<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/NCT01663272</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2011.105</org_study_id>
    <secondary_id>HUM 62927</secondary_id>
    <nct_id>NCT01663272</nct_id>
  </id_info>
  <brief_title>A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer</brief_title>
  <official_title>A Trial of Cabozantinib (XL184) and Gemcitabine in Advanced Pancreatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan Rogel Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan Rogel Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Gemcitabine is considered one of the standard drugs for advanced pancreatic cancer and is&#xD;
      approved by the FDA to treat it. Cabozantinib is a new drug that has demonstrated&#xD;
      effectiveness against pancreatic cancer in laboratory experiments, especially when given with&#xD;
      gemcitabine. Initial studies with cabozantinib in pancreatic cancer have shown some activity&#xD;
      against the disease. The purpose of this study is to determine the safest and highest dose of&#xD;
      cabozantinib that can be given together with standard doses of gemcitabine in patients with&#xD;
      pancreatic cancer. This study will determine the safety and tolerability of this two drug&#xD;
      combination.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preclinical work at the University of Michigan has demonstrated that inhibition of c-Met with&#xD;
      cabozantinib prevented the development of metastatic disease in an intra-cardiac injection&#xD;
      model in NOD/SCID mice. Additionally, the combination of cabozantinib and gemcitabine&#xD;
      demonstrated improved tumor control compared to either agent alone in a relevant orthotopic&#xD;
      implantation mouse model.&#xD;
&#xD;
      Combining gemcitabine with the c-Met inhibitor cabozantinib in advanced pancreatic cancer is&#xD;
      a novel strategy that takes advantage of an established cytotoxic agent with one that targets&#xD;
      a pathway known to be important for the growth, dissemination, and resistance of this&#xD;
      disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">March 1, 2017</completion_date>
  <primary_completion_date type="Actual">January 2015</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</measure>
    <time_frame>5 weeks</time_frame>
    <description>The MTD is defined at the highest dose level at which ≤25% of patients experience a dose-limiting toxicity (DLT).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Progression-free Survival (PFS)</measure>
    <time_frame>day-7 of cycle 1 until 30 days post treatment</time_frame>
    <description>Progression-free survival (PFS, a secondary endpoint) will be calculated from day-7 of cycle 1 of study treatment, until documented disease progression or death. Patients removed from treatment for progression or other reasons will be followed for 30 days after their last dose.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>cabozantinib with gemcitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The Study Treatment Period will consist of continued treatment during which time patients will receive cabozantinib and gemcitabine until either disease progression or the occurrence of unacceptable drug-related toxicity</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CABOZANTINIB</intervention_name>
    <description>Daily oral cabozantinib administered days -7 until disease progression, intolerable adverse event(s) or patient choice.</description>
    <arm_group_label>cabozantinib with gemcitabine</arm_group_label>
    <other_name>XL184</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>gemcitabine</intervention_name>
    <description>Gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.</description>
    <arm_group_label>cabozantinib with gemcitabine</arm_group_label>
    <other_name>Gemzar</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. pathologically confirmed pancreatic carcinoma.&#xD;
&#xD;
          2. locally advanced unresectable disease, metastatic disease, or recurrent disease&#xD;
             following surgical therapy.&#xD;
&#xD;
          3. ≥ 18 years old.&#xD;
&#xD;
          4. Life expectancy of greater than 12 weeks.&#xD;
&#xD;
          5. ECOG performance status ≤1 (Karnofsky ≥70%) (See Appendix A).&#xD;
&#xD;
          6. adequate organ and marrow function as follows:&#xD;
&#xD;
          7. capable of understanding and complying with the protocol requirements and has signed&#xD;
             the informed consent document.&#xD;
&#xD;
          8. use medically accepted barrier methods of contraception&#xD;
&#xD;
          9. women of childbearing potential must have a negative pregnancy test at screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. neuroendocrine tumors of the pancreas.&#xD;
&#xD;
          2. more than 1 prior systemic treatment regimen for pancreatic cancer. may have received&#xD;
             prior neoadjuvant or adjuvant therapy, including gemcitabine, provided 6 months have&#xD;
             elapsed from completion of that treatment and the start of study therapy.&#xD;
&#xD;
          3. Previous gemcitabine therapy for advanced pancreatic cancer. Patients who have had&#xD;
             chemotherapy within 4 weeks, nitrosoureas/mitomycin C within 6 weeks, or monoclonal&#xD;
             antibody within 6 weeks prior to planned initiation of study treatment.&#xD;
&#xD;
          4. prior treatment with a small molecule kinase inhibitor or a hormonal therapy within 14&#xD;
             days or five half-lives of the compound or active metabolites, whichever is longer,&#xD;
             before the first dose of study treatment.&#xD;
&#xD;
