai J, Scher HI, Sawyers C, Schultz N, Kantoff PW, Solit D, Robson M, Van Allen EM, Offit K, de Bono J, Nelson PS. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med. 2016 Aug 4;375(5):443-53. doi: 10.1056/NEJMoa1603144. Epub 2016 Jul 6.</citation>
    <PMID>27433846</PMID>
  </reference>
  <reference>
    <citation>Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010 Jul 29;363(5):411-22. doi: 10.1056/NEJMoa1001294.</citation>
    <PMID>20818862</PMID>
  </reference>
  <reference>
    <citation>Pritchard CC, Morrissey C, Kumar A, Zhang X, Smith C, Coleman I, Salipante SJ, Milbank J, Yu M, Grady WM, Tait JF, Corey E, Vessella RL, Walsh T, Shendure J, Nelson PS. Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer. Nat Commun. 2014 Sep 25;5:4988. doi: 10.1038/ncomms5988.</citation>
    <PMID>25255306</PMID>
  </reference>
  <reference>
    <citation>Escudier B, Motzer RJ, Sharma P, Wagstaff J, Plimack ER, Hammers HJ, Donskov F, Gurney H, Sosman JA, Zalewski PG, Harmenberg U, McDermott DF, Choueiri TK, Richardet M, Tomita Y, Ravaud A, Doan J, Zhao H, Hardy H, George S. Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025. Eur Urol. 2017 Sep;72(3):368-376. doi: 10.1016/j.eururo.2017.03.037. Epub 2017 Apr 12.</citation>
    <PMID>28410865</PMID>
  </reference>
  <reference>
    <citation>Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.</citation>
    <PMID>19097774</PMID>
  </reference>
  <reference>
    <citation>Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, Antonarakis ES, Beer TM, Carducci MA, Chi KN, Corn PG, de Bono JS, Dreicer R, George DJ, Heath EI, Hussain M, Kelly WK, Liu G, Logothetis C, Nanus D, Stein MN, Rathkopf DE, Slovin SF, Ryan CJ, Sartor O, Small EJ, Smith MR, Sternberg CN, Taplin ME, Wilding G, Nelson PS, Schwartz LH, Halabi S, Kantoff PW, Armstrong AJ; Prostate Cancer Clinical Trials Working Group 3. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016 Apr 20;34(12):1402-18. doi: 10.1200/JCO.2015.64.2702. Epub 2016 Feb 22.</citation>
    <PMID>26903579</PMID>
  </reference>
  <reference>
    <citation>Sartor et al. Overall Survival Analysis of African American and Caucasian Patients Receiving Sipuleucel-T: Preliminary Data from the Proceed Registry. J Urol, Vol 197: 4, April 2017.</citation>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>October 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <results_first_submitted>December 17, 2021</results_first_submitted>
  <results_first_submitted_qc>December 17, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 18, 2022</results_first_posted>
  <last_update_submitted>April 6, 2022</last_update_submitted>
  <last_update_submitted_qc>April 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Tulane University School of Medicine</investigator_affiliation>
    <investigator_full_name>Jodi Layton, MD</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Avelumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>all collected IPD, all IPD that underlie results in a publication</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>2022</ipd_time_frame>
    <ipd_access_criteria>TBD pending publication</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 25, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT03770455/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 16, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT03770455/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment Period: January 25, 2019 - 11 September 2020&#xD;
Location: Tulane Cancer Center</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Avelumab + 2nd Generation ADT</title>
          <description>Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT&#xD;
Avelumab: Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT&#xD;
2nd generation ADT (abiraterone or enzalutamide): 2nd generation ADT (abiraterone or enzalutamide)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Avelumab + 2nd Generation ADT</title>
          <description>Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT&#xD;
Avelumab: Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT&#xD;
2nd generation ADT (abiraterone or enzalutamide): 2nd generation ADT (abiraterone or enzalutamide)</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>PSA Response Greater Than or Equal to 50%</title>
        <description>The primary endpoint is a PSA response at 8 weeks or greater from starting study treatment and with a minimum of 3 treatments administered.&#xD;
A PSA response is defined as a ≥50% PSA decline at 8 weeks or greater from the time of starting study treatment. The two-stage minimax design of the study will be utilized to determine whether further investigation of the study drug is warranted.</description>
        <time_frame>An interim analysis to assess responders will be performed at 2 years from date of enrolloment of first subject and at end of study.</time_frame>
        <population>Study closed early due to safety concerns. Statistically underpowered and did not meet timeframe at 8 weeks for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + 2nd Generation ADT</title>
            <description>Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT&#xD;
Avelumab: Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT&#xD;
