<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/NCT01709435</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2012-01890</org_study_id>
    <secondary_id>NCI-2012-01890</secondary_id>
    <secondary_id>P121149</secondary_id>
    <secondary_id>COG-ADVL1211</secondary_id>
    <secondary_id>NCI-2013-01571</secondary_id>
    <secondary_id>CDR0000741914</secondary_id>
    <secondary_id>ADVL1211</secondary_id>
    <secondary_id>ADVL1211</secondary_id>
    <secondary_id>UM1CA097452</secondary_id>
    <nct_id>NCT01709435</nct_id>
  </id_info>
  <brief_title>Cabozantinib S-Malate in Treating Younger Patients With Recurrent or Refractory Solid Tumors</brief_title>
  <official_title>A Phase 1 Study of XL184 (Cabozantinib) in Children and Adolescents With Recurrent or Refractory Solid Tumors, Including CNS Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the side effects and best dose of cabozantinib S-malate in&#xD;
      treating younger patients with solid tumors that have come back or no longer respond to&#xD;
      treatment. Cabozantinib S-malate may stop the growth of tumor cells by blocking some of the&#xD;
      enzymes needed for cell growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of XL184&#xD;
      (cabozantinib) (cabozantinib S-malate) administered orally to children with refractory solid&#xD;
      tumors including central nervous system (CNS) tumors.&#xD;
&#xD;
      II. To define and describe the toxicities of XL184 (cabozantinib) administered on this&#xD;
      schedule.&#xD;
&#xD;
      III. To characterize the pharmacokinetics of XL184 (cabozantinib) in children with refractory&#xD;
      solid tumors.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To preliminarily define the antitumor activity of XL184 (cabozantinib) within the confines&#xD;
      of a phase 1 study.&#xD;
&#xD;
      II. To assess the biologic activity of XL184 (cabozantinib). III. To assess the biomarker&#xD;
      response (carcinoembryonic antigen [CEA] and calcitonin) in patients with medullary thyroid&#xD;
      cancer treated with XL184.&#xD;
&#xD;
      IV. To evaluate overall survival from study entry through a five-year follow-up period.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study. (Complete as of 4/16/2014)&#xD;
&#xD;
      Patients receive cabozantinib S-malate orally (PO) once daily (QD) on days 1-28. Courses&#xD;
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days, 6 months, and then&#xD;
      annually for up to 60 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 14, 2012</start_date>
  <completion_date type="Actual">December 31, 2019</completion_date>
  <primary_completion_date type="Actual">December 31, 2018</primary_completion_date>
  <phase>Phase 1</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>Maximum tolerated dose (MTD) and/or recommended phase 2 dose of cabozantinib S-malate</measure>
    <time_frame>28 days</time_frame>
    <description>Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) parameters of cabozantinib S-malate including systemic exposure and drug clearance</measure>
    <time_frame>Course 1, day 1 (pre-dose and 4 hours post dose), course 1 day 21 (+/- 2 days) (pre-dose, 2, 4, 8 and 24 hours post dose), course 3 day 1 (pre-dose)</time_frame>
    <description>Will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease response</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will be assessed according to Response Evaluation Criteria in Solid Tumors 1.1 criteria and reported descriptively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>OS will also be assessed and summarized using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Recurrent Malignant Solid Neoplasm</condition>
  <condition>Recurrent Melanoma</condition>
  <condition>Recurrent Primary Central Nervous System Neoplasm</condition>
  <condition>Recurrent Thyroid Gland Carcinoma</condition>
  <condition>Refractory Malignant Solid Neoplasm</condition>
  <condition>Refractory Primary Central Nervous System Neoplasm</condition>
  <condition>Thyroid Gland Medullary Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (cabozantinib S-malate)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive cabozantinib S-malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabozantinib S-malate</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (cabozantinib S-malate)</arm_group_label>
    <other_name>BMS-907351</other_name>
    <other_name>Cabometyx</other_name>
    <other_name>Cometriq</other_name>
    <other_name>XL-184</other_name>
    <other_name>XL184</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (cabozantinib S-malate)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (cabozantinib S-malate)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have a body surface area &gt;= 0.44 m^2 when enrolling on dose level -1;&#xD;
             patients must have a body surface area &gt;= 0.35 m^2 when enrolling on dose level 1, 2,&#xD;
