<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/NCT03241186</url>
  </required_header>
  <id_info>
    <org_study_id>MEL16-252</org_study_id>
    <nct_id>NCT03241186</nct_id>
  </id_info>
  <brief_title>Ipilimumab and Nivolumab as Adjuvant Treatment of Mucosal Melanoma</brief_title>
  <official_title>Single Arm Phase II Study of Ipilimumab and Nivolumab as Adjuvant Therapy for Resected Mucosal Melanoma (SALVO Study). HCRN: MEL16-252</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Robert R. McWilliams, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hoosier Cancer Research Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hoosier Cancer Research Network</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>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a single arm phase II clinical trial of Ipilimumab and Nivolumab in patients with&#xD;
      resected mucosal melanoma. Ipilimumab (1 mg/kg) and Nivolumab (3 mg/kg) will be administered&#xD;
      Day 1 of a 21-day cycle in Cycles 1-4 and then nivolumab 480 mg will be administered Day 1 of&#xD;
      a 28-day cycle for Cycles 5-15 (maximum of 15) or until disease recurrence or intolerance&#xD;
      before completion of 15 cycles.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ipilimumab and Nivolumab Combination Administration&#xD;
&#xD;
        -  Ipilimumab 1mg/kg given IV Day 1 for 3 weeks (21 days), for 4 cycles&#xD;
&#xD;
        -  Nivolumab 3mg/kg given IV Day 1 for 3 weeks (21 days), for 4 cycles&#xD;
&#xD;
      Nivolumab Alone Administration&#xD;
&#xD;
        -  Nivolumab 480mg given IV Day 1 for 4 weeks (28 days), for 5-15 cycles&#xD;
&#xD;
      Nivolumab is to be administered as an approximately 30-minute IV infusion (± 10 minutes). At&#xD;
      the end of the infusion, flush the line with a sufficient quantity of normal saline.&#xD;
&#xD;
      Ipilimumab is to be administered as an approximately 30-minute IV infusion (± 10 minutes). At&#xD;
      the end of the infusion, flush the line with a sufficient quantity of normal saline or 5%&#xD;
      dextrose solution.&#xD;
&#xD;
      When both study drugs are to be administered on the same day, separate infusion bags and&#xD;
      filters must be used for each infusion. Nivolumab is to be administered first. The nivolumab&#xD;
      infusion must be promptly followed by a saline flush to clear the line of nivolumab before&#xD;
      starting the ipilimumab infusion. The second infusion will always be ipilimumab, and will&#xD;
      start at least 30 minutes after completion of the nivolumab infusion.&#xD;
&#xD;
      The dosing calculations should be based on the body weight from Cycle 1 Day 1. If the&#xD;
      subject's weight on the day of dosing differs by &gt; 5% from the weight used to calculate the&#xD;
      dose, the dose should be recalculated based on the current day of treatment weight. All doses&#xD;
      should be rounded to the nearest milligram. There will be no dose modifications allowed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 12, 2017</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Actual">September 15, 2022</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>
    <masking_description>Open Label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Assess Recurrence-free survival time (RFS)</measure>
    <time_frame>1.5 years</time_frame>
    <description>Date the patient receives the first dose of study medication to the date of documentation of first disease recurrence or death due to any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess the Adverse Events</measure>
    <time_frame>2 years</time_frame>
    <description>Adverse events will be graded and attribution assigned using CTCAE version 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>2 years</time_frame>
    <description>The time from registration to death due to any cause</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Mucosal Melanoma</condition>
  <arm_group>
    <arm_group_label>Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cycles 1-4: Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV Day 1 of each Cycle Each Cycle = 21 days&#xD;
Cycles 5-15: Nivolumab IV 480 mg Day 1 of each Cycle Each Cycle = 28 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>1mg/kg</description>
    <arm_group_label>Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV</arm_group_label>
    <other_name>Yervoy</other_name>
    <other_name>BMS-734016</other_name>
    <other_name>MDX010</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>3mg/kg</description>
    <arm_group_label>Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV</arm_group_label>
    <other_name>OPDIVO</other_name>
    <other_name>BMS-936558</other_name>
    <other_name>ONO-4538</other_name>
    <other_name>MDX1106</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>480mg</description>
    <arm_group_label>Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV</arm_group_label>
    <other_name>OPDIVO</other_name>
    <other_name>BMS-936558</other_name>
    <other_name>ONO-4538</other_name>
    <other_name>MDX1106</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subject must meet all of the following applicable inclusion criteria to participate in this&#xD;
        study:&#xD;
&#xD;
          -  Histological confirmation of melanoma of any mucosal site including (but not limited&#xD;
             to) anus/rectum, vulvar/vaginal, sinonasal. NOTE: Melanomas of cutaneous origin and/or&#xD;
             ocular origin are ineligible.&#xD;
&#xD;
          -  R0 or R1 resection of primary melanoma tumor (no gross disease can be left behind, but&#xD;
             microscopically positive margins are acceptable).&#xD;
&#xD;
          -  Surgery within ≤ 90 days of registration.&#xD;
&#xD;
          -  ECOG Performance Status (PS) ≤ 1&#xD;
&#xD;
        The following laboratory values obtained ≤ 14 days prior to registration:&#xD;
&#xD;
        Hematological:&#xD;
&#xD;
          -  Absolute Neutrophil Count (ANC) ≥ 1500/mm^3&#xD;
&#xD;
          -  Hemoglobin (Hgb) ≥ 9 g/dL (may be transfused)&#xD;
&#xD;
          -  Platelet (Plt) 100,000/mm^3&#xD;
&#xD;
        Renal:&#xD;
&#xD;
          -  Serum Creatinine ≤ 1.5 x ULN&#xD;
&#xD;
        Hepatic:&#xD;
&#xD;
          -  Alkaline Phosphatase (Alk Phos) ≤ 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
          -  Total and Direct Bilirubin ≤ 1.5 × (ULN)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) ≤ 1.5 × ULN&#xD;
&#xD;
          -  Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing&#xD;
             potential only. NOTE: Females are considered of child bearing potential unless they&#xD;
             are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or&#xD;
             bilateral oophorectomy) or they are naturally postmenopausal for at least 12&#xD;
             consecutive months.&#xD;