          5. have received an investigational agent within 28 days of the first dose of study&#xD;
             treatment or 5 half-lives of the compound or active metabolite, whichever is longer.&#xD;
&#xD;
          6. have received radiation therapy within 14 days of study treatment.&#xD;
&#xD;
          7. have not recovered from toxicity due to all prior therapies (i.e., return to&#xD;
             pretherapy baseline or to CTCAE Grade 0 or 1) except alopecia and non-clinically&#xD;
             significant AEs.&#xD;
&#xD;
          8. known brain metastases.&#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>Mark Zalupski, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan Rogel Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Zhen DB, Griffith KA, Ruch JM, Camphausen K, Savage JE, Kim EJ, Sahai V, Simeone DM, Zalupski MM. A phase I trial of cabozantinib and gemcitabine in advanced pancreatic cancer. Invest New Drugs. 2016 Dec;34(6):733-739. doi: 10.1007/s10637-016-0376-1. Epub 2016 Jul 21.</citation>
    <PMID>27439894</PMID>
  </results_reference>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>July 24, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <results_first_submitted>May 18, 2017</results_first_submitted>
  <results_first_submitted_qc>September 18, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">September 19, 2018</results_first_posted>
  <last_update_submitted>September 18, 2018</last_update_submitted>
  <last_update_submitted_qc>September 18, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>oncology</keyword>
  <keyword>pancrease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Dose Level -1</title>
          <description>20 mg of cabozantinib PO daily administered days -7 until disease progression, intolerable adverse event(s) or patient choice.&#xD;
800mg/m^2 of gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.</description>
        </group>
        <group group_id="P2">
          <title>Dose Level 1</title>
          <description>20 mg of cabozantinib PO daily administered days -7 until disease progression, intolerable adverse event(s) or patient choice.&#xD;
1000mg/m^2 of gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.</description>
        </group>
        <group group_id="P3">
          <title>Dose Level 2</title>
          <description>40 mg of cabozantinib PO daily administered days -7 until disease progression, intolerable adverse event(s) or patient choice.&#xD;
1000mg/m^2 of gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cabozantinib With Gemcitabine</title>
          <description>Patients received daily oral cabozantinib, at 20mg or 40mg, administered days -7 until disease progression, intolerable adverse event(s) or patient choice AND Gemcitabine at 800mg/m^2 or 1000mg/m^2 administered intravenously on days 1, 8, and 15 every 28 days.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.5" lower_limit="41" upper_limit="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Tolerated Dose</title>
        <description>The MTD is defined at the highest dose level at which ≤25% of patients experience a dose-limiting toxicity (DLT).</description>
        <time_frame>5 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cabozantinib With Gemcitabine</title>
            <description>The Study Treatment Period will consist of continued treatment during which time patients will receive cabozantinib and gemcitabine until either disease progression or the occurrence of unacceptable drug-related toxicity&#xD;
Cabozantinib: Daily oral cabozantinib (20mg OR 40mg) administered days -7 until disease progression, intolerable adverse event(s) or patient choice.&#xD;
Gemcitabine: Gemcitabine (800mg/m^2 OR 1000mg/m^2) administered intravenously on days 1, 8, and 15 every 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Tolerated Dose</title>
          <description>The MTD is defined at the highest dose level at which ≤25% of patients experience a dose-limiting toxicity (DLT).</description>
          <units>mg</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">The MTD could not be determined as too many patients experienced toxicity at all dose levels.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Progression-free Survival (PFS)</title>
        <description>Progression-free survival (PFS, a secondary endpoint) will be calculated from day-7 of cycle 1 of study treatment, until documented disease progression or death. Patients removed from treatment for progression or other reasons will be followed for 30 days after their last dose.</description>
        <time_frame>day-7 of cycle 1 until 30 days post treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Cabozantinib With Gemcitabine</title>
            <description>The Study Treatment Period will consist of continued treatment during which time patients will receive cabozantinib and gemcitabine until either disease progression or the occurrence of unacceptable drug-related toxicity&#xD;
Cabozantinib: Daily oral cabozantinib (20mg OR 40mg) administered days -7 until disease progression, intolerable adverse event(s) or patient choice.&#xD;
Gemcitabine: Gemcitabine (800mg/m^2 OR 1000mg/m^2) administered intravenously on days 1, 8, and 15 every 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Progression-free Survival (PFS)</title>
          <description>Progression-free survival (PFS, a secondary endpoint) will be calculated from day-7 of cycle 1 of study treatment, until documented disease progression or death. Patients removed from treatment for progression or other reasons will be followed for 30 days after their last dose.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" lower_limit="1.4" upper_limit="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Cabozantinib With Gemcitabine</title>
