<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/NCT04413123</url>
  </required_header>
  <id_info>
    <org_study_id>19-789</org_study_id>
    <nct_id>NCT04413123</nct_id>
  </id_info>
  <brief_title>Cabozantinib In Combo With NIVO + IPI In Advanced NCCRCC</brief_title>
  <official_title>A Phase 2 Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Advanced Non-Clear Cell Renal Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bradley A. McGregor, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Exelixis</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 will assess whether cabozantinib, nivolumab and ipilimumab in combination&#xD;
      are safe and effective in slowing down the growth of kidney cancer(renal cell carcinoma or&#xD;
      RCC) that has advanced or spread to other areas the body.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study involves an investigational drug combination not approved by the FDA (the&#xD;
      U.S. Food and Drug Administration) for your kidney cancer.&#xD;
&#xD;
      The names of the study drugs in this investigational combination are:&#xD;
&#xD;
        -  Cabozantinib&#xD;
&#xD;
        -  Nivolumab&#xD;
&#xD;
        -  Ipilimumab&#xD;
&#xD;
      The research study procedures include screening for eligibility, study treatment, participant&#xD;
      evaluations and safety follow-up visits, in addition to general health status follow-up after&#xD;
      study treatment.&#xD;
&#xD;
      It is expected that about 40 people will take part in this research study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 5, 2020</start_date>
  <completion_date type="Anticipated">December 20, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 20, 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>Overall Response Rate</measure>
    <time_frame>tart of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started up to 21 Months</time_frame>
    <description>Percent of patients who achieve overall response (CR or PR) by RECIST 1.1 will be summarized with 80% two-sided exact binomial confidence intervals (CI)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>first documentation of response, to the earlier of the first documentation of disease progression or death from any cause, and calculated for patients with a best confirmed response of CR up to 21 Months</time_frame>
    <description>will be estimated using the method of Kaplan-Meier, for all patients and by histology subtypes. M</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>trial treatment start to the earlier of progression or death due to any cause per investigator assessment. Participants alive without disease progression are censored at date of last disease evaluation up to 21 Months</time_frame>
    <description>the method of Kaplan-Meier, for all patients and by histology subtypes evaluation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>from trial treatment start to death due to any cause or censored at date last known alive up to 21 Months</time_frame>
    <description>the method of Kaplan-Meier, for all patients and by histology subtypes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>&quot;Number of Participants with TreatmentRelated Adverse Events as Assessed by CTCAE version 5.</measure>
    <time_frame>Baseline, day 1 of every cycle (21 days for first 4 cycles and then 28 days for each cycle tehreafter) and End of Treatment up 21 months</time_frame>
    <description>For toxicity reporting, all adverse events will be graded and analyzed using CTCAE version 5.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life- FKSI-19 Scale</measure>
    <time_frame>12 weeks for the first assessment, then every 8 weeks (+/- 7 days) for the first 6 months. Then take place every 12 weeks (+/- 7 days)</time_frame>
    <description>The Functional Assessment of Cancer Therapy-Kidney Symptom (FKSI-19) is a 19 item questionnaire with each item scored on a scale of 0-4 for a total score of 0-76 with higher scores indicating fewer symptom</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life-BFI Questionaire</measure>
    <time_frame>2 weeks for the first assessment, then every 8 weeks (+/- 7 days) for the first 6 months. Then take place every 12 weeks (+/- 7 days)</time_frame>