2nd generation ADT (abiraterone or enzalutamide): 2nd generation ADT (abiraterone or enzalutamide)</description>
          </group>
        </group_list>
        <measure>
          <title>PSA Response Greater Than or Equal to 50%</title>
          <description>The primary endpoint is a PSA response at 8 weeks or greater from starting study treatment and with a minimum of 3 treatments administered.&#xD;
A PSA response is defined as a ≥50% PSA decline at 8 weeks or greater from the time of starting study treatment. The two-stage minimax design of the study will be utilized to determine whether further investigation of the study drug is warranted.</description>
          <population>Study closed early due to safety concerns. Statistically underpowered and did not meet timeframe at 8 weeks for analysis.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PSA Progression-free Survival (PFS)</title>
        <description>PSA progression-free survival (pPFS) defined as the time from enrollment until PSA progression by PCWG3 or death, whichever occurs earlier. Subjects without pPFS at the time of data cut-off will be censored at the date of last adequate cancer assessment. PSA progression-free survival will be reported using Kaplan-Meier estimates, with 95% CI for median time-to-event.</description>
        <time_frame>pPFS will be assessed 12 months after enrollment of last subject.</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Radiographic Progression-free Survival (PFS)</title>
        <description>Radiographic progression-free survival (rPFS) defined as the time from enrollment until radiographic progression by PCWG3 or death, whichever occurs earlier. Subjects without rPFS at the time of data cut-off will be censored at the date of last known to be alive. Radiographic progression-free survival will be reported using Kaplan-Meier estimates, with 95% CI for median time-to-event.</description>
        <time_frame>rPFS will be assessed 12 months after enrollment of last subject.</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>Overall survival (OS) defined as the time from enrollment until death on study. Subjects who are alive at the time of data cut-off will be censored at the date of last known to be alive. OS will be reported using Kaplan-Meier estimates, with 95% CI for median time-to-event.</description>
        <time_frame>Overall survival with be assessed at 3 years from time of enrollment of last study subject.</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adverse Events (AEs) Will be Summarized by Nature, Severity, and Frequency Utilizing CTCAE Version 4.03.</title>
        <description>Safety will be summarized by nature, severity, and frequency utilizing CTCAE version 4.03.</description>
        <time_frame>Safety interim analysis will be performed at 2 years.</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year, 8 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Avelumab + 2nd Generation ADT</title>
          <description>Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT&#xD;
Avelumab: Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT&#xD;
2nd generation ADT (abiraterone or enzalutamide): 2nd generation ADT (abiraterone or enzalutamide)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>Standard terminology</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Colonic perforation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Lower back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>L2 compression fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Severe pain from back to leg/sciatica</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>Standard terminology</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Intermittent diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hypokaelmia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="10" subjects_affected="3" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Cramps</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin on feet</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Localized rash bilateral elbows</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Study did not reach target number of participants needed to reach target power for statistically reliable results due to poor recruitment during COIVD pandemic and early termination of study.&#xD;
Study closed early due to safety concerns regarding rapid clinical progression of several participants.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Jodi L. Layton, MD</name_or_title>
      <organization>Tulane University School of Medicine</organization>
      <phone>504-988-6121</phone>
      <email>jlayton@tulane.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03770455
org study id: 2018-1236
nct id: NCT03770455
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a nonrandomized, open-label trial of avelumab in subjects with metastatic
      castration-resistant prostate cancer (mCRPC) experiencing PSA or radiographic progression
      while receiving 2nd generation ADT (abiraterone / enzalutamide/ apalutamide or darolutamide).
      Metastases must be radiographically evident by whole body bone scintigraphy or CT/MRI scan.

