<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/NCT03757689</url>
  </required_header>
  <id_info>
    <org_study_id>UPCC 09618</org_study_id>
    <secondary_id>832023</secondary_id>
    <secondary_id>CRU</secondary_id>
    <nct_id>NCT03757689</nct_id>
  </id_info>
  <brief_title>Neoadjuvant PD-1 Blockade in Patients With Stage IIB/C Melanoma</brief_title>
  <official_title>Neoadjuvant PD-1 Blockade in Patients With Stage IIB/C Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Abramson Cancer Center at Penn Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Abramson Cancer Center at Penn Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to determine the rate of positive sentinel lymph nodes&#xD;
      (i.e. the closest draining lymph node(s) to the primary melanoma site) and to test whether&#xD;
      treatment with pembrolizumab before surgery to remove melanoma reduces the rate of positive&#xD;
      sentinel lymph nodes in patients with Stage IIB/C melanoma.&#xD;
&#xD;
      Subjects with stage II melanoma will receive one dose of pembrolizumab 200 mg, then undergo&#xD;
      standard definitive surgery with wide excision and sentinel lymph node (SLN) biopsy&#xD;
      approximately 3 weeks after the initial dose of pembrolizumab. Post-operatively, subjects&#xD;
      will receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2019</start_date>
  <completion_date type="Anticipated">February 2026</completion_date>
  <primary_completion_date type="Anticipated">December 2024</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>SLN Positivity Rate</measure>
    <time_frame>3 Weeks</time_frame>
    <description>To determine the SLN positivity rate and test whether the SLN positivity rate is reduced in high risk stage II patients undergoing neoadjuvant PD-1 blockade.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and Tolerability as measured by observed adverse events.</measure>
    <time_frame>Approximately 5 Years</time_frame>
    <description>All observed adverse events which occur anytime from the initiation of study therapy to 30 days after the final dose of pembrolizumab will be graded and tabled.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease-Free Survival (DFS)</measure>
    <time_frame>Approximately 5 Years</time_frame>
    <description>Disease-free survival (DFS) is defined as the time from date of surgery to date of first documented disease progression, death due to any cause or last date that patient was documented to be disease-free (i.e., a scan date).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Approximately 5 Years</time_frame>
    <description>Overall survival (OS) is defined as the time from date of surgery to date of death due to any cause or last patient contact alive. Both DFS and OS outcomes will be measured from date of surgery to allow us to compare DFS and OS estimates with those of other adjuvant trials.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">63</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>Neoadjuvant Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive one dose of pembrolizumab 200 mg. Approximately 3 weeks after the initial dose of pembrolizumab, subjects will undergo wide excision and sentinel lymph node (SLN) biopsy. Post-operatively, subjects will receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pre-Surgery: Pembrolizumab, one 200mg dose; Post-Surgery: Pembrolizumab, 200 mg every 3 weeks.</description>
    <arm_group_label>Neoadjuvant Pembrolizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Wide Excision and Sentinel Lymph Node (SLN) Biopsy</intervention_name>
    <description>Wide excision and SLN biopsy and pathologic assessment of tissue will be performed per standard of care.</description>
    <arm_group_label>Neoadjuvant Pembrolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The subject must have clinical stage IIB or IIC resectable MEL. Subjects may not have&#xD;
             a diagnosis of uveal or mucosal melanoma.&#xD;
&#xD;
          -  Either the subject or the subject's legal representative must be willing and able to&#xD;
             provide written informed consent for the trial.&#xD;
&#xD;
          -  The subject must be ≥18 years of age on day of signing informed consent.&#xD;
&#xD;
          -  The subject must have a performance status of 0 or 1 on the ECOG Performance Scale.&#xD;
&#xD;
          -  The subject must demonstrate adequate organ function as defined in Table 1; all&#xD;
             screening labs must be performed within 21 days of treatment initiation.&#xD;
&#xD;
          -  System Laboratory Value&#xD;
&#xD;
               -  Hematologic&#xD;
&#xD;
                    -  ANC ≥1500/mcL&#xD;
&#xD;
                    -  Platelets ≥100,000/mcL&#xD;
&#xD;
                    -  Hemoglobin ≥9 g/dL or ≥5.6 mmol/L&#xD;
&#xD;
               -  Renal&#xD;
&#xD;
                    -  Serum creatinine OR measured or calculated creatinine clearance (GFR can&#xD;
                       also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal&#xD;
                       (ULN) OR&#xD;
&#xD;
                    -  ≥50 mL/min for subject with creatinine levels &gt;1.5 X institutional ULN&#xD;
&#xD;
               -  Hepatic&#xD;
&#xD;
                    -  Serum total bilirubin ≤1.5 X ULN OR&#xD;
&#xD;
                    -  Direct bilirubin ≤ ULN for subjects with total bilirubin levels &gt;1.5 ULN&#xD;
&#xD;
                    -  AST (SGOT) and ALT (SPGT) ≤2.5 X ULN OR ≤5 X ULN for subjects with liver&#xD;
                       metastases&#xD;
&#xD;
               -  Coagulation&#xD;
&#xD;
                    -  International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN&#xD;
                       unless subject is receiving anticoagulant therapy as long as PT or PTT is&#xD;