    <description>The Brief Fatigue Inventory (BFI) is a 9-item questionnaire with each item scored on a scale of 0-10.&#xD;
Scores are categorized as mild (1-3), moderate (4-6), or severe (7-10). A global fatigue score can be found by averaging the score obtained on each test item completed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>defined as the percentage of patients with partial (PR) or complete response (CR) as best overall response according to RECIST 1.1 by investigator assessment up to 21 Months</time_frame>
    <description>ORR by RECIST 1.1 according to histology subtypes (Papillary RCC versus other histology types) will be summarized with 80% two-sided exact CIs.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Papillary Renal Cell Carcinoma</condition>
  <condition>Unclassified Renal Cell Carcinoma</condition>
  <condition>Translocation Renal Cell Carcinoma</condition>
  <condition>Chromophobe Renal Cell Carcinoma</condition>
  <condition>Collecting Duct Renal Cell Carcinoma</condition>
  <condition>Renal Cell Carcinoma</condition>
  <condition>Unresectable Advanced Renal Cell Carcinoma</condition>
  <condition>Metastatic Ncc Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Cabozantinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible patients will be enrolled and receive treatment with&#xD;
Cycle 1-4 (cycles of 21 days)&#xD;
Cabozantinib predetermined protocol dosage po daily&#xD;
Nivolumab predetermined protocol dosage via IV every 3 weeks&#xD;
Ipilimumab predetermined protocol dosage via IV every 3 weeks&#xD;
After the first four cycles of therapy,&#xD;
Cabozantinib determined protocol dosage po daily&#xD;
Nivolumab predetermined protocol dosage via IV every 3 weeks (cycles of 28 days)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabozantinib</intervention_name>
    <description>Cabozantinib predetermined protocol dosage po daily</description>
    <arm_group_label>Cabozantinib</arm_group_label>
    <other_name>COMETRIQ™</other_name>
    <other_name>CABOMETYX™</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Nivolumab predetermined protocol dosage via IV every 3 weeks</description>
    <arm_group_label>Cabozantinib</arm_group_label>
    <other_name>Opdivo®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>Ipilimumab predetermined protocol dosage via IV every 3 weeks</description>
    <arm_group_label>Cabozantinib</arm_group_label>
    <other_name>Yervoy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  histologically or cytologically confirmed unresectable advanced or metastatic nccRCC,&#xD;
             including but not limited to:&#xD;
&#xD;
               -  Papillary RCC, any type&#xD;
&#xD;
               -  Unclassified RCC&#xD;
&#xD;
               -  Translocation RCC&#xD;
&#xD;
               -  Chromophobe RCC&#xD;
&#xD;
               -  Collecting duct RCC&#xD;
&#xD;
               -  Medullary RCC&#xD;
&#xD;
               -  Renal cell carcinoma with 80% or more sarcomatoid features on primary nephrectomy&#xD;
                  specimen or a biopsy&#xD;
&#xD;
               -  Other nccRCC histologies&#xD;
&#xD;
          -  Measurable disease as per RECIST 1.1. See Section 11 for the evaluation of measurable&#xD;
             disease.&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  ECOG performance status ≤1 (Karnofsky ≥70%, see Appendix A)&#xD;
&#xD;
          -  Participants must undergo fresh tumor biopsy after registration but prior to the start&#xD;
             of treatment unless medically unsafe or not feasible. If a fresh tumor biopsy is not&#xD;
             medically safe or not feasible, confirmation of the availability of archival tumor&#xD;
             tissue is required. For archival tissue, a recommended minimum of 20 unstained slides&#xD;
             should be obtained.&#xD;
&#xD;
          -  Normal organ and marrow function as defined below:&#xD;
&#xD;
               -  absolute neutrophil count ≥1,500/mcL&#xD;
&#xD;
               -  platelets ≥100,000/mcL&#xD;
&#xD;
               -  hemoglobin ≥9g/dL (transfusions allowed)&#xD;
&#xD;
               -  total bilirubin ≤2.0 x institutional upper limit of normal with the following&#xD;
                  exception: patients with known Gilbert disease should have a serum bilirubin ≤ 3&#xD;
                  x ULN&#xD;
