<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/NCT01663285</url>
  </required_header>
  <id_info>
    <org_study_id>UMCC 2012.038</org_study_id>
    <secondary_id>HUM00062285</secondary_id>
    <nct_id>NCT01663285</nct_id>
  </id_info>
  <brief_title>Clinical Trial Of Neoadjuvant Chemotherapy (NAC)In Upper Tract Urothelial Carcinoma (UTUC)</brief_title>
  <official_title>Phase II Clinical Trial Of Neoadjuvant Chemotherapy (NAC)In Upper Tract Urothelial Carcinoma (UTUC)</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>
      The main purpose of this study is to look at the cancer-free survival at two years of&#xD;
      subjects with high risk upper tract urothelial cancer when treated with the combination of&#xD;
      two chemotherapy drugs called Gemcitabine and Cisplatin followed by surgery to remove the&#xD;
      kidney, all or part of the ureter (ureters are tubes made of smooth muscle fibers that propel&#xD;
      urine from the kidneys to the urinary bladder), and a cuff of bladder where the ureter drains&#xD;
      into the bladder. Other purposes of the study include looking at the safety of Gemcitabine&#xD;
      and Cisplatin before surgery for this type of cancer, time to recurrence of cancer, and&#xD;
      overall survival.&#xD;
&#xD;
      Exploratory integrative tumor sequencing:&#xD;
&#xD;
      The purpose of this part of the study is to test deoxyribonucleic acid (DNA) and ribonucleic&#xD;
      acid (RNA) in various types of samples (tissue and blood) to detect different types of cancer&#xD;
      genetic changes in upper tract urothelial cancer (UTUC) to help develop future studies in&#xD;
      UTUC. DNA and RNA contain key instructions for cell function and help determine the&#xD;
      characteristics of each individual such as hair, eye, and skin color, height, susceptibility&#xD;
      to diseases, and other characteristics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In recent years, the combination of gemcitabine and cisplatin given every 21 days&#xD;
      (gemcitabine on days 1 and 8 only) has been used in trials and routine clinical practice.&#xD;
      Additionally, surgery, primarily radical nephroureterectomy (RNU) with bladder cuff removal,&#xD;
      is the current standard treatment for invasive upper tract urothelial carcinoma.&#xD;
&#xD;
      Upper tract urothelial cancer (UTUC) or urothelial cancer arising in the pelvicalyceal or&#xD;
      ureteral locations is a lethal cancer accounting for 5% of all urothelial cancers. In&#xD;
      urothelial cancer of the bladder, randomized clinical trials and meta-analyses have shown a&#xD;
      survival advantage with neoadjuvant cisplatin-based chemotherapy. It is conceivable that a&#xD;
      similar approach may benefit patients with UTUC.&#xD;
&#xD;
      Both Gemcitabine and Cisplatin are approved by the FDA. Cisplatin is approved for use in&#xD;
      urothelial cancer. Gemcitabine is FDA approved to be used alone or with other drugs to treat&#xD;
      breast, non-small lung, ovarian, and pancreatic cancers. Gemcitabine is not approved by the&#xD;
      FDA for urothelial cancer, but it is typically used together with Cisplatin in trials and&#xD;
      routine clinical practice for treating urothelial cancer.&#xD;
&#xD;
      Exploratory integrative tumor sequencing:&#xD;
&#xD;
      The biology of UTUC is poorly understood due to the relative rarity of the disease and the&#xD;
      lack of comprehensive genomic and translational studies. This trial offers a rare opportunity&#xD;
      to apply high-throughput sequencing techniques in UTUC to detect several classes of cancer&#xD;
      mutations including structural rearrangements, copy number alterations, point mutations, and&#xD;
      gene expression alterations. This research could help to develop future studies in UTUC to&#xD;
      help researchers understand more about UTUC and how to treat it. Additionally, we may&#xD;
      identify a potentially important result from DNA samples from subjects that could possibly&#xD;
      help manage their cancer better by pursing a different cancer therapy rather than the study&#xD;
      therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low study participant enrollment.&#xD;
  </why_stopped>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">January 2014</completion_date>
  <primary_completion_date type="Actual">January 2014</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>Recurrence-free Survival Time</measure>
    <time_frame>2 years after participant surgery</time_frame>
    <description>The 2-year recurrence-free survival (RFS) time for patients treated with neoadjuvant cisplatin and gemcitabine chemotherapy followed by surgery in high risk upper tract urothelial carcinoma.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Pathologic T0/Tis/Ta N0.</measure>
    <time_frame>51 months</time_frame>
    <description>The proportion of patients with pathologic T0/Tis/Ta N0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>9 years</time_frame>
    <description>The safety of neoadjuvant chemotherapy.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Urothelial Cancer</condition>
  <condition>Bladder Cancer</condition>
  <arm_group>
    <arm_group_label>Neoadjuvant Gemcitabine and Cisplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Neoadjuvant Cisplatin and Gemcitabine</intervention_name>
    <description>Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.</description>
    <arm_group_label>Neoadjuvant Gemcitabine and Cisplatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have HIGH GRADE upper tract urothelial carcinoma&#xD;
&#xD;
          -  Patients must be considered to be a candidate for surgery with curative intent&#xD;
             (nephroureterectomy or distal ureterectomy) with lymph node dissection by the treating&#xD;
             urologist at baseline within 42 days prior to registration.&#xD;
&#xD;
          -  Patients must be able to care for themselves and must be up and about more than 50% of&#xD;
             waking hours&#xD;
&#xD;
          -  All patients must be evaluated by a medical oncologist at baseline within 42 days&#xD;
             prior to registration. Patients must be considered to be a candidate for&#xD;
             cisplatin-based neoadjuvant chemotherapy by a medical oncologist at baseline and must&#xD;
             have adequate kidney function and any pre-existing peripheral neuropathy must be&#xD;
             moderate to mild.&#xD;
&#xD;
          -  Prior uro-oncologic history:&#xD;
&#xD;
               -  History of or active non-invasive carcinoma or carcinoma in situ of the bladder&#xD;
                  or upper tract is allowed.&#xD;
&#xD;
               -  Patients may have received prior intravesical chemotherapy or immunotherapy such&#xD;
                  as BCG.&#xD;
&#xD;
               -  Prior neoadjuvant chemotherapy for bladder cancer or invasive contralateral upper&#xD;
                  tract cancer is allowed.&#xD;
&#xD;
               -  Prior adjuvant chemotherapy for bladder cancer or invasive contralateral upper&#xD;