      Thirteen African American subjects will be enrolled into the initial cohort.

      If at least one positive response (PSA decrease by >50% and or radiographic per RECIST 1.1)
      is found, the study will be expanded to accrue a total of 27 patients. The trial will be
      conducted in accordance with Good Clinical Practices.

      Subjects enrolled in the study will receive avelumab 10 mg/kg every 2 weeks (Q2W) and
      continue their previously started 2nd generation ADT (abiraterone or enzalutamide).

      Treatment with avelumab will continue until documented confirmed disease progression,
      unacceptable AEs, intercurrent illness that prevents further administration of treatment,
      Investigator's decision to withdraw the subject, subject discontinuation from the study,
      noncompliance with trial treatment or procedure requirements, subject receives 52
      administrations of avelumab (approximately 2 years), or administrative reasons requiring the
      cessation of treatment.

      After the end of treatment, each subject will be followed for 30 days for AE monitoring
      (serious AEs will be collected for 90 days after the end of treatment or 30 days after the
      end of treatment if the subject initiates new anticancer therapy, whichever is earlier).
      Subjects who discontinue treatment for reasons other than disease progression will remain on
      study and continue to undergo study-related disease assessments until documented disease
      progression, initiation of a new non-study prostate cancer treatment, withdrawal of consent,
      or becoming lost to follow-up. All subjects will enter survival follow up, and will be
      contacted at their regularly scheduled clinic visit, or by telephone approximately every 6
      months, until death or withdrawal of consent or end of study.
This is a nonrandomized, open-label trial of avelumab in subjects with metastatic
      castration-resistant prostate cancer (mCRPC) experiencing PSA or radiographic progression
      while receiving 2nd generation ADT (abiraterone / enzalutamide/ apalutamide or darolutamide).
      Metastases must be radiographically evident by whole body bone scintigraphy or CT/MRI scan.

      Thirteen African American subjects will be enrolled into the initial cohort. If at least one
      positive response (PSA decrease by >50% and or radiographic per RECIST 1.1) is found, the
      study will be expanded to accrue a total of 27 patients. The trial will be conducted in
      accordance with Good Clinical Practices.

      Subjects enrolled in the study will receive avelumab 10 mg/kg every 2 weeks (Q2W) and
      continue their previously started 2nd generation ADT (abiraterone or enzalutamide).

      All subjects will undergo radiographic imaging assessments and PSA assessments to evaluate
      response to treatment at regular intervals. On study imaging will be assessed every 12 weeks.
      Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be adapted per the consensus
      guidelines of the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) as described in
      Appendix A/B to account for the tumor progression patterns seen in bone metastases in
      prostate cancer. PSA will be obtained every 2 weeks with PSA progression assessed per PCWG3.

      Adverse events (AEs) will be monitored throughout the trial and graded in severity according
      to the guidelines outlined in the National Cancer Institute (NCI) Common Terminology Criteria
      for Adverse Events (CTCAE) version 4.03.

      Treatment with avelumab will continue until documented confirmed disease progression,
      unacceptable AEs, intercurrent illness that prevents further administration of treatment,
      Investigator's decision to withdraw the subject, subject discontinuation from the study,
      noncompliance with trial treatment or procedure requirements, subject receives 52
      administrations of avelumab (approximately 2 years), or administrative reasons requiring the
      cessation of treatment.