                       within therapeutic range of intended use of anticoagulants&#xD;
&#xD;
                    -  Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is&#xD;
                       receiving anticoagulant therapy as long as PT or PTT is within therapeutic&#xD;
                       range of intended use of anticoagulants&#xD;
&#xD;
          -  Female participants:&#xD;
&#xD;
               -  A female participant is eligible to participate if she is not pregnant (see&#xD;
                  Appendix 3), not breastfeeding, and at least one of the following conditions&#xD;
                  applies:&#xD;
&#xD;
               -  Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR&#xD;
&#xD;
               -  A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the&#xD;
                  treatment period and must be willing to use 2 methods of contraception or abstain&#xD;
                  from heterosexual intercourse for at least 2 weeks prior to the time of first&#xD;
                  dose of study medication through 120 days after the last dose of study&#xD;
                  medication.&#xD;
&#xD;
               -  Female subjects of childbearing potential must have a negative serum pregnancy&#xD;
                  test within 72 hours prior to receiving the first dose of study medication.&#xD;
&#xD;
               -  Female subjects of childbearing potential are defined as those women who have not&#xD;
                  been surgically sterilized or have not been free from menses for &gt;1 year.&#xD;
&#xD;
          -  Male participants:&#xD;
&#xD;
               -  Male subjects must agree to follow the contraceptive guidance in Appendix 3&#xD;
                  starting with the first dose of study medication, while on study, through 120&#xD;
                  days after the last dose of study medication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has unresectable disease; i.e. in the opinion of the surgical oncologist, all&#xD;
             of the subject's melanoma cannot be completely removed with a clear margin.&#xD;
&#xD;
          -  A woman of child bearing potential who has a positive urine pregnancy test within 72&#xD;
             hours prior to first dose of study drug (see Appendix 3). If the urine test is&#xD;
             positive or cannot be confirmed as negative, a serum pregnancy test will be required.&#xD;
&#xD;
        Note: In the event that 72 hours have elapsed between the screening pregnancy test and the&#xD;
        first dose of study treatment, another pregnancy test (urine or serum) must be performed&#xD;
        and must be negative in order for subject to start receiving study medication.&#xD;
&#xD;
          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with&#xD;
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,&#xD;
             CTLA-4, OX 40, CD137), interferon, high dose IL-2 or any other antibody or drug&#xD;
             specifically targeting T-cell co-stimulation or checkpoint pathways.&#xD;
&#xD;
          -  Has received prior systemic anti-cancer therapy including investigational agents&#xD;
             within 4 weeks Note: Participants must have recovered from all AEs due to previous&#xD;
             therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy are an&#xD;
             exception to this criterion.&#xD;
&#xD;
          -  If participant received major surgery, they must have recovered adequately from the&#xD;
             toxicity and/or complications from the intervention prior to starting study treatment.&#xD;
&#xD;
          -  Subject has received transfusion of blood products (including platelets or red blood&#xD;
             cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or&#xD;
             recombinant erythropoietin) within 4 weeks prior to study Day 1.&#xD;
&#xD;
          -  Has received a live vaccine within 30 days prior to the first dose of study drug.&#xD;
             Examples of live vaccines include, but are not limited to, the following: measles,&#xD;
             mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus&#xD;
             Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection&#xD;
             are generally killed virus vaccines and are allowed; however, intranasal influenza&#xD;
             vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.&#xD;
&#xD;
          -  Is currently participating in or has participated in a study of an investigational&#xD;
             agent or has used an investigational device within 4 weeks prior to the first dose of&#xD;
             study treatment.&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy&#xD;
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of&#xD;
             immunosuppressive therapy within 7 days prior to the first dose of study drug.&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment.&#xD;
             Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of&#xD;
             the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that&#xD;
             have undergone potentially curative therapy are not excluded.&#xD;
&#xD;
          -  Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.&#xD;
&#xD;
          -  Has active autoimmune disease that has required systemic treatment in the past 3&#xD;
             months (i.e. with use of disease modifying agents, corticosteroids or&#xD;
             immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or&#xD;
             physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,&#xD;
             etc.) is not considered a form of systemic treatment.&#xD;
&#xD;
          -  Has evidence of active interstitial lung disease or a history of (non-infectious)&#xD;
