<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/NCT04416568</url>
  </required_header>
  <id_info>
    <org_study_id>20-041</org_study_id>
    <nct_id>NCT04416568</nct_id>
  </id_info>
  <brief_title>Study of Nivolumab and Ipilimumab in Children and Young Adults With INI1-Negative Cancers</brief_title>
  <official_title>Phase 2 Proof of Concept Study of Nivolumab and Ipilimumab in Children and Young Adults With Relapsed or Refractory INI1-negative Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Gateway for Cancer Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This clinical trial is studying two immunotherapy drugs (nivolumab and ipilimumab) given&#xD;
      together as a possible treatment for INI1-negative tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is a Phase II clinical trial, which tests the safety and effectiveness of&#xD;
      an investigational drug or drug combination to learn whether the drug or drug combination&#xD;
      works in treating a specific disease. &quot;Investigational&quot; means that the drug combination is&#xD;
      being studied.&#xD;
&#xD;
      The names of the study drugs involved in this study are:&#xD;
&#xD;
        -  Nivolumab (OPDIVO)&#xD;
&#xD;
        -  Ipilimumab (YERYOY)&#xD;
&#xD;
      This trial is studying whether nivolumab and ipilimumab work to treat INI1-negative cancers.&#xD;
&#xD;
      The U.S. Food and Drug Administration (FDA) has not approved combination nivolumab and&#xD;
      ipilimumab for the specific diseases in this study but it has been approved for other&#xD;
      diseases. Nivolumab and ipilimumab have been tested in children to find out a safe dose of&#xD;
      this combination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 14, 2020</start_date>
  <completion_date type="Anticipated">October 2025</completion_date>
  <primary_completion_date type="Anticipated">October 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Overall Response Rate (Stratum 1)</measure>
    <time_frame>12 months</time_frame>
    <description>Based on Response Evaluation in Solid Tumors (RECIST) version 1.1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective Overall Response Rate (Stratum 2)</measure>
    <time_frame>12 months</time_frame>
    <description>Based on Response Assessment in Neuro-Oncology (RANO) Criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>3 years</time_frame>
    <description>Time from study enrollment until the first occurrence of disease progression, relapse or death due to disease</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>3 years</time_frame>
    <description>Time from study enrollment until death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate at 12 months</measure>
    <time_frame>12 Months</time_frame>
    <description>The proportion of patients who are progression-free at 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of toxicities (Grade 3-5 per CTCAE)</measure>
    <time_frame>13 months</time_frame>
    <description>Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Malignant Rhabdoid Tumor</condition>
  <condition>Rhabdoid Tumor of the Kidney</condition>
  <condition>Epithelioid Sarcoma</condition>
  <condition>Chordoma (Poorly Differentiated or De-differentiated)</condition>
  <condition>Atypical Teratoid/Rhabdoid Tumor</condition>
  <condition>Other INI1 Negative Tumors (With PI Approval)</condition>
  <condition>Other SMARCA4-deficient Malignant Tumors (With PI Approval)</condition>
  <arm_group>
    <arm_group_label>Solid Tumor (Stratum 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive combination therapy with nivolumab at a predetermined dose and ipilimumab at a predetermined dose day 1 of a 21-day cycle for 4 cycles&#xD;
Starting with cycle 5, patients will receive nivolumab monotherapy at a predetermined dose on day 1 and day 15 of a 28-day cycle&#xD;
Patients with INI1-negative relapsed or refractory extracranial solid tumors</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CNS (Stratum 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive combination therapy with nivolumab at a predetermined dose and ipilimumab at a predetermined dose day 1 of a 21-day cycle for 4 cycles&#xD;
Starting with cycle 5, patients will receive nivolumab monotherapy at a predetermined dose on day 1 and day 15 of a 28-day cycle&#xD;