      After the end of treatment, each subject will be followed for 30 days for AE monitoring
      (serious AEs will be collected for 90 days after the end of treatment or 30 days after the
      end of treatment if the subject initiates new anticancer therapy, whichever is earlier).
      Subjects who discontinue treatment for reasons other than disease progression will remain on
      study and continue to undergo study-related disease assessments until documented disease
      progression, initiation of a new non-study prostate cancer treatment, withdrawal of consent,
      or becoming lost to follow-up. All subjects will enter survival follow up, and will be
      contacted at their regularly scheduled clinic visit, or by telephone approximately every 6
      months, until death or withdrawal of consent or end of study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PSA Response Greater Than or Equal to 50%
time frame: An interim analysis to assess responders will be performed at 2 years from date of enrolloment of first subject and at end of study.
description: The primary endpoint is a PSA response at 8 weeks or greater from starting study treatment and with a minimum of 3 treatments administered.
A PSA response is defined as a ≥50% PSA decline at 8 weeks or greater from the time of starting study treatment. The two-stage minimax design of the study will be utilized to determine whether further investigation of the study drug is warranted.
measure: PSA Progression-free Survival (PFS)
time frame: pPFS will be assessed 12 months after enrollment of last subject.
description: PSA progression-free survival (pPFS) defined as the time from enrollment until PSA progression by PCWG3 or death, whichever occurs earlier. Subjects without pPFS at the time of data cut-off will be censored at the date of last adequate cancer assessment. PSA progression-free survival will be reported using Kaplan-Meier estimates, with 95% CI for median time-to-event.
measure: Radiographic Progression-free Survival (PFS)
time frame: rPFS will be assessed 12 months after enrollment of last subject.
description: Radiographic progression-free survival (rPFS) defined as the time from enrollment until radiographic progression by PCWG3 or death, whichever occurs earlier. Subjects without rPFS at the time of data cut-off will be censored at the date of last known to be alive. Radiographic progression-free survival will be reported using Kaplan-Meier estimates, with 95% CI for median time-to-event.
measure: Overall Survival (OS)
time frame: Overall survival with be assessed at 3 years from time of enrollment of last study subject.
description: Overall survival (OS) defined as the time from enrollment until death on study. Subjects who are alive at the time of data cut-off will be censored at the date of last known to be alive. OS will be reported using Kaplan-Meier estimates, with 95% CI for median time-to-event.
measure: Adverse Events (AEs) Will be Summarized by Nature, Severity, and Frequency Utilizing CTCAE Version 4.03.
time frame: Safety interim analysis will be performed at 2 years.
description: Safety will be summarized by nature, severity, and frequency utilizing CTCAE version 4.03.
arm group label: Avelumab + 2nd generation ADT
arm group type: Experimental
description: Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT
intervention type: Drug
intervention name: Avelumab
description: Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT
arm group label: Avelumab + 2nd generation ADT
other name: Bavencio
intervention type: Drug
intervention name: 2nd generation ADT (abiraterone or enzalutamide)
description: 2nd generation ADT (abiraterone or enzalutamide)
arm group label: Avelumab + 2nd generation ADT
criteria: 
gender: Male
gender based: Yes
gender description: Male based on biological distinctions not self-representation. Subject must have prostate cancer
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jodi L Layton, MD
role: Principal Investigator
affiliation: Tulane University School of Medicine
facility: 
country: United States