             or 3&#xD;
&#xD;
          -  PART A: Patients with relapsed or refractory solid tumors (excluding medullary thyroid&#xD;
             cancer) including CNS tumors and malignant melanoma are eligible; patients must have&#xD;
             had histologic verification of malignancy at original diagnosis or relapse except in&#xD;
             patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with&#xD;
             pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers&#xD;
             including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)&#xD;
&#xD;
          -  Part B: Patients with medullary thyroid cancer (MTC), with or without bone marrow&#xD;
             involvement, will be eligible for Part B; these patients will be enrolled at dose&#xD;
             level 2, the recommended phase 2 dose determined in the dose escalation part of the&#xD;
             study&#xD;
&#xD;
          -  Patients must have either measurable or evaluable disease&#xD;
&#xD;
          -  Patient's current disease state must be one for which there is no known curative&#xD;
             therapy or therapy proven to prolong survival with an acceptable quality of life&#xD;
&#xD;
          -  Karnofsky &gt;= 50% for patients &gt; 16 years of age and Lansky &gt;= 50 for patients =&lt; 16&#xD;
             years of age&#xD;
&#xD;
               -  Note: neurologic deficits in patients with CNS tumors must have been relatively&#xD;
                  stable for at least 7 days prior to study enrollment; patients who are unable to&#xD;
                  walk because of paralysis, but who are up in a wheelchair, will be considered&#xD;
                  ambulatory for the purpose of assessing the performance score&#xD;
&#xD;
          -  Patients must have fully recovered from the acute toxic effects of all prior&#xD;
             anti-cancer chemotherapy:&#xD;
&#xD;
               -  Myelosuppressive chemotherapy: at least 21 days after the last dose of&#xD;
                  myelosuppressive chemotherapy (42 days if prior nitrosourea)&#xD;
&#xD;
               -  Hematopoietic growth factors: at least 14 days after the last dose of a&#xD;
                  long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth&#xD;
                  factor; for agents that have known adverse events occurring beyond 7 days after&#xD;
                  administration, this period must be extended beyond the time during which adverse&#xD;
                  events are known to occur; the duration of this interval must be discussed with&#xD;
                  the study chair&#xD;
&#xD;
               -  Biologic (anti-neoplastic agent): at least 7 days after the last dose of a&#xD;
                  biologic agent; for agents that have known adverse events occurring beyond 7 days&#xD;
                  after administration, this period must be extended beyond the time during which&#xD;
                  adverse events are known to occur; the duration of this interval must be&#xD;
                  discussed with the study chair&#xD;
&#xD;
               -  Immunotherapy: at least 42 days after the completion of any type of&#xD;
                  immunotherapy, e.g. tumor vaccines&#xD;
&#xD;
               -  Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose&#xD;
                  of a monoclonal antibody&#xD;
&#xD;
               -  Radiation therapy (XRT): at least 14 days after local palliative XRT (small&#xD;
                  port); at least 150 days must have elapsed if prior total-body irradiation (TBI),&#xD;
                  craniospinal XRT or if &gt;= 50% radiation of pelvis; at least 42 days must have&#xD;
                  elapsed if other substantial bone marrow (BM) radiation&#xD;
&#xD;
               -  Stem cell infusion without TBI: no evidence of active graft versus (vs.) host&#xD;
                  disease and at least 56 days must have elapsed after transplant or stem cell&#xD;
                  infusion&#xD;
&#xD;
          -  For patients with solid tumors without known bone marrow involvement:&#xD;
&#xD;
          -  Peripheral absolute neutrophil count (ANC) &gt;= 1000/mm^3&#xD;
&#xD;
          -  Platelet count &gt;= 100,000/mm^3 (transfusion independent, defined as not receiving&#xD;
             platelet transfusions for at least 7 days prior to enrollment)&#xD;
&#xD;
          -  Patients with known bone marrow metastatic disease will be eligible for study provided&#xD;
             they meet the blood counts (may receive transfusions provided they are not known to be&#xD;
             refractory to red cell or platelet transfusions); these patients will not be evaluable&#xD;
             for hematologic toxicity; at least 5 of every cohort of 6 patients with a solid tumor&#xD;
             must be evaluable for hematologic toxicity in the dose-escalation part of the study;&#xD;