&#xD;
          -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal with the following&#xD;
             exception: patients with known liver metastases should have AST and ALT ≤ 5 x ULN&#xD;
&#xD;
          -  creatinine clearance ≥30 mL/min/1.73 m2 according to the Cockcroft-Gault equation.&#xD;
&#xD;
          -  Normal coagulation INR ≤ 1.5&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for&#xD;
             5 months after the duration of study participation. Should a woman become pregnant or&#xD;
             suspect she is pregnant while she or her partner is participating in this study, she&#xD;
             should inform her treating physician immediately. Men treated or enrolled on this&#xD;
             protocol must also agree to use adequate contraception prior to the study, for the&#xD;
             duration of study participation, and 7 months after completion of cabozantinib,&#xD;
             nivolumab or ipilimumab administration.&#xD;
&#xD;
          -  Ability to understand and willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Patients could be untreated or have received prior lines of therapies. Patients who&#xD;
        receive prior therapy may receive only one VEGF based therapy. A combination therapy (e.g.&#xD;
&#xD;
        lenvatinib+everolimus) is considered 1 line of therapy.&#xD;
&#xD;
          -  Previous therapy with CD137 agonists and immune checkpoint inhibitors, including but&#xD;
             not limited to inhibitors of the PD-1/PD-L1 and/or CTLA-4 axes. Previous treatment&#xD;
             with IFNα or IL-2 is allowed if received &gt; 4 weeks from enrollment.&#xD;
&#xD;
          -  Treatment with small molecule tyrosine kinase inhibitors within 2 weeks of enrollment,&#xD;
             or any other anticancer agent within 4 weeks of enrollment.&#xD;
&#xD;
          -  Prior therapy with cabozantinib&#xD;
&#xD;
          -  Patients receiving any other therapeutic investigational agents.&#xD;
&#xD;
          -  Treatment with hydroxychloroquine within two weeks of treatment start.&#xD;
&#xD;
          -  Radiotherapy for nccRCC within 14 days of first study treatment with the exception of&#xD;
             a single fraction of radiation administered for palliation of symptoms.&#xD;
&#xD;
          -  Untreated brain metastases. Patients might be included if they underwent radiation&#xD;
             therapy or surgery at least 4 weeks prior enrollment. Stability of the central nervous&#xD;
             system disease should be confirmed by brain MRI or CT-scan or as determined by&#xD;
             treating investigator. Patients should not be receiving prednisone dose &gt;10 mg/d at&#xD;
             C1D1.&#xD;
&#xD;
          -  Other malignancy diagnosed within 2 years of first study treatment unless negligible&#xD;
             risk of metastases or death (included but not limited to carcinoma in situ of the&#xD;
             cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal&#xD;
             carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma, or other&#xD;
             malignancy not deemed to impact patients 5-year life expectancy).&#xD;
&#xD;
          -  Significant cardiovascular disorders including:&#xD;
&#xD;
               -  Significant cardiovascular disease including dyspnea of New York Heart&#xD;
                  Association (NYHA) class II or greater, myocardial infarction within the previous&#xD;
                  3 months of first study treatment, unstable arrhythmias, unstable angina.&#xD;
                  Patients with known coronary artery disease or congestive heart failure not&#xD;
                  meeting the above criteria, or left ventricular ejection fraction &lt; 50%, must be&#xD;
                  on a stable and optimized in the opinion of the treating physician, in&#xD;
                  consultation with a cardiologist when appropriate.&#xD;
&#xD;
               -  Uncontrolled hypertension (defined as systolic blood pressure &gt; 150 mmHg and/or&#xD;
                  diastolic blood pressure &gt; 100 mmHg). Anti-hypertensive therapy is allowed.&#xD;
&#xD;
               -  Personal history of hypertensive crisis or hypertensive encephalopathy within the&#xD;
                  previous 3 months of registration.&#xD;
&#xD;