Patients with INI1-negative relapsed or refractory CNS tumors</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Combination Therapy: Nivolumab at predetermined dosage day 1 of a 21-day cycle for 4 cycles.&#xD;
Monotherapy: Starting with cycle 5 nivolumab at predetermined dosage on day 1 and day 15 of a 28-day cycle</description>
    <arm_group_label>CNS (Stratum 2)</arm_group_label>
    <arm_group_label>Solid Tumor (Stratum 1)</arm_group_label>
    <other_name>OPDIVO</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>Combination Therapy: Ipilimumab at predetermined dosage day 1 of a 21-day cycle for 4 cycles</description>
    <arm_group_label>CNS (Stratum 2)</arm_group_label>
    <arm_group_label>Solid Tumor (Stratum 1)</arm_group_label>
    <other_name>YERYOY</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All participants must have one of the following histologically confirmed tumors at&#xD;
             original diagnosis or relapse:&#xD;
&#xD;
               -  Stratum 1&#xD;
&#xD;
                    -  Malignant rhabdoid tumor (MRT)&#xD;
&#xD;
                    -  Rhabdoid tumor of the kidney (RTK)&#xD;
&#xD;
                    -  Epithelioid sarcoma&#xD;
&#xD;
                    -  Chordoma (poorly differentiated or de-differentiated)&#xD;
&#xD;
                    -  Other INI1-negative or SMARCA4-deficient malignant tumors (with PI approval)&#xD;
&#xD;
               -  Stratum 2&#xD;
&#xD;
                    -  Atypical teratoid rhabdoid tumor (ATRT)&#xD;
&#xD;
                    -  Other INI1-negative or SMARCA4-deficient primary CNS malignant tumors (with&#xD;
                       PI approval)&#xD;
&#xD;
          -  All participants must have tumor assessment at original diagnosis or relapse showing&#xD;
             the following:&#xD;
&#xD;
               -  Loss of INI1 confirmed by immunohistochemistry (IHC), OR&#xD;
&#xD;
               -  Molecular confirmation of tumor bi-allelic SMARCB1 (INI1) loss or mutation when&#xD;
                  INI1 IHC is equivocal or unavailable&#xD;
&#xD;
               -  Loss of SMARCA4 confirmed by IHC or molecular confirmation of tumor bi-allelic&#xD;
                  SMARCA4 loss or mutation when SMARCA4 is equivocal or unavailable&#xD;
&#xD;
          -  Relapsed or refractory disease and no standard treatment options as determined by&#xD;
             locally or regionally available standards of care and treating physician's discretion&#xD;
&#xD;
          -  Measurable disease as defined by RECIST v1.1 (Stratum 1) or RANO criteria (Stratum 2)&#xD;
&#xD;
          -  Karnofsky performance status ≥ 50% for participants ≥16 years of age and Lansky&#xD;
             performance status ≥ 50% for participants &lt;16 years of age&#xD;
&#xD;
          -  Participants must have fully recovered from the acute toxic effects of all prior&#xD;
             anti-cancer therapy. Participants must meet the following minimum washout periods&#xD;
             prior to first day of study treatment:&#xD;
&#xD;
               -  Myelosuppressive chemotherapy: At least 14 days after the last dose of&#xD;
                  myelosuppressive chemotherapy&#xD;
&#xD;
               -  Radiotherapy&#xD;
&#xD;
                    -  At least 14 days after local palliative XRT (small port)&#xD;
&#xD;
                    -  At least 90 days must have elapsed after prior TBI, craniospinal XRT or if&#xD;
                       &gt;50% radiation of pelvis&#xD;
&#xD;
                    -  At least 42 days must have elapsed if other substantial BM radiation&#xD;
&#xD;
                    -  At least 42 days must have passed since last radionuclide therapy (e.g.&#xD;
                       samarium or radium)&#xD;
&#xD;
               -  Small molecule biologic therapy: At least 7 days following the last dose of a&#xD;
                  nonmonoclonal biologic agent&#xD;
&#xD;
               -  Monoclonal antibody: At least 21 days after the last dose&#xD;
&#xD;
               -  Myeloid growth factors: At least 14 days following the last dose of long-acting&#xD;
                  growth factor (e.g. Neulasta) or 7 days following short-acting growth factor&#xD;
&#xD;
               -  Stem Cell or Autologous T Cell Infusion: At least 42 days must have elapsed after&#xD;
                  stem cell or autologous T cell infusion&#xD;