             if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled&#xD;
             must be evaluable for hematologic toxicity&#xD;
&#xD;
          -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) &gt;= 70&#xD;
             ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:&#xD;
&#xD;
               -  2 to &lt; 6 years: 0.8 mg/dL&#xD;
&#xD;
               -  6 to &lt; 10 years: 1 mg/dL&#xD;
&#xD;
               -  10 to &lt; 13 years: 1.2 mg/dL&#xD;
&#xD;
               -  13 to &lt; 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)&#xD;
&#xD;
               -  &gt;= 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)&#xD;
&#xD;
          -  Urine protein: =&lt; 30 mg/dl in urinalysis or =&lt; 1+ on dipstick, unless quantitative&#xD;
             protein is &lt; 1000 mg in a 24 hour (h) urine sample&#xD;
&#xD;
          -  Bilirubin (sum of conjugated + unconjugated) =&lt; 1.5 x upper limit of normal (ULN) for&#xD;
             age&#xD;
&#xD;
          -  Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =&lt; 110&#xD;
             U/L; for the purpose of this study, the ULN for SGPT is 45 U/L&#xD;
&#xD;
          -  Serum albumin &gt;= 2.8 g/dL&#xD;
&#xD;
          -  Prothrombin time (PT) and international normalized ratio (INR) =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Serum amylase =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Serum lipase =&lt; 1.5 x ULN&#xD;
&#xD;
          -  A blood pressure (BP) =&lt; the 95th percentile for age, height, and gender, and not&#xD;
             receiving medication for treatment of hypertension; please note that 3 serial blood&#xD;
             pressures should be obtained and averaged to determine baseline BP&#xD;
&#xD;
          -  Central nervous system function defined as: patients with seizure disorder may be&#xD;
             enrolled if receiving non-enzyme inducing anticonvulsants and well controlled&#xD;
&#xD;
          -  No history of congenital prolonged corrected QT interval (QTc) syndrome, New York&#xD;
             Heart Association (NYHA) class III or IV congestive heart failure (CHF)&#xD;
&#xD;
          -  No clinically significant cardiac arrhythmias, stroke or myocardial infarction within&#xD;
             6 months prior to enrollment&#xD;
&#xD;
          -  QTc =&lt; 480 msec; Note: patients with grade 1 prolonged QTc (450-480 msec) at the time&#xD;
             of study enrollment should have correctable causes of prolonged QTc addressed if&#xD;
             possible (i.e. electrolytes, medications)&#xD;
&#xD;
          -  All patients and/or their parents or legally authorized representatives must sign a&#xD;
             written informed consent; assent, when appropriate, will be obtained according to&#xD;
             institutional guidelines&#xD;
&#xD;
          -  Archival tumor tissue slides from either initial diagnosis or relapse must be sent; if&#xD;
             tumor tissue is unavailable, the study chair must be notified prior to enrollment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breast-feeding women will not be entered on this study; pregnancy tests&#xD;
             must be obtained in girls who are post-menarchal; males or females of reproductive&#xD;
             potential may not participate unless they have agreed to use two methods of birth&#xD;
             control - a medically accepted barrier method of contraceptive method (e.g., male or&#xD;
             female condom) and a second effective contraceptive method of birth control - during&#xD;
             protocol therapy and for at least 4 months after the last dose of XL184; abstinence is&#xD;
             an acceptable method of birth control&#xD;
&#xD;
          -  Patients receiving corticosteroids who have not been on a stable or decreasing dose of&#xD;
             corticosteroid for at least 7 days prior to enrollment are not eligible&#xD;
&#xD;
          -  Patients who are currently receiving another investigational drug are not eligible&#xD;
&#xD;
          -  Patients who are currently receiving other anti-cancer agents are not eligible&#xD;
&#xD;
          -  Patients who are receiving cyclosporine, tacrolimus or other agents to prevent&#xD;
             graft-versus-host disease post bone marrow transplant are not eligible for this trial&#xD;
&#xD;
          -  Patients must not be receiving any of the following potent cytochrome P450 family 3,&#xD;
             subfamily A, polypeptide 4 cytochrome (CYP3A4) inducers or inhibitors: erythromycin,&#xD;
             clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St.&#xD;
             John's wort&#xD;
&#xD;
          -  Patients who are receiving systemic treatment anticoagulation are not eligible;&#xD;
             patients receiving prophylactic systemic anticoagulation will be allowed as long as&#xD;
             eligibility PT/INR requirements are met&#xD;
&#xD;
          -  Patients must not have received enzyme-inducing anticonvulsants within 14 days prior&#xD;
             to enrollment&#xD;
&#xD;
          -  Patients who are receiving drugs that prolong QTc are not eligible&#xD;
&#xD;
          -  Patients must be able to swallow intact tablets; patients who cannot swallow intact&#xD;
             tablets are not eligible&#xD;
&#xD;
          -  Patients with active bleeding are not eligible; specifically, no clinically&#xD;
             significant gastrointestinal (GI) bleeding, GI perforation, intra-abdominal abscess or&#xD;
             fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary&#xD;
             hemorrhage for 3 months prior to enrollment&#xD;
&#xD;
          -  Patients with evidence of an acute intracranial or intratumoral hemorrhage on computed&#xD;
             tomography (CT) or magnetic resonance imaging (MRI) are not eligible (patients with&#xD;
             evidence of resolving hemorrhage will be eligible)&#xD;
&#xD;
          -  Patients who have had or are planning to have the following invasive procedures are&#xD;
             not eligible:&#xD;
&#xD;
               -  Major surgical procedure, laparoscopic procedure, open biopsy or significant&#xD;
                  traumatic injury within 28 days prior to enrollment&#xD;
&#xD;
               -  Central line placement or subcutaneous port placement is not considered major&#xD;
                  surgery but must be placed at least 3 days prior to enrollment for external lines&#xD;
                  (e.g. Hickman or Broviac) and at least 7 days prior to enrollment for&#xD;
                  subcutaneous port&#xD;
&#xD;
               -  Core biopsy within 7 days prior to enrollment&#xD;
&#xD;
               -  Fine needle aspirate within 7 days prior to enrollment&#xD;
&#xD;
               -  Surgical or other wounds must be adequately healed prior to enrollment&#xD;
&#xD;
          -  Patients on antihypertensive therapy for control of blood pressure at the time of&#xD;
             enrollment are not eligible&#xD;
&#xD;
          -  Patients with any medical or surgical conditions that would interfere with&#xD;
             gastrointestinal absorption of this oral agent are not eligible&#xD;
&#xD;
          -  Patients who have an uncontrolled infection are not eligible&#xD;
&#xD;
          -  Patients who have received a prior solid organ transplantation are not eligible&#xD;
&#xD;
          -  Patients who in the opinion of the investigator may not be able to comply with the&#xD;
             safety monitoring requirements of the study are not eligible&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Meredith K Chuk</last_name>
    <role>Principal Investigator</role>
    <affiliation>COG Phase I Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital of Alabama</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Orange County</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Center-Parnassus</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Center-Mission Bay</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's National Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>
  </location>
  <location>
    <facility>
      <name>Lurie Children's Hospital-Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riley Hospital for Children</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>C S Mott Children's Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota/Masonic Cancer Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </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>
  </location>
  <location>
    <facility>
      <name>Childrens Oncology Group</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Pittsburgh of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Children's Hospital</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <last_update_submitted>April 4, 2020</last_update_submitted>
  <last_update_submitted_qc>April 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Nervous System Neoplasms</mesh_term>
    <mesh_term>Central Nervous System Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Medullary</mesh_term>
    <mesh_term>Thyroid Neoplasms</mesh_term>
    <mesh_term>Thyroid Diseases</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <!-- 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/NCT01709435
org study id: NCI-2012-01890
secondary id: NCI-2012-01890
secondary id: P121149
secondary id: COG-ADVL1211
secondary id: NCI-2013-01571
secondary id: CDR0000741914
secondary id: ADVL1211
secondary id: ADVL1211
secondary id: UM1CA097452
nct id: NCT01709435
lead sponsor: 
has dmc: No
This phase I trial studies the side effects and best dose of cabozantinib S-malate in
      treating younger patients with solid tumors that have come back or no longer respond to
      treatment. Cabozantinib S-malate may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth.
PRIMARY OBJECTIVES:

      I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of XL184
      (cabozantinib) (cabozantinib S-malate) administered orally to children with refractory solid
      tumors including central nervous system (CNS) tumors.

      II. To define and describe the toxicities of XL184 (cabozantinib) administered on this
      schedule.

      III. To characterize the pharmacokinetics of XL184 (cabozantinib) in children with refractory
      solid tumors.

      SECONDARY OBJECTIVES:

      I. To preliminarily define the antitumor activity of XL184 (cabozantinib) within the confines
      of a phase 1 study.

      II. To assess the biologic activity of XL184 (cabozantinib). III. To assess the biomarker
      response (carcinoembryonic antigen [CEA] and calcitonin) in patients with medullary thyroid
      cancer treated with XL184.

      IV. To evaluate overall survival from study entry through a five-year follow-up period.

      OUTLINE: This is a dose-escalation study. (Complete as of 4/16/2014)

      Patients receive cabozantinib S-malate orally (PO) once daily (QD) on days 1-28. Courses
      repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days, 6 months, and then
      annually for up to 60 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD) and/or recommended phase 2 dose of cabozantinib S-malate
time frame: 28 days
description: Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. In addition to determination of the MTD, a descriptive summary of all toxicities will be reported.
measure: Pharmacokinetic (PK) parameters of cabozantinib S-malate including systemic exposure and drug clearance
time frame: Course 1, day 1 (pre-dose and 4 hours post dose), course 1 day 21 (+/- 2 days) (pre-dose, 2, 4, 8 and 24 hours post dose), course 3 day 1 (pre-dose)
description: Will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
measure: Disease response
time frame: Up to 5 years
description: Will be assessed according to Response Evaluation Criteria in Solid Tumors 1.1 criteria and reported descriptively.
measure: Overall survival (OS)
time frame: Up to 5 years
description: OS will also be assessed and summarized using the Kaplan-Meier method.
arm group label: Treatment (cabozantinib S-malate)
arm group type: Experimental
description: Patients receive cabozantinib S-malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Cabozantinib S-malate
description: Given PO
arm group label: Treatment (cabozantinib S-malate)
other name: BMS-907351
other name: Cabometyx
other name: Cometriq
other name: XL-184
other name: XL184
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (cabozantinib S-malate)
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Treatment (cabozantinib S-malate)
criteria: 
gender: All
minimum age: 2 Years
maximum age: 18 Years
healthy volunteers: No
last name: Meredith K Chuk
role: Principal Investigator
affiliation: COG Phase I Consortium
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Neoplasms
mesh term: Nervous System Neoplasms
mesh term: Central Nervous System Neoplasms
mesh term: Carcinoma, Medullary
mesh term: Thyroid Neoplasms
mesh term: Thyroid Diseases
mesh term: Recurrence