               -  Personal history of stroke or transient ischemic attack within 3 months of&#xD;
                  registration.&#xD;
&#xD;
               -  Significant vascular disease, such as but not limited to aortic aneurysm&#xD;
                  requiring surgical repair or recent peripheral arterial thrombosis, within 6&#xD;
                  months of registration.&#xD;
&#xD;
          -  Corrected QT interval calculated by the Fridericia formula (QTcF) &gt; 500 ms per&#xD;
             electrocardiogram (ECG). Furthermore, subjects with a history of additional risk&#xD;
             factors for torsades de pointes (eg, long QT syndrome) are also excluded.&#xD;
&#xD;
          -  Known history of severe allergic reactions attributed to compounds of similar chemical&#xD;
             or biologic composition human antibodies, or known hypersensitivity to any component&#xD;
             of cabozantinib, nivolumab or ipilimumab products.&#xD;
&#xD;
          -  Systemic immunosuppressive medications including but not limited to: Corticosteroids&#xD;
             at a dose &gt; 10mg equivalent prednisone daily, cyclosporin, azathioprine, methotrexate,&#xD;
             thalidomide, anti-tumor necrosis factor (TNF) agents, hydroxychloroquine, within 2&#xD;
             weeks of first study dose.&#xD;
&#xD;
               -  Patients who have received acute, low-dose systemic immunosuppressant medications&#xD;
                  may be enrolled.&#xD;
&#xD;
               -  Patients with adrenal insufficiency on physiologic replacement doses of steroids&#xD;
                  may be enrolled.&#xD;
&#xD;
               -  The use of inhaled, topical, intraocular, or intraarticular corticosteroids or&#xD;
                  mineralocorticoids are allowed&#xD;
&#xD;
          -  Prior allogenic stem cell or solid organ transplant.&#xD;
&#xD;
          -  Personal history of autoimmune disease including: myasthenia gravis, myositis,&#xD;
             autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory&#xD;
             bowel disease, vascular thrombosis associated with anti-phospholipid syndrome,&#xD;
             Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple&#xD;
             sclerosis, type I diabetes mellitus, vasculitis, or glomerulonephritis. Patients with&#xD;
             a history of autoimmune-related hypothyroidism on thyroid replacement hormone, or&#xD;
             those with autoimmune dermatologic conditions not requiring the use of prednisone &gt; 10&#xD;
             mg or equivalent are eligible.&#xD;
&#xD;
          -  History of idiopathic pulmonary fibrosis, organized pneumonia, or evidence of active&#xD;
             pneumonitis on screening imaging CT of the chest. History of radiation pneumonitis in&#xD;
             the radiation field is permitted.&#xD;
&#xD;
          -  History of following infectious diseases:&#xD;
&#xD;
               -  Active or chronic hepatitis B (defined as having a positive hepatitis B surface&#xD;
                  antigen [HBsAg] test at screening).&#xD;
&#xD;
               -  Active hepatitis C infection. Patients with positive hepatitis C antibody test&#xD;
                  are eligible if PCR is negative for hepatitis C viral DNA.&#xD;
&#xD;
               -  Infection requiring therapeutic oral or IV anti-microbials within 2 weeks of&#xD;
                  first study treatment. Patients receiving routine antimicrobial prophylaxis for&#xD;
                  dental procedures are eligible.&#xD;
&#xD;
               -  Known positive test for HIV.&#xD;
&#xD;
          -  Administration of a live, attenuated vaccine within 3 weeks for first study treatment.&#xD;
&#xD;
          -  Bleeding diathesis, or significant coagulopathy in the absence of therapeutic&#xD;
             anticoagulation.&#xD;
&#xD;
          -  Use of strong inhibitors and inducers of CYP3A4&#xD;
&#xD;
          -  Significant bleeding, including but not limited to hematemesis, hematuria, hemoptysis&#xD;
             of &gt; 0.5 teaspoon (2.5 mL), within 3 months before registration.&#xD;
&#xD;
          -  Invasion of major pulmonary blood vessels. A discussion with PI may be needed if&#xD;
             invading lesions are suspected.&#xD;
&#xD;
          -  Concomitant use of dipyramidole, ticlopidine, clopidogrel, cilostazol is excluded.&#xD;