&#xD;
          -  Participants must have adequate organ function as defined below&#xD;
&#xD;
               -  Bone Marrow Function&#xD;
&#xD;
                    -  Absolute neutrophil count ≥500/uL&#xD;
&#xD;
                    -  Platelets ≥50,000/uL and transfusion independent&#xD;
&#xD;
               -  Hepatic Function&#xD;
&#xD;
                    -  Total bilirubin ≤ 1.5 x upper limit of normal for age&#xD;
&#xD;
                    -  ALT (SGPT) ≤ 3 x upper limit of normal&#xD;
&#xD;
               -  Renal function&#xD;
&#xD;
                    -  A serum creatinine within protocol limits based on age/sex. OR&#xD;
&#xD;
                    -  Creatinine clearance ≥ 70 mL/min/1.73 m2 for participants with creatinine&#xD;
                       levels above institutional normal&#xD;
&#xD;
               -  Adequate Pulmonary Function Defined as: no evidence of dyspnea at rest, no&#xD;
                  exercise intolerance due to pulmonary insufficient and a pulse oximetry &gt; 92%&#xD;
                  while breathing room air&#xD;
&#xD;
               -  Adequate pancreatic function defined as serum lipase ≤ ULN at baseline&#xD;
&#xD;
               -  Negative B-HCG pregnancy test in females of childbearing potential (must be drawn&#xD;
                  within 24 hours prior to initial administration of nivolumab)&#xD;
&#xD;
               -  Women of childbearing potential (WOCBP) receiving nivolumab agree to adhere to&#xD;
                  contraception for a period of 5 months after the last dose of nivolumab. Men&#xD;
                  receiving nivolumab and who are sexually active with WOCBP will agree to adhere&#xD;
                  to contraception for a period of 7 months after the last dose of nivolumab.&#xD;
&#xD;
               -  Ability to understand and/or the willingness of the patient (or parent or legally&#xD;
                  authorized representative, if minor) to provide informed consent using an&#xD;
                  institutionally approved informed consent procedure.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants who are receiving any other investigational agents.&#xD;
&#xD;
          -  Participants must not be receiving concomitant systemic steroid medications The use of&#xD;
             physiologic doses of corticosteroids (up to 5 mg/m2/day prednisone equivalent) may be&#xD;
             approved after consultation with the PI (treatment with topical, inhaled or ophthalmic&#xD;
             corticosteroid is acceptable)&#xD;
&#xD;
          -  Participants with a known history of HIV, hepatitis B, and/or hepatitis C&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection or any other concurrent disease which in the judgment of the Investigator&#xD;
             would make the subject inappropriate for enrollment on this study&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or has current&#xD;
             pneumonitis&#xD;
&#xD;
          -  Has active autoimmune disease that has required systemic treatment in the past 12&#xD;
             months, or a documented history of clinically severe autoimmune disease, or a syndrome&#xD;
             that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or&#xD;
             resolved childhood asthma/atopy are exceptions. Intermittent use of bronchodilators or&#xD;
             local steroid injections are not excluded. Replacement therapy (e.g. thyroxine,&#xD;
             insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary&#xD;
             insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune&#xD;
             diagnoses not listed must be approved by the Principal Investigator.&#xD;
&#xD;
          -  Patients who have received prior solid organ transplantation are not eligible.&#xD;
&#xD;
          -  Pregnancy or Breast-Feeding. Pregnant or breast-feeding women will not be entered on&#xD;
             this study due to risks of fetal and teratogenic adverse events as there is yet no&#xD;
             available information regarding human fetal or teratogenic toxicities. Pregnancy tests&#xD;
             must be obtained in girls who are post-menarchal.&#xD;
&#xD;
          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or anti-CTLA4&#xD;
             agent or with an agent directed to another stimulatory or co-inhibitory T-cell&#xD;
             receptor (e.g. OX-40, CD137)&#xD;
&#xD;
          -  Participants who have received live / attenuated vaccine within 30 days of first dose&#xD;
             of study treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Suzanne Forrest, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Suzanne Forrest, MD</last_name>
    <phone>(617) 632-6443</phone>
    <email>suzanne_forrest@dfci.harvard.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>UCSF Benioff Children's Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alyssa Reddy, MD</last_name>
      <email>Alyssa.Reddy@ucsf.edu</email>
    </contact>
    <contact_backup>
      <last_name>Sunya Akhter</last_name>
      <email>Sunya.Akhter@ucsf.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Alyssa Reddy, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta-Egleston</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olivia Floyd</last_name>
      <email>Olivia.Floyd@choa.org</email>
    </contact>
    <investigator>
      <last_name>Thomas Cash, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta-Scottish Rite</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olivia Floyd</last_name>
      <email>olivia.floyd@choa.org</email>
    </contact>
    <investigator>
      <last_name>Thomas Cash, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gregory Cote, MD, PhD</last_name>
      <email>gcote@partners.org</email>
    </contact>
    <investigator>
      <last_name>Gregory Cote, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suzanne Forrest, MD</last_name>
      <phone>617-632-6443</phone>
    </contact>
    <investigator>
      <last_name>Suzanne Forrest</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suzanne Forrest, MD</last_name>
      <phone>617-632-6443</phone>
      <email>Suzanne_Forrest@dfci.harvard.edu</email>
    </contact>
    <contact_backup>
      <last_name>Jeffrey Czaplinski</last_name>
      <phone>617-632-5063</phone>
      <email>JeffreyT_Czaplinski@dfci.harvard.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Suzanne Forrest, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cassie Kline, MD</last_name>
      <email>klinec@chop.edu</email>
    </contact>
    <contact_backup>
      <last_name>Alyssa Ciampaglia</last_name>
      <email>ciampaglia@chop.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Cassie Kline, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Texas Children's Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joanna Yi, MD</last_name>
      <phone>832-824-6699</phone>
      <email>jsyi@texaschildrens.org</email>
    </contact>
    <contact_backup>
      <last_name>Julieta Simovich</last_name>
      <phone>(832) 824-4217</phone>
      <email>mjsimovi@texaschildrens.org</email>
    </contact_backup>
    <investigator>
      <last_name>Joanna Yi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>March 6, 2023</last_update_submitted>
  <last_update_submitted_qc>March 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Suzanne Forrest, MD</investigator_full_name>
    <investigator_title>Sponsor Investigator</investigator_title>
  </responsible_party>
  <keyword>Malignant Rhabdoid Tumor</keyword>
  <keyword>Rhabdoid Tumor of the Kidney</keyword>
  <keyword>Epithelioid Sarcoma</keyword>
  <keyword>Chordoma (poorly differentiated or de-differentiated)</keyword>
  <keyword>Atypical Teratoid/Rhabdoid Tumor</keyword>
  <keyword>INI1 negative tumors</keyword>
  <keyword>SMARCA4-deficient malignant tumors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Rhabdoid Tumor</mesh_term>
    <mesh_term>Chordoma</mesh_term>
    <mesh_term>Kidney Neoplasms</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>Yes</sharing_ipd>
    <ipd_description>The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data can be shared no earlier than 1 year following the date of publication</ipd_time_frame>
    <ipd_access_criteria>DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu</ipd_access_criteria>
  </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/NCT04416568
org study id: 20-041
nct id: NCT04416568
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This clinical trial is studying two immunotherapy drugs (nivolumab and ipilimumab) given
      together as a possible treatment for INI1-negative tumors.
This research study is a Phase II clinical trial, which tests the safety and effectiveness of
      an investigational drug or drug combination to learn whether the drug or drug combination
      works in treating a specific disease. "Investigational" means that the drug combination is
      being studied.

      The names of the study drugs involved in this study are:

        -  Nivolumab (OPDIVO)

        -  Ipilimumab (YERYOY)

      This trial is studying whether nivolumab and ipilimumab work to treat INI1-negative cancers.

      The U.S. Food and Drug Administration (FDA) has not approved combination nivolumab and
      ipilimumab for the specific diseases in this study but it has been approved for other
      diseases. Nivolumab and ipilimumab have been tested in children to find out a safe dose of
      this combination.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Overall Response Rate (Stratum 1)
time frame: 12 months
description: Based on Response Evaluation in Solid Tumors (RECIST) version 1.1
measure: Objective Overall Response Rate (Stratum 2)
time frame: 12 months
description: Based on Response Assessment in Neuro-Oncology (RANO) Criteria
measure: Progression-free survival (PFS)
time frame: 3 years
description: Time from study enrollment until the first occurrence of disease progression, relapse or death due to disease
measure: Overall survival (OS)
time frame: 3 years
description: Time from study enrollment until death from any cause
measure: Disease control rate at 12 months
time frame: 12 Months
description: The proportion of patients who are progression-free at 12 months
measure: Occurrence of toxicities (Grade 3-5 per CTCAE)
time frame: 13 months
description: Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0
arm group label: Solid Tumor (Stratum 1)
arm group type: Experimental
description: Patients will receive combination therapy with nivolumab at a predetermined dose and ipilimumab at a predetermined dose day 1 of a 21-day cycle for 4 cycles
Starting with cycle 5, patients will receive nivolumab monotherapy at a predetermined dose on day 1 and day 15 of a 28-day cycle
Patients with INI1-negative relapsed or refractory extracranial solid tumors
arm group label: CNS (Stratum 2)
arm group type: Experimental
description: Patients will receive combination therapy with nivolumab at a predetermined dose and ipilimumab at a predetermined dose day 1 of a 21-day cycle for 4 cycles
Starting with cycle 5, patients will receive nivolumab monotherapy at a predetermined dose on day 1 and day 15 of a 28-day cycle
Patients with INI1-negative relapsed or refractory CNS tumors
intervention type: Drug
intervention name: Nivolumab
description: Combination Therapy: Nivolumab at predetermined dosage day 1 of a 21-day cycle for 4 cycles.
Monotherapy: Starting with cycle 5 nivolumab at predetermined dosage on day 1 and day 15 of a 28-day cycle
arm group label: CNS (Stratum 2)
arm group label: Solid Tumor (Stratum 1)
other name: OPDIVO
intervention type: Drug
intervention name: Ipilimumab
description: Combination Therapy: Ipilimumab at predetermined dosage day 1 of a 21-day cycle for 4 cycles
arm group label: CNS (Stratum 2)
arm group label: Solid Tumor (Stratum 1)
other name: YERYOY
criteria: 
gender: All
minimum age: 6 Months
maximum age: 40 Years
healthy volunteers: No
last name: Suzanne Forrest, MD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
last name: Suzanne Forrest, MD
phone: (617) 632-6443
email: suzanne_forrest@dfci.harvard.edu
facility: 
status: Recruiting
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status: Recruiting
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country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Suzanne Forrest, MD
investigator title: Sponsor Investigator
mesh term: Neoplasms
mesh term: Sarcoma
mesh term: Rhabdoid Tumor
mesh term: Chordoma
mesh term: Kidney Neoplasms
mesh term: Nivolumab
mesh term: Ipilimumab
sharing ipd: Yes
ipd description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data can be shared no earlier than 1 year following the date of publication
ipd access criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu