<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/NCT03246958</url>
  </required_header>
  <id_info>
    <org_study_id>17-255</org_study_id>
    <nct_id>NCT03246958</nct_id>
  </id_info>
  <brief_title>Nivolumab Plus Ipilimumab in Thyroid Cancer</brief_title>
  <official_title>A Phase 2 Study of Nivolumab Plus Ipilimumab in RAI Refractory, Aggressive Thyroid Cancer With Exploratory Cohorts in Medullary and Anaplastic Thyroid Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</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 research study is studying nivolumab, an investigational drug, in combination with&#xD;
      ipilimumab, also an investigational drug, as a possible treatment for thyroid cancer.&#xD;
&#xD;
      The drugs involved in this study are:&#xD;
&#xD;
        -  Nivolumab (Opdivo™)&#xD;
&#xD;
        -  Ipilimumab (Yervoy™)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is a Phase 2 clinical trial. Phase 2 clinical trials test the safety and&#xD;
      effectiveness of an investigational intervention to learn whether the intervention works in&#xD;
      treating a specific disease. &quot;Investigational&quot; means that the intervention is being studied.&#xD;
&#xD;
      The purpose of this study is to evaluate effectiveness (how well the drug/s work) of&#xD;
      nivolumab combined with ipilimumab.&#xD;
&#xD;
      Nivolumab and ipilimumab are types of immunotherapy. Immunotherapy works by encouraging the&#xD;
      body's own immune system to attack cancer cells. Nivolumab has been approved by the US Food&#xD;
      and Drug Administration (FDA) for the treatment of metastatic melanoma (a type of skin&#xD;
      cancer), and specific types of previously treated advanced lung and kidney cancers.&#xD;
      Ipilimumab is approved by the FDA for the treatment of metastatic melanoma.&#xD;
&#xD;
      The combination of nivolumab and ipilimumab is now FDA approved as treatment for patients&#xD;
      with metastatic melanoma. However, the use of nivolumab as well as ipilimumab alone or in&#xD;
      combination for the treatment of patients with thyroid cancer is not approved&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 20, 2017</start_date>
  <completion_date type="Anticipated">March 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Radiographic Response Rate</measure>
    <time_frame>2 years</time_frame>
    <description>Radiographic Response Rate to the investigational treatment, as determined by RECIST v1.1 (PR+CR)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>2 years</time_frame>
    <description>The time from randomization to progression or death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>2 years</time_frame>
    <description>The time from randomization to death or date last known alive</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tolerability</measure>
    <time_frame>2 years</time_frame>
    <description>Treatment-Emergent Adverse Events (frequency and grade of adverse events)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">53</enrollment>
  <condition>Thyroid Cancer</condition>
  <arm_group>
    <arm_group_label>Nivolumab alone for two weeks</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ipilimumab will be administered via IV infusion, starting two weeks after Nivolumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ipilimumab alone for two weeks</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nivolumab will be administered via IV infusion, starting two weeks after Ipilimumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Ipilimumab are types of immunotherapy Immunotherapy works by encouraging the body's own immune system to attack cancer cells.</description>
    <arm_group_label>Ipilimumab alone for two weeks</arm_group_label>
    <arm_group_label>Nivolumab alone for two weeks</arm_group_label>
    <other_name>Opdivo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>Nivolumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells.</description>
    <arm_group_label>Ipilimumab alone for two weeks</arm_group_label>
    <arm_group_label>Nivolumab alone for two weeks</arm_group_label>
    <other_name>Yervoy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion&#xD;
&#xD;
          -  Metastatic, RAI refractory, differentiated thyroid cancer (including papillary and&#xD;
             follicular thyroid cancer and their sub-types such as Hurthle cell thyroid cancer as&#xD;
             well as poorly differentiated thyroid cancer), with progression within 13 months prior&#xD;
             to study registration. RAI refractoriness is defined as absence of uptake of RAI on&#xD;
             either a low-dose diagnostic test or a post-treatment RAI scan in measurable lesions&#xD;
             or radiographic progression of disease within 12 months of the last course of RAI&#xD;
             treatment despite the recorded uptake of RAI with that previous therapy or having a&#xD;
             cumulative lifetime administered dose of greater than 600mCi.&#xD;
&#xD;
          -  Exploratory cohort: incurable medullary thyroid cancer with prior tyrosine kinase&#xD;
             inhibitor (TKI) failure and progression within 13 months prior to enrollment (10&#xD;
             patients) and anaplastic thyroid cancer (7 patients)&#xD;
&#xD;
          -  Any number of lines of prior treatment are allowed&#xD;
&#xD;
          -  Any line of prior treatment for patients under 65y, over 65y must have at least one&#xD;
             prior line of TKI treatment&#xD;
&#xD;
          -  Age 18 years or older&#xD;
&#xD;
          -  ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)&#xD;
&#xD;
          -  Participants must have normal organ and marrow function as defined below:&#xD;
&#xD;
          -  Screening laboratory values must meet the following criteria and should be obtained&#xD;
             within 21 days prior to randomization/registration&#xD;
&#xD;
               -  WBC ≥ 2000/μL&#xD;
&#xD;
               -  Neutrophils ≥ 1500/μL&#xD;
&#xD;
               -  Platelets ≥ 100 x103/μL&#xD;
&#xD;
               -  Hemoglobin &gt; 9.0 g/dL&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using&#xD;
                  the Cockcroft-Gault formula below):&#xD;
&#xD;
               -  Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in&#xD;
                  mg/dL&#xD;
&#xD;
               -  Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in&#xD;
                  mg/dL&#xD;
&#xD;
               -  AST/ALT ≤ 3 x ULN&#xD;
&#xD;
               -  Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have&#xD;
                  total bilirubin &lt; 3.0 mg/dL)&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP) must use appropriate method(s) of&#xD;
             contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30&#xD;
             days plus the time required for nivolumab to undergo five half-lives) after the last&#xD;
             dose of investigational drug&#xD;
&#xD;
          -  Women of childbearing potential must have a negative serum or urine pregnancy test&#xD;
             (minimum sensitivity 25 iu/l or equivalent units of hcg) within 24 hours of the first&#xD;
             dose of the study drug&#xD;
&#xD;
          -  Women of childbearing potential&quot; is defined as any female who has experienced menarche&#xD;
             and who has not undergone surgical sterilization (hysterectomy or bilateral&#xD;
             oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12&#xD;
             months of amenorrhea in a woman over 45 in the absence of other biological or&#xD;
             physiological causes. In addition, women under the age of 55 must have a documented&#xD;
             serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.&#xD;
&#xD;
          -  Men who are sexually active with WOCBP must use any contraceptive method with a&#xD;
             failure rate of less than 1% per year Men receiving nivolumab and who are sexually&#xD;
             active with WOCBP will be instructed to adhere to contraception for a period of 31&#xD;
             weeks after the last dose of investigational product Women who are not of childbearing&#xD;
             potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men&#xD;
             do not require contraception&#xD;
&#xD;
        Exclusion&#xD;
&#xD;
          -  Patients should be excluded if they have an active, known or suspected autoimmune&#xD;
             disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes&#xD;
             mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone&#xD;
             replacement, psoriasis not requiring systemic treatment, or conditions not expected to&#xD;
             recur in the absence of an external trigger&#xD;
&#xD;
          -  Patients should be excluded if they have a condition requiring systemic treatment with&#xD;
             either corticosteroids (&gt; 10 mg daily prednisone equivalents) or other&#xD;
             immunosuppressive medications within 14 days of study drug administration. Inhaled or&#xD;
             topical steroids and adrenal replacement doses &gt; 10 mg daily prednisone equivalents&#xD;
             are permitted in the absence of active autoimmune disease.&#xD;
&#xD;
          -  As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab&#xD;
             combinations, drugs with a predisposition to hepatoxicity should be used with caution&#xD;
             in patients treated with nivolumab-containing regimen.&#xD;
&#xD;
          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for&#xD;
             nitrosoureas or mitomycin C) prior to entering the study or those who have not&#xD;
             recovered from adverse events due to agents administered more than 4 weeks earlier.&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents.&#xD;
&#xD;
          -  Patients with activebrain metastases should be excluded from this clinical trial&#xD;
             because of their poor prognosis and because they often develop progressive neurologic&#xD;
             dysfunction that would confound the evaluation of neurologic and other adverse events.&#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;
      </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>Kartik Sehgal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2017</study_first_posted>
  <last_update_submitted>February 18, 2022</last_update_submitted>
  <last_update_submitted_qc>February 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Kartik Sehgal</investigator_full_name>
    <investigator_title>Kartik Sehgal, MD</investigator_title>
  </responsible_party>
  <keyword>Thyroid Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thyroid Neoplasms</mesh_term>
    <mesh_term>Thyroid Diseases</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>No</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/NCT03246958
org study id: 17-255
nct id: NCT03246958
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This research study is studying nivolumab, an investigational drug, in combination with
      ipilimumab, also an investigational drug, as a possible treatment for thyroid cancer.

      The drugs involved in this study are:

        -  Nivolumab (Opdivo™)

        -  Ipilimumab (Yervoy™)
This research study is a Phase 2 clinical trial. Phase 2 clinical trials test the safety and
      effectiveness of an investigational intervention to learn whether the intervention works in
      treating a specific disease. "Investigational" means that the intervention is being studied.

      The purpose of this study is to evaluate effectiveness (how well the drug/s work) of
      nivolumab combined with ipilimumab.

      Nivolumab and ipilimumab are types of immunotherapy. Immunotherapy works by encouraging the
      body's own immune system to attack cancer cells. Nivolumab has been approved by the US Food
      and Drug Administration (FDA) for the treatment of metastatic melanoma (a type of skin
      cancer), and specific types of previously treated advanced lung and kidney cancers.
      Ipilimumab is approved by the FDA for the treatment of metastatic melanoma.

      The combination of nivolumab and ipilimumab is now FDA approved as treatment for patients
      with metastatic melanoma. However, the use of nivolumab as well as ipilimumab alone or in
      combination for the treatment of patients with thyroid cancer is not approved
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Radiographic Response Rate
time frame: 2 years
description: Radiographic Response Rate to the investigational treatment, as determined by RECIST v1.1 (PR+CR)
measure: Progression Free Survival
time frame: 2 years
description: The time from randomization to progression or death due to any cause
measure: Overall Survival
time frame: 2 years
description: The time from randomization to death or date last known alive
measure: Tolerability
time frame: 2 years
description: Treatment-Emergent Adverse Events (frequency and grade of adverse events)
arm group label: Nivolumab alone for two weeks
arm group type: Experimental
description: Ipilimumab will be administered via IV infusion, starting two weeks after Nivolumab
arm group label: Ipilimumab alone for two weeks
arm group type: Experimental
description: Nivolumab will be administered via IV infusion, starting two weeks after Ipilimumab
intervention type: Drug
intervention name: Nivolumab
description: Ipilimumab are types of immunotherapy Immunotherapy works by encouraging the body's own immune system to attack cancer cells.
arm group label: Ipilimumab alone for two weeks
arm group label: Nivolumab alone for two weeks
other name: Opdivo
intervention type: Drug
intervention name: Ipilimumab
description: Nivolumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells.
arm group label: Ipilimumab alone for two weeks
arm group label: Nivolumab alone for two weeks
other name: Yervoy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kartik Sehgal, MD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Kartik Sehgal
investigator title: Kartik Sehgal, MD
mesh term: Thyroid Neoplasms
mesh term: Thyroid Diseases
mesh term: Nivolumab
mesh term: Ipilimumab
sharing ipd: No