citation: Graff JN, Alumkal JJ, Drake CG, Thomas GV, Redmond WL, Farhad M, Cetnar JP, Ey FS, Bergan RC, Slottke R, Beer TM. Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget. 2016 Aug 16;7(33):52810-52817. doi: 10.18632/oncotarget.10547.
PMID: 27429197
citation: Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. doi: 10.1056/NEJMoa1500596. Epub 2015 May 30.
PMID: 26028255
citation: Dominguez-Valentin M, Joost P, Therkildsen C, Jonsson M, Rambech E, Nilbert M. Frequent mismatch-repair defects link prostate cancer to Lynch syndrome. BMC Urol. 2016 Mar 24;16:15. doi: 10.1186/s12894-016-0130-1.
PMID: 27013479
citation: Raymond VM, Mukherjee B, Wang F, Huang SC, Stoffel EM, Kastrinos F, Syngal S, Cooney KA, Gruber SB. Elevated risk of prostate cancer among men with Lynch syndrome. J Clin Oncol. 2013 May 10;31(14):1713-8. doi: 10.1200/JCO.2012.44.1238. Epub 2013 Mar 25.
PMID: 23530095
citation: Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, Garofalo A, Gulati R, Carreira S, Eeles R, Elemento O, Rubin MA, Robinson D, Lonigro R, Hussain M, Chinnaiyan A, Vinson J, Filipenko J, Garraway L, Taplin ME, AlDubayan S, Han GC, Beightol M, Morrissey C, Nghiem B, Cheng HH, Montgomery B, Walsh T, Casadei S, Berger M, Zhang L, Zehir A, Vijai J, Scher HI, Sawyers C, Schultz N, Kantoff PW, Solit D, Robson M, Van Allen EM, Offit K, de Bono J, Nelson PS. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med. 2016 Aug 4;375(5):443-53. doi: 10.1056/NEJMoa1603144. Epub 2016 Jul 6.
PMID: 27433846
citation: Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010 Jul 29;363(5):411-22. doi: 10.1056/NEJMoa1001294.
PMID: 20818862
citation: Pritchard CC, Morrissey C, Kumar A, Zhang X, Smith C, Coleman I, Salipante SJ, Milbank J, Yu M, Grady WM, Tait JF, Corey E, Vessella RL, Walsh T, Shendure J, Nelson PS. Complex MSH2 and MSH6 mutations in hypermutated microsatellite unstable advanced prostate cancer. Nat Commun. 2014 Sep 25;5:4988. doi: 10.1038/ncomms5988.
PMID: 25255306
citation: Escudier B, Motzer RJ, Sharma P, Wagstaff J, Plimack ER, Hammers HJ, Donskov F, Gurney H, Sosman JA, Zalewski PG, Harmenberg U, McDermott DF, Choueiri TK, Richardet M, Tomita Y, Ravaud A, Doan J, Zhao H, Hardy H, George S. Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025. Eur Urol. 2017 Sep;72(3):368-376. doi: 10.1016/j.eururo.2017.03.037. Epub 2017 Apr 12.
PMID: 28410865
citation: Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PMID: 19097774
citation: Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, Antonarakis ES, Beer TM, Carducci MA, Chi KN, Corn PG, de Bono JS, Dreicer R, George DJ, Heath EI, Hussain M, Kelly WK, Liu G, Logothetis C, Nanus D, Stein MN, Rathkopf DE, Slovin SF, Ryan CJ, Sartor O, Small EJ, Smith MR, Sternberg CN, Taplin ME, Wilding G, Nelson PS, Schwartz LH, Halabi S, Kantoff PW, Armstrong AJ; Prostate Cancer Clinical Trials Working Group 3. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016 Apr 20;34(12):1402-18. doi: 10.1200/JCO.2015.64.2702. Epub 2016 Feb 22.
PMID: 26903579
citation: Sartor et al. Overall Survival Analysis of African American and Caucasian Patients Receiving Sipuleucel-T: Preliminary Data from the Proceed Registry. J Urol, Vol 197: 4, April 2017.
responsible party type: Sponsor-Investigator
investigator affiliation: Tulane University School of Medicine
investigator full name: Jodi Layton, MD
investigator title: Assistant Professor of Medicine
mesh term: Prostatic Neoplasms
mesh term: Avelumab
sharing ipd: Yes
ipd description: all collected IPD, all IPD that underlie results in a publication
ipd info type: Study Protocol
ipd info type: Clinical Study Report (CSR)
ipd time frame: 2022
ipd access criteria: TBD pending publication
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study did not reach target number of participants needed to reach target power for statistically reliable results due to poor recruitment during COIVD pandemic and early termination of study.
Study closed early due to safety concerns regarding rapid clinical progression of several participants.
point of contact: 