                  tract cancer is allowed but must have been completed ≥2 years prior to study&#xD;
                  registration.&#xD;
&#xD;
          -  Patients must have adequate organ and bone marrow function as determined by screening&#xD;
             tests&#xD;
&#xD;
          -  Patients must have recovered from any reversible toxicities of prior procedure or&#xD;
             surgery&#xD;
&#xD;
          -  Patients must be 18 years or older on date of registration&#xD;
&#xD;
          -  All patients must be informed of the investigational nature of this study and must&#xD;
             sign an informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients must have no evidence of regional lymphadenopathy or distant metastasis on&#xD;
             imaging.&#xD;
&#xD;
          -  No history of invasive or node positive or metastatic bladder cancer or invasive&#xD;
             contralateral upper tract cancer within 2 years prior to registration.&#xD;
&#xD;
          -  Patients with one kidney are not eligible&#xD;
&#xD;
          -  Patients may not be enrolled in another interventional clinical trial at the time of&#xD;
             registration.&#xD;
&#xD;
          -  No prior non-urothelial malignancy is allowed, except for cancer from which the&#xD;
             patient has been disease free for at least 1 year at the discretion of the treating&#xD;
             oncologist. History of adequately treated (at the discretion of the treating&#xD;
             oncologist) basal cell or squamous cell skin cancer or in situ cervical cancers is&#xD;
             allowed.&#xD;
&#xD;
          -  Pregnant or lactating women are not eligible. Women/men of reproductive potential must&#xD;
             agree to use an effective contraceptive method. Women with reproductive potential must&#xD;
             have a negative pregnancy test within 14 days prior to registration.&#xD;
&#xD;
          -  Patients must not have any other medical condition(s) that make(s) their participation&#xD;
             in the study unadvisable in the opinion of the treating oncologist.&#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>Ajjai S. Alva, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health Sciences University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2015</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>September 11, 2014</results_first_submitted>
  <results_first_submitted_qc>September 11, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">September 18, 2014</results_first_posted>
  <last_update_submitted>November 4, 2015</last_update_submitted>
  <last_update_submitted_qc>November 4, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Urothelial</keyword>
  <keyword>Bladder</keyword>
  <keyword>Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Transitional Cell</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>Neoadjuvant Gemcitabine and Cisplatin</title>
          <description>Neoadjuvant Cisplatin and Gemcitabine: Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Neoadjuvant Gemcitabine and Cisplatin</title>
          <description>Neoadjuvant Cisplatin and Gemcitabine: Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46" lower_limit="46" upper_limit="46"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Recurrence-free Survival Time</title>
        <description>The 2-year recurrence-free survival (RFS) time for patients treated with neoadjuvant cisplatin and gemcitabine chemotherapy followed by surgery in high risk upper tract urothelial carcinoma.</description>
        <time_frame>2 years after participant surgery</time_frame>
        <population>Due to poor patient enrollment the primary objective was not able to be analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Gemcitabine and Cisplatin</title>
            <description>Neoadjuvant Cisplatin and Gemcitabine: Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Recurrence-free Survival Time</title>
          <description>The 2-year recurrence-free survival (RFS) time for patients treated with neoadjuvant cisplatin and gemcitabine chemotherapy followed by surgery in high risk upper tract urothelial carcinoma.</description>
          <population>Due to poor patient enrollment the primary objective was not able to be analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Pathologic T0/Tis/Ta N0.</title>
        <description>The proportion of patients with pathologic T0/Tis/Ta N0.</description>
        <time_frame>51 months</time_frame>
        <population>Due to poor patient enrollment this outcome was not able to be analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Gemcitabine and Cisplatin</title>
            <description>Neoadjuvant Cisplatin and Gemcitabine: Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Pathologic T0/Tis/Ta N0.</title>
          <description>The proportion of patients with pathologic T0/Tis/Ta N0.</description>
          <population>Due to poor patient enrollment this outcome was not able to be analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>The safety of neoadjuvant chemotherapy.</description>
        <time_frame>9 years</time_frame>
        <population>Due to poor patient enrollment this outcome was not able to be analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Neoadjuvant Gemcitabine and Cisplatin</title>
            <description>Neoadjuvant Cisplatin and Gemcitabine: Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>The safety of neoadjuvant chemotherapy.</description>
          <population>Due to poor patient enrollment this outcome was not able to be analyzed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Neoadjuvant Gemcitabine and Cisplatin</title>
          <description>Neoadjuvant Cisplatin and Gemcitabine: Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Creatinine Increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="0" subjects_at_risk="1"/>
              </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 study was terminated prematurely due to poor patient accrual. Study objectives were not analyzed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Ajjai Alva</name_or_title>
      <organization>University of Michigan Comprehensive Cancer Center</organization>
      <phone>734-647-8921</phone>
      <email>ajjai@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/NCT01663285
org study id: UMCC 2012.038
secondary id: HUM00062285
nct id: NCT01663285
lead sponsor: 
has dmc: Yes
The main purpose of this study is to look at the cancer-free survival at two years of
      subjects with high risk upper tract urothelial cancer when treated with the combination of
      two chemotherapy drugs called Gemcitabine and Cisplatin followed by surgery to remove the
      kidney, all or part of the ureter (ureters are tubes made of smooth muscle fibers that propel
      urine from the kidneys to the urinary bladder), and a cuff of bladder where the ureter drains
      into the bladder. Other purposes of the study include looking at the safety of Gemcitabine
      and Cisplatin before surgery for this type of cancer, time to recurrence of cancer, and
      overall survival.

      Exploratory integrative tumor sequencing:

      The purpose of this part of the study is to test deoxyribonucleic acid (DNA) and ribonucleic
      acid (RNA) in various types of samples (tissue and blood) to detect different types of cancer
      genetic changes in upper tract urothelial cancer (UTUC) to help develop future studies in
      UTUC. DNA and RNA contain key instructions for cell function and help determine the
      characteristics of each individual such as hair, eye, and skin color, height, susceptibility
      to diseases, and other characteristics.
In recent years, the combination of gemcitabine and cisplatin given every 21 days
      (gemcitabine on days 1 and 8 only) has been used in trials and routine clinical practice.
      Additionally, surgery, primarily radical nephroureterectomy (RNU) with bladder cuff removal,
      is the current standard treatment for invasive upper tract urothelial carcinoma.

      Upper tract urothelial cancer (UTUC) or urothelial cancer arising in the pelvicalyceal or
      ureteral locations is a lethal cancer accounting for 5% of all urothelial cancers. In
      urothelial cancer of the bladder, randomized clinical trials and meta-analyses have shown a
      survival advantage with neoadjuvant cisplatin-based chemotherapy. It is conceivable that a
      similar approach may benefit patients with UTUC.

      Both Gemcitabine and Cisplatin are approved by the FDA. Cisplatin is approved for use in
      urothelial cancer. Gemcitabine is FDA approved to be used alone or with other drugs to treat
      breast, non-small lung, ovarian, and pancreatic cancers. Gemcitabine is not approved by the
      FDA for urothelial cancer, but it is typically used together with Cisplatin in trials and
      routine clinical practice for treating urothelial cancer.

      Exploratory integrative tumor sequencing:

      The biology of UTUC is poorly understood due to the relative rarity of the disease and the
      lack of comprehensive genomic and translational studies. This trial offers a rare opportunity
      to apply high-throughput sequencing techniques in UTUC to detect several classes of cancer
      mutations including structural rearrangements, copy number alterations, point mutations, and
      gene expression alterations. This research could help to develop future studies in UTUC to
      help researchers understand more about UTUC and how to treat it. Additionally, we may
      identify a potentially important result from DNA samples from subjects that could possibly
      help manage their cancer better by pursing a different cancer therapy rather than the study
      therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recurrence-free Survival Time
time frame: 2 years after participant surgery
description: The 2-year recurrence-free survival (RFS) time for patients treated with neoadjuvant cisplatin and gemcitabine chemotherapy followed by surgery in high risk upper tract urothelial carcinoma.
measure: Number of Patients With Pathologic T0/Tis/Ta N0.
time frame: 51 months
description: The proportion of patients with pathologic T0/Tis/Ta N0.
measure: Number of Participants With Adverse Events
time frame: 9 years
description: The safety of neoadjuvant chemotherapy.
arm group label: Neoadjuvant Gemcitabine and Cisplatin
arm group type: Experimental
description: Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.
intervention type: Drug
intervention name: Neoadjuvant Cisplatin and Gemcitabine
description: Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.
arm group label: Neoadjuvant Gemcitabine and Cisplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ajjai S. Alva, M.D.
role: Principal Investigator
affiliation: University of Michigan
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Transitional Cell
mesh term: Gemcitabine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was terminated prematurely due to poor patient accrual. Study objectives were not analyzed.
point of contact: 