             Aspirin (≤ 325 mg per day) is allowed. Prophylactic anticoagulation with oral or&#xD;
             parenteral anticoagulants for the patency of venous access devices or other&#xD;
             indications is allowed.&#xD;
&#xD;
        Therapeutic use of low-molecular weight heparin (such as enoxaparin) and subcutaneous or&#xD;
        oral Factor Xa inhibitors are allowed. Use of warfarin is prohibited.&#xD;
&#xD;
          -  Significant GI conditions at risk of perforation or bleeding, including but not&#xD;
             limited to:&#xD;
&#xD;
               -  Active GI obstruction or requirement of routine parenteral nutrition or tube&#xD;
                  feedings.&#xD;
&#xD;
               -  Personal history of abdominal or tracheoesophageal fistula or GI perforation&#xD;
                  within 6 months of registration.&#xD;
&#xD;
               -  Evidence of abdominal free air not explained by paracentesis or recent surgical&#xD;
                  procedure.&#xD;
&#xD;
               -  Serious, non-healing or dehiscing wound or active ulcer.&#xD;
&#xD;
          -  Major surgical procedure to include major dental, oral or maxillofacial procedures&#xD;
             within 14 days of first study treatment.&#xD;
&#xD;
          -  Proteinuria as demonstrated by &gt; 1.5 gram of protein in a 24-hour urine collection.&#xD;
             All patients with ≥ 2+ protein on urinalysis must undergo 24-hour urine collection for&#xD;
             protein.&#xD;
&#xD;
          -  Unable to swallow pills.&#xD;
&#xD;
          -  Malabsorption syndrome.&#xD;
&#xD;
          -  Inability to receive IV medications&#xD;
&#xD;
          -  Pregnant or lactating women.&#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>Bradley McGregor, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Bradley McGregor, MD</last_name>
    <phone>(617) 632-1914</phone>
    <email>Bmcgregor@partners.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David F McDermott, MD</last_name>
      <phone>617-632-9250</phone>
    </contact>
    <investigator>
      <last_name>David F McDermott, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Brigham &amp; Woman's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Bradley McGregor, MD</last_name>
    </contact>
    <investigator>
      <last_name>Bradley McGregor, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Bradley McGregor, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hans Hammers, M.D., PhD</last_name>
      <phone>214-648-4180</phone>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>March 26, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Bradley A. McGregor, MD</investigator_full_name>
    <investigator_title>Sponsor Investigator</investigator_title>
  </responsible_party>
  <keyword>Papillary Renal Cell Carcinoma</keyword>
  <keyword>Unclassified Renal Cell Carcinoma</keyword>
  <keyword>Translocation Renal Cell Carcinoma</keyword>
  <keyword>Chromophobe Renal Cell Carcinoma</keyword>
  <keyword>Collecting duct Renal Cell Carcinoma</keyword>
  <keyword>Renal Cell Carcinoma</keyword>
  <keyword>Unresectable Advanced Renal Cell Carcinoma</keyword>
  <keyword>Metastatic ncc Renal Cell Carcinoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</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>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/NCT04413123
org study id: 19-789
nct id: NCT04413123
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This research study will assess whether cabozantinib, nivolumab and ipilimumab in combination
      are safe and effective in slowing down the growth of kidney cancer(renal cell carcinoma or
      RCC) that has advanced or spread to other areas the body.
This research study involves an investigational drug combination not approved by the FDA (the
      U.S. Food and Drug Administration) for your kidney cancer.

      The names of the study drugs in this investigational combination are:

        -  Cabozantinib

        -  Nivolumab

        -  Ipilimumab

      The research study procedures include screening for eligibility, study treatment, participant
      evaluations and safety follow-up visits, in addition to general health status follow-up after
      study treatment.