&#xD;
          -  Written informed consent and HIPAA authorization for release of personal health&#xD;
             information prior to registration. NOTE: HIPAA authorization may be included in the&#xD;
             informed consent or obtained separately.&#xD;
&#xD;
          -  Willing to return to enrolling institution for follow-up&#xD;
&#xD;
          -  Willing to provide archival tissue prior to C1D1 if available and blood samples for&#xD;
             correlative research purposes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects meeting any of the criteria below may not participate in the study:&#xD;
&#xD;
          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment&#xD;
             of the investigator, would make the subject inappropriate for entry into this study or&#xD;
             interfere significantly with the proper assessment of safety and toxicity of the&#xD;
             prescribed regimens.&#xD;
&#xD;
          -  Immunocompromised patients and subjects known to be HIV positive and currently&#xD;
             receiving antiretroviral therapy. NOTE: Subjects known to be HIV positive, but without&#xD;
             clinical evidence of an immunocompromised state, are eligible for this trial.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#xD;
&#xD;
          -  Receiving any other investigational agent which would be considered as a treatment for&#xD;
             the primary neoplasm.&#xD;
&#xD;
          -  Other active malignancy ≤ 3 years prior to registration. EXCEPTIONS: Malignancies with&#xD;
             a very low (&lt; 5%) risk of recurrence such as non-melanotic skin cancer or&#xD;
             carcinoma-in-situ of the cervix.&#xD;
&#xD;
          -  History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use&#xD;
             of ongoing maintenance therapy for life-threatening ventricular arrhythmias.&#xD;
&#xD;
          -  Active autoimmune disease -including but not limited to:&#xD;
&#xD;
               -  Subjects with a history of inflammatory bowel disease, including ulcerative&#xD;
                  colitis and Crohn's Disease,&#xD;
&#xD;
               -  Subjects with a history of symptomatic autoimmune disease requiring systemic&#xD;
                  treatment within the past 2 years with the use of disease modifying agents,&#xD;
                  corticosteroids, or immunosuppressive drugs.&#xD;
&#xD;
                    -  rheumatoid arthritis&#xD;
&#xD;
                    -  systemic progressive sclerosis (scleroderma)&#xD;
&#xD;
                    -  systemic lupus erythematosus&#xD;
&#xD;
                    -  psoriasis&#xD;
&#xD;
                    -  autoimmune vasculitis (e.g., Wegener's Granulomatosis)&#xD;
&#xD;
                    -  CNS or motor neuropathy considered of autoimmune origin (e.g.,&#xD;
                       Guillain-Barre Syndrome and Myasthenia Gravis, multiple sclerosis)&#xD;
&#xD;
        EXCEPTION: autoimmune conditions that are only requiring replacement therapy (e.g.,&#xD;
        thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or&#xD;
        pituitary insufficiency, etc.) is not considered a form of systemic treatment.&#xD;
&#xD;
          -  Any radiation within 2 weeks prior to study initiation. Neoadjuvant and adjuvant&#xD;
             radiation are allowed, but must be completed &gt; 2 weeks prior to registration.&#xD;
&#xD;
          -  Any prior systemic therapy for melanoma (chemotherapy, immunotherapy, targeted&#xD;
             therapy)&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP) must be willing to abstain from heterosexual&#xD;
             intercourse or to use 2 forms of effective methods of contraception from the time of&#xD;
             informed consent until 5 months after the last dose of study drug. The two&#xD;
             contraception methods can be comprised of two barrier methods, or a barrier method&#xD;
             plus a hormonal method. Examples include: intrauterine device (IUD), vasectomy of a&#xD;
             female subject's male partner, contraceptive rod implanted into the skin, or use of&#xD;
             two of the following: diaphragm with spermicide (cannot be used in conjunction with&#xD;
             cervical cap/spermicide), cervical cap with spermicide (nulliparous women only),&#xD;
             contraceptive sponge (nulliparous women only), male condom or female condom (cannot be&#xD;
             used together), hormonal contraceptive.*Abstinence is acceptable if this is the usual&#xD;
             lifestyle and preferred contraception for the subject. NOTE: Male subjects are not&#xD;
             required to utilize contraception. The study regimen is not genotoxic and systemic&#xD;
             concentrations sufficient to produce a risk of fetal toxicity are not expected in&#xD;
             WOCBP partners from exposure to a male participant's seminal fluid.&#xD;
&#xD;
          -  Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the&#xD;
             mother is being treated on study).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert R. McWilliams, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Hoosier Cancer Research Network</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic- Florida</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospital and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>555455455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nebraska Cancer Specialists</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.hoosiercancer.org</url>
    <description>Hoosier Cancer Research Network Website</description>
  </link>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>December 8, 2022</last_update_submitted>
  <last_update_submitted_qc>December 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Hoosier Cancer Research Network</investigator_affiliation>
    <investigator_full_name>Robert R. McWilliams, MD</investigator_full_name>
    <investigator_title>Sponsor-Investigator</investigator_title>
  </responsible_party>
  <keyword>Ipilimumab</keyword>
  <keyword>Nivolumab</keyword>
  <keyword>OPDIVO</keyword>
  <keyword>IgG4 kappa immunoglobulin</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>Nivolumab</mesh_term>
    <mesh_term>Ipilimumab</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/NCT03241186
org study id: MEL16-252
nct id: NCT03241186
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a single arm phase II clinical trial of Ipilimumab and Nivolumab in patients with
      resected mucosal melanoma. Ipilimumab (1 mg/kg) and Nivolumab (3 mg/kg) will be administered
      Day 1 of a 21-day cycle in Cycles 1-4 and then nivolumab 480 mg will be administered Day 1 of
      a 28-day cycle for Cycles 5-15 (maximum of 15) or until disease recurrence or intolerance
      before completion of 15 cycles.
Ipilimumab and Nivolumab Combination Administration

        -  Ipilimumab 1mg/kg given IV Day 1 for 3 weeks (21 days), for 4 cycles

        -  Nivolumab 3mg/kg given IV Day 1 for 3 weeks (21 days), for 4 cycles

      Nivolumab Alone Administration

        -  Nivolumab 480mg given IV Day 1 for 4 weeks (28 days), for 5-15 cycles

      Nivolumab is to be administered as an approximately 30-minute IV infusion (± 10 minutes). At
      the end of the infusion, flush the line with a sufficient quantity of normal saline.

      Ipilimumab is to be administered as an approximately 30-minute IV infusion (± 10 minutes). At
      the end of the infusion, flush the line with a sufficient quantity of normal saline or 5%
      dextrose solution.

      When both study drugs are to be administered on the same day, separate infusion bags and
      filters must be used for each infusion. Nivolumab is to be administered first. The nivolumab
      infusion must be promptly followed by a saline flush to clear the line of nivolumab before
      starting the ipilimumab infusion. The second infusion will always be ipilimumab, and will
      start at least 30 minutes after completion of the nivolumab infusion.

      The dosing calculations should be based on the body weight from Cycle 1 Day 1. If the
      subject's weight on the day of dosing differs by > 5% from the weight used to calculate the
      dose, the dose should be recalculated based on the current day of treatment weight. All doses
      should be rounded to the nearest milligram. There will be no dose modifications allowed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open Label
measure: Assess Recurrence-free survival time (RFS)
time frame: 1.5 years
description: Date the patient receives the first dose of study medication to the date of documentation of first disease recurrence or death due to any cause.
measure: Assess the Adverse Events
time frame: 2 years
description: Adverse events will be graded and attribution assigned using CTCAE version 4
measure: Overall Survival (OS)
time frame: 2 years
description: The time from registration to death due to any cause
arm group label: Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV
arm group type: Experimental
description: Cycles 1-4: Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV Day 1 of each Cycle Each Cycle = 21 days
Cycles 5-15: Nivolumab IV 480 mg Day 1 of each Cycle Each Cycle = 28 days
intervention type: Drug
intervention name: Ipilimumab
description: 1mg/kg
arm group label: Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV
other name: Yervoy
other name: BMS-734016
other name: MDX010
intervention type: Drug
intervention name: Nivolumab
description: 3mg/kg
arm group label: Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV
other name: OPDIVO
other name: BMS-936558
other name: ONO-4538
other name: MDX1106
intervention type: Drug
intervention name: Nivolumab
description: 480mg
arm group label: Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV
other name: OPDIVO
other name: BMS-936558
other name: ONO-4538
other name: MDX1106
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Robert R. McWilliams, MD
role: Study Chair
affiliation: Hoosier Cancer Research Network
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.hoosiercancer.org
description: Hoosier Cancer Research Network Website
responsible party type: Sponsor-Investigator
investigator affiliation: Hoosier Cancer Research Network
investigator full name: Robert R. McWilliams, MD
investigator title: Sponsor-Investigator
mesh term: Melanoma
mesh term: Nivolumab
mesh term: Ipilimumab
sharing ipd: Undecided