             pneumonitis that required steroids or has current pneumonitis.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy.&#xD;
&#xD;
          -  Has a known history of Human Immunodeficiency Virus (HIV). (HIV 1/2 antibodies) as&#xD;
             determined by medical record review.&#xD;
&#xD;
          -  Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]&#xD;
             reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection&#xD;
             as determined by medical record review.&#xD;
&#xD;
          -  Has a known history of active TB (Bacillus Tuberculosis).&#xD;
&#xD;
          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the study, interfere with the subject's&#xD;
             participation for the full duration of the study, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator.&#xD;
&#xD;
          -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the study, starting with the screening visit through 120 days&#xD;
             after the last dose of trial treatment.&#xD;
&#xD;
          -  Has severe cardiovascular disease, i.e. arrhythmias, requiring chronic treatment,&#xD;
             congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease.&#xD;
&#xD;
          -  Has hepatic decompensation (Child-Pugh score &gt;6 [class B and C]).&#xD;
&#xD;
          -  Has uncontrolled thyroid dysfunction.&#xD;
&#xD;
          -  Has uncontrolled diabetes mellitus.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Giorgos Karakousis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Abramson Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Giorgos Karakousis, MD</last_name>
    <phone>855-216-0098</phone>
    <email>penncancertrials@emergingmed.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Louisville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marilyn Donaldson, RN</last_name>
      <phone>502-629-3323</phone>
      <email>marilyn.donaldson@louisville.edu</email>
    </contact>
    <contact_backup>
      <last_name>Traci Hayat, RN</last_name>
      <phone>502-629-3383</phone>
      <email>traci.hayat@louisville.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Abramson Cancer Center of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Giorgos Karakousis, MD</last_name>
      <phone>855-216-0098</phone>
      <email>penncancertrials@emergingmed.com</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>July 10, 2023</last_update_submitted>
  <last_update_submitted_qc>July 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Stage IIB/C</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</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>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03757689
org study id: UPCC 09618
secondary id: 832023
secondary id: CRU
nct id: NCT03757689
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The main purpose of this study is to determine the rate of positive sentinel lymph nodes
      (i.e. the closest draining lymph node(s) to the primary melanoma site) and to test whether
      treatment with pembrolizumab before surgery to remove melanoma reduces the rate of positive
      sentinel lymph nodes in patients with Stage IIB/C melanoma.

      Subjects with stage II melanoma will receive one dose of pembrolizumab 200 mg, then undergo
      standard definitive surgery with wide excision and sentinel lymph node (SLN) biopsy
      approximately 3 weeks after the initial dose of pembrolizumab. Post-operatively, subjects
      will receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: SLN Positivity Rate
time frame: 3 Weeks
description: To determine the SLN positivity rate and test whether the SLN positivity rate is reduced in high risk stage II patients undergoing neoadjuvant PD-1 blockade.
measure: Safety and Tolerability as measured by observed adverse events.
time frame: Approximately 5 Years
description: All observed adverse events which occur anytime from the initiation of study therapy to 30 days after the final dose of pembrolizumab will be graded and tabled.
measure: Disease-Free Survival (DFS)
time frame: Approximately 5 Years
description: Disease-free survival (DFS) is defined as the time from date of surgery to date of first documented disease progression, death due to any cause or last date that patient was documented to be disease-free (i.e., a scan date).
measure: Overall Survival
time frame: Approximately 5 Years
description: Overall survival (OS) is defined as the time from date of surgery to date of death due to any cause or last patient contact alive. Both DFS and OS outcomes will be measured from date of surgery to allow us to compare DFS and OS estimates with those of other adjuvant trials.
arm group label: Neoadjuvant Pembrolizumab
arm group type: Experimental
description: Subjects will receive one dose of pembrolizumab 200 mg. Approximately 3 weeks after the initial dose of pembrolizumab, subjects will undergo wide excision and sentinel lymph node (SLN) biopsy. Post-operatively, subjects will receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks.
intervention type: Drug
intervention name: Pembrolizumab
description: Pre-Surgery: Pembrolizumab, one 200mg dose; Post-Surgery: Pembrolizumab, 200 mg every 3 weeks.
arm group label: Neoadjuvant Pembrolizumab
intervention type: Procedure
intervention name: Wide Excision and Sentinel Lymph Node (SLN) Biopsy
description: Wide excision and SLN biopsy and pathologic assessment of tissue will be performed per standard of care.
arm group label: Neoadjuvant Pembrolizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Giorgos Karakousis, MD
role: Principal Investigator
affiliation: Abramson Cancer Center
last name: Giorgos Karakousis, MD
phone: 855-216-0098
email: penncancertrials@emergingmed.com
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Pembrolizumab
sharing ipd: Undecided