          <description>Adverse events were pooled for all treated patients and were not collected by dose level. Patients received daily oral cabozantinib, at 20mg or 40mg, administered days -7 until disease progression, intolerable adverse event(s) or patient choice AND Gemcitabine at 800mg/m^2 or 1000mg/m^2 administered intravenously on days 1, 8, and 15 every 28 days.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal Fistula</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Bile Duct Stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death, NOS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Flu Like Symptoms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="5" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Anal hemorrhage</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rectal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="11" subjects_affected="8" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Biliary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Papulopustular rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="28" subjects_affected="11" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="11" subjects_affected="7" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="16" subjects_affected="9" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="21" subjects_affected="9" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="24" subjects_affected="10" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="31" subjects_affected="10" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="10" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="4" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The MTD could not be determined as too many patients experienced toxicity.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Mark Zalupski, M.D.</name_or_title>
      <organization>University of Michigan Comprehensive Cancer Center</organization>
      <phone>734-647-8902</phone>
      <email>zalupski@med.umich.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01663272
org study id: UMCC 2011.105
secondary id: HUM 62927
nct id: NCT01663272
lead sponsor: 
has dmc: Yes
Gemcitabine is considered one of the standard drugs for advanced pancreatic cancer and is
      approved by the FDA to treat it. Cabozantinib is a new drug that has demonstrated
      effectiveness against pancreatic cancer in laboratory experiments, especially when given with
      gemcitabine. Initial studies with cabozantinib in pancreatic cancer have shown some activity
      against the disease. The purpose of this study is to determine the safest and highest dose of
      cabozantinib that can be given together with standard doses of gemcitabine in patients with
      pancreatic cancer. This study will determine the safety and tolerability of this two drug
      combination.
Preclinical work at the University of Michigan has demonstrated that inhibition of c-Met with
      cabozantinib prevented the development of metastatic disease in an intra-cardiac injection
      model in NOD/SCID mice. Additionally, the combination of cabozantinib and gemcitabine
      demonstrated improved tumor control compared to either agent alone in a relevant orthotopic
      implantation mouse model.

      Combining gemcitabine with the c-Met inhibitor cabozantinib in advanced pancreatic cancer is
      a novel strategy that takes advantage of an established cytotoxic agent with one that targets
      a pathway known to be important for the growth, dissemination, and resistance of this
      disease.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose
time frame: 5 weeks
description: The MTD is defined at the highest dose level at which ≤25% of patients experience a dose-limiting toxicity (DLT).
measure: Median Progression-free Survival (PFS)
time frame: day-7 of cycle 1 until 30 days post treatment
description: Progression-free survival (PFS, a secondary endpoint) will be calculated from day-7 of cycle 1 of study treatment, until documented disease progression or death. Patients removed from treatment for progression or other reasons will be followed for 30 days after their last dose.
arm group label: cabozantinib with gemcitabine
arm group type: Experimental
description: The Study Treatment Period will consist of continued treatment during which time patients will receive cabozantinib and gemcitabine until either disease progression or the occurrence of unacceptable drug-related toxicity
intervention type: Drug
intervention name: CABOZANTINIB
description: Daily oral cabozantinib administered days -7 until disease progression, intolerable adverse event(s) or patient choice.
arm group label: cabozantinib with gemcitabine
other name: XL184
intervention type: Drug
intervention name: gemcitabine
description: Gemcitabine administered intravenously on days 1, 8, and 15 every 28 days.
arm group label: cabozantinib with gemcitabine
other name: Gemzar
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mark Zalupski, MD
role: Principal Investigator
affiliation: University of Michigan Rogel Cancer Center
facility: 
country: United States
citation: Zhen DB, Griffith KA, Ruch JM, Camphausen K, Savage JE, Kim EJ, Sahai V, Simeone DM, Zalupski MM. A phase I trial of cabozantinib and gemcitabine in advanced pancreatic cancer. Invest New Drugs. 2016 Dec;34(6):733-739. doi: 10.1007/s10637-016-0376-1. Epub 2016 Jul 21.
PMID: 27439894
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
mesh term: Gemcitabine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The MTD could not be determined as too many patients experienced toxicity.
point of contact: 