      It is expected that about 40 people will take part in this research study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate
time frame: tart of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started up to 21 Months
description: Percent of patients who achieve overall response (CR or PR) by RECIST 1.1 will be summarized with 80% two-sided exact binomial confidence intervals (CI)
measure: Duration of response (DOR)
time frame: first documentation of response, to the earlier of the first documentation of disease progression or death from any cause, and calculated for patients with a best confirmed response of CR up to 21 Months
description: will be estimated using the method of Kaplan-Meier, for all patients and by histology subtypes. M
measure: Progression-free survival (PFS)
time frame: trial treatment start to the earlier of progression or death due to any cause per investigator assessment. Participants alive without disease progression are censored at date of last disease evaluation up to 21 Months
description: the method of Kaplan-Meier, for all patients and by histology subtypes evaluation.
measure: Overall survival (OS)
time frame: from trial treatment start to death due to any cause or censored at date last known alive up to 21 Months
description: the method of Kaplan-Meier, for all patients and by histology subtypes
measure: "Number of Participants with TreatmentRelated Adverse Events as Assessed by CTCAE version 5.
time frame: Baseline, day 1 of every cycle (21 days for first 4 cycles and then 28 days for each cycle tehreafter) and End of Treatment up 21 months
description: For toxicity reporting, all adverse events will be graded and analyzed using CTCAE version 5.
measure: Quality of life- FKSI-19 Scale
time frame: 12 weeks for the first assessment, then every 8 weeks (+/- 7 days) for the first 6 months. Then take place every 12 weeks (+/- 7 days)
description: The Functional Assessment of Cancer Therapy-Kidney Symptom (FKSI-19) is a 19 item questionnaire with each item scored on a scale of 0-4 for a total score of 0-76 with higher scores indicating fewer symptom
measure: Quality of life-BFI Questionaire
time frame: 2 weeks for the first assessment, then every 8 weeks (+/- 7 days) for the first 6 months. Then take place every 12 weeks (+/- 7 days)
description: The Brief Fatigue Inventory (BFI) is a 9-item questionnaire with each item scored on a scale of 0-10.
Scores are categorized as mild (1-3), moderate (4-6), or severe (7-10). A global fatigue score can be found by averaging the score obtained on each test item completed
measure: Objective response rate (ORR)
time frame: defined as the percentage of patients with partial (PR) or complete response (CR) as best overall response according to RECIST 1.1 by investigator assessment up to 21 Months
description: ORR by RECIST 1.1 according to histology subtypes (Papillary RCC versus other histology types) will be summarized with 80% two-sided exact CIs.
arm group label: Cabozantinib
arm group type: Experimental
description: Eligible patients will be enrolled and receive treatment with
Cycle 1-4 (cycles of 21 days)
Cabozantinib predetermined protocol dosage po daily
Nivolumab predetermined protocol dosage via IV every 3 weeks
Ipilimumab predetermined protocol dosage via IV every 3 weeks
After the first four cycles of therapy,
Cabozantinib determined protocol dosage po daily
Nivolumab predetermined protocol dosage via IV every 3 weeks (cycles of 28 days)
intervention type: Drug
intervention name: Cabozantinib
description: Cabozantinib predetermined protocol dosage po daily
arm group label: Cabozantinib
other name: COMETRIQ™
other name: CABOMETYX™
intervention type: Drug
intervention name: Nivolumab
description: Nivolumab predetermined protocol dosage via IV every 3 weeks
arm group label: Cabozantinib
other name: Opdivo®
intervention type: Drug
intervention name: Ipilimumab
description: Ipilimumab predetermined protocol dosage via IV every 3 weeks
arm group label: Cabozantinib
other name: Yervoy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bradley McGregor, MD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
last name: Bradley McGregor, MD
phone: (617) 632-1914
email: Bmcgregor@partners.org
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Bradley A. McGregor, MD
investigator title: Sponsor Investigator
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
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: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu