<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/NCT02202772</url>
  </required_header>
  <id_info>
    <org_study_id>AAAM8506</org_study_id>
    <nct_id>NCT02202772</nct_id>
  </id_info>
  <brief_title>Intravesical Cabazitaxel, Gemcitabine, and Cisplatin (CGC) in the Treatment Urothelial Carcinoma of the Bladder</brief_title>
  <acronym>CGC</acronym>
  <official_title>A Phase I Trial for the Use of Intravesical Cabazitaxel, Gemcitabine, and Cisplatin (CGC) in the Treatment of BCG-Refractory Non-muscle Invasive Urothelial Carcinoma of the Bladder Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>James M. McKiernan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators intend to evaluate the safety and toxicity proﬁle of intravesically&#xD;
      administered multidrug regimen of Cabazitaxel, Cisplatin and Gemcitabine in treatment&#xD;
      refractory Transitional Cell Carcinoma.The investigators propose to conduct a combined phase&#xD;
      I trial to assess the safety, toxicity, and efﬁcacy of a novel multidrug intravesical regimen&#xD;
      consisting of Cabazitaxel, Gemcitabine, and Cisplatin (CGC) in the treatment of BCG resistant&#xD;
      non-muscle invasive urothelial carcinoma of the bladder. This phase I trial will have a&#xD;
      combined dose and cycle-escalation scheme with enrollment of up to 24 patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nonsurgical treatment strategies for BCG refractory bladder cancer have failed to prove&#xD;
      themselves as reliable options for increased survival among this subset of bladder cancer&#xD;
      patients. For these patients, removal of the bladder with all the associated perioperative&#xD;
      risks and the subsequent reduction of quality of life, remains the only option. Prior&#xD;
      attempts at second line treatments have included intravesical (within the bladder)&#xD;
      monotherapy with a range of drugs including Gemcitabine and Paclitaxel (a taxane, similar to&#xD;
      Cabazitaxel). These drugs have shown some potential improvement for a small number of&#xD;
      patients Given the synergy of systemic chemotherapy, it is believed that a multidrug regimen&#xD;
      would allow for further improvement in survival among these patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 1, 2014</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1a/1b: The number of serious adverse events associated with therapy of intravesically administered Cabazitaxel, Gemcitabine, and Cisplatin.</measure>
    <time_frame>6 weeks from baseline</time_frame>
    <description>The investigator is measuring safety by looking at the number of events that occur during the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2: The number of complete responders after completion of six weeks of intravesically</measure>
    <time_frame>6 weeks from baseline</time_frame>
    <description>The investigator is measuring efficacy by the number of complete responders to the treatment</description>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">51</enrollment>
  <condition>Urothelial Carcinoma of the Urinary Bladder</condition>
  <arm_group>
    <arm_group_label>Gem and Low Cab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 2.5mg/100ml; 1 time a week for 6 weeks; 2 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gem and High Cab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gem, High Cab, and Low Cis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours Cisplatin: Intravesical; 66mg/100ml; 1 time a week for 6 weeks; 2 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gem, High Cab, Mod Cis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours Cisplatin: Intravesical; 80mg/100ml; 1 time a week for 6 weeks; 2 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gem, High Cab, High Cis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours Cisplatin: Intravesical; 100mg/100ml; 1 time a week for 6 weeks; 2 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabazitaxel</intervention_name>
    <description>Intravesical instillation of the Cabazitaxel for 2 hours</description>
    <arm_group_label>Gem and High Cab</arm_group_label>
    <arm_group_label>Gem and Low Cab</arm_group_label>
    <arm_group_label>Gem, High Cab, High Cis</arm_group_label>
    <arm_group_label>Gem, High Cab, Mod Cis</arm_group_label>
    <arm_group_label>Gem, High Cab, and Low Cis</arm_group_label>
    <other_name>Jevtana</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Intravesical instillation of Gemcitabine for 2 hours</description>
    <arm_group_label>Gem and High Cab</arm_group_label>
    <arm_group_label>Gem and Low Cab</arm_group_label>
    <arm_group_label>Gem, High Cab, High Cis</arm_group_label>
    <arm_group_label>Gem, High Cab, Mod Cis</arm_group_label>
    <arm_group_label>Gem, High Cab, and Low Cis</arm_group_label>
    <other_name>Gemzar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Intravesical installation of Cisplatin for 2hours</description>
    <arm_group_label>Gem, High Cab, High Cis</arm_group_label>
    <arm_group_label>Gem, High Cab, Mod Cis</arm_group_label>
    <arm_group_label>Gem, High Cab, and Low Cis</arm_group_label>
    <other_name>Platinol, Platinol-AQ</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients must have a histologically confirmed diagnosis of non- muscle invasive urothelial&#xD;
        carcinoma of the bladder at the study institution prior to the beginning of the study. This&#xD;
        includes patients with:&#xD;
&#xD;
          -  High grade Ta papillary lesion(s)&#xD;
&#xD;
          -  High or low grade T1 papillary lesion(s)&#xD;
&#xD;
          -  Carcinoma In Situ (CIS), with or without Ta or T1 papillary tumor(s) of any grade The&#xD;
             patient must have Bacillus Calmette-Guerin (BCG) refractory or recurrent non-muscle&#xD;
             invasive bladder cancer&#xD;
&#xD;
          -  Refractory disease is defined as evidence of persistent high risk bladder cancer (high&#xD;
             grade Ta, T1 and/or CIS) at the first cystoscopic exam after the initial 6 week&#xD;
             induction course of BCG or at the 6 month cystoscopic exam.&#xD;
&#xD;
          -  Recurrent disease is defined as reappearance of disease after achieving a tumor- free&#xD;
             status by 6 months following a full induction course of BCG with or without&#xD;
             maintenance BCG. Participants must have recurred within 18 months following the last&#xD;
             dose of BCG.&#xD;
&#xD;
               -  Low-grade superficial (Ta) disease will not be considered recurrent.&#xD;
&#xD;
               -  Patients must exhibit disease recurrence after receiving some form of standard&#xD;
                  intravesical therapy that must include a minimum of one induction course of BCG&#xD;
                  and may also include prior exposure to mitomycin, interferon, single agent&#xD;
                  gemcitabine or taxane therapy or maintenance.&#xD;
&#xD;
          -  Patients must be eligible for radical cystectomy and refuse this standard of care&#xD;
             treatment or not be a surgical candidate for radical cystectomy based on other&#xD;
             comorbidities.&#xD;
&#xD;
          -  All grossly visible disease in the bladder must be fully resected and pathologic stage&#xD;
             will be confirmed at the study institution.&#xD;
&#xD;
          -  Patients enrolled in other clinical trials must have received their last treatment at&#xD;
             least 6 weeks prior to enrollment.&#xD;
&#xD;
          -  Age &gt; 18 and must be able to read, understand and sign informed consent&#xD;
&#xD;
          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance Status:&#xD;
             ECOG of 0 or 1 including patients who are not surgical candidates due to comorbid&#xD;
             conditions.&#xD;
&#xD;
          -  Women of childbearing potential must have a negative pregnancy test.&#xD;
&#xD;
          -  All patients of childbearing potential must be willing to consent to using effective&#xD;
             contraception, i.e., intrauterine device (IUD), Birth control pills, Depo-Provera, and&#xD;
             condoms while on treatment and for 3 months after their participation in the study&#xD;
             ends.&#xD;
&#xD;
          -  No experimental intravesical therapy within 6 weeks of study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of severe hypersensitivity reaction (≥grade 3) to docetaxel&#xD;
&#xD;
          -  History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing&#xD;
             drugs&#xD;
&#xD;
          -  Concurrent or planned treatment with strong inhibitors or strong inducers of&#xD;
             cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are&#xD;
             already on I these treatments)&#xD;
&#xD;
          -  Concurrent malignancy diagnosed within 6 months of entry to the study.&#xD;
&#xD;
          -  Concurrent treatment with any systemic chemotherapeutic agent.&#xD;
&#xD;
          -  Inadequate organ and bone marrow function as evidenced by:&#xD;
&#xD;
               -  Hemoglobin: less than 8.0 g/dL&#xD;
&#xD;
               -  Absolute neutrophil count: less than 1.5 x 10^9/L&#xD;
&#xD;
               -  Platelet count: less than 80x 10^9/L&#xD;
&#xD;
               -  Aspartate Aminotransferase Test (AST) / Serum Glutamic Oxaloacetic Transaminase&#xD;
                  (SGOT) and/or ( Alanine Aminotransferase Test (ALT)/ Serum Glutamic Pyruvic&#xD;
                  Transaminase (SGPT) &gt;2.5 x upper limit of normal (ULN);&#xD;
&#xD;
               -  Total bilirubin &gt;1.5 x ULN&#xD;
&#xD;
               -  Serum creatinine &gt;2 x ULN. If creatinine 1.5 - 2.0 x ULN, creatinine clearance&#xD;
                  will be calculated according to Chronic Kidney Disease Epidemiology Collaboration&#xD;
                  (CKD-EPI) formula and patients with creatinine clearance &lt;30 mL/min should be&#xD;
                  excluded.&#xD;
&#xD;
          -  Women who are pregnant or lactating.&#xD;
&#xD;
          -  Documented history of vesicoureteral reflux or an indwelling urinary stent.&#xD;
&#xD;
          -  Participation in any other research protocol involving administration of an&#xD;
             investigational agent within 6 weeks prior to study entry.&#xD;
&#xD;
          -  No Institutional Review Board (IRB) approved signed consent form&#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>Guarionex DeCastro, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Research Nurse Navigator</last_name>
    <phone>(212) 342-5162</phone>
    <email>cancerclinicaltrials@cumc.columbia.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Columbia University Medical Center- HIP</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Guarionex Decastro, MD</last_name>
      <phone>212-305-0114</phone>
      <email>gjd16@cumc.columbia.edu</email>
    </contact>
    <investigator>
      <last_name>James McKiernan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Guarionex Decastro, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Christopher Anderson, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://cancer.columbia.edu/</url>
    <description>Columbia University current clinical trials</description>
  </link>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>July 25, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <last_update_submitted>February 3, 2022</last_update_submitted>
  <last_update_submitted_qc>February 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>James M. McKiernan</investigator_full_name>
    <investigator_title>Chairman of Urology</investigator_title>
  </responsible_party>
  <keyword>Urothelial</keyword>
  <keyword>Cisplatin</keyword>
  <keyword>Gemcitabine</keyword>
  <keyword>Cabazitaxel</keyword>
  <keyword>Bladder</keyword>
  <keyword>Carcinoma</keyword>
  <keyword>Bacillus Calmette-Guerin</keyword>
  <keyword>Intravesical</keyword>
  <keyword>Recurrent</keyword>
  <keyword>Non-muscle</keyword>
  <keyword>Invasive</keyword>
  <keyword>Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Transitional Cell</mesh_term>
    <mesh_term>Urinary Bladder Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02202772
org study id: AAAM8506
nct id: NCT02202772
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The investigators intend to evaluate the safety and toxicity proﬁle of intravesically
      administered multidrug regimen of Cabazitaxel, Cisplatin and Gemcitabine in treatment
      refractory Transitional Cell Carcinoma.The investigators propose to conduct a combined phase
      I trial to assess the safety, toxicity, and efﬁcacy of a novel multidrug intravesical regimen
      consisting of Cabazitaxel, Gemcitabine, and Cisplatin (CGC) in the treatment of BCG resistant
      non-muscle invasive urothelial carcinoma of the bladder. This phase I trial will have a
      combined dose and cycle-escalation scheme with enrollment of up to 24 patients.
Nonsurgical treatment strategies for BCG refractory bladder cancer have failed to prove
      themselves as reliable options for increased survival among this subset of bladder cancer
      patients. For these patients, removal of the bladder with all the associated perioperative
      risks and the subsequent reduction of quality of life, remains the only option. Prior
      attempts at second line treatments have included intravesical (within the bladder)
      monotherapy with a range of drugs including Gemcitabine and Paclitaxel (a taxane, similar to
      Cabazitaxel). These drugs have shown some potential improvement for a small number of
      patients Given the synergy of systemic chemotherapy, it is believed that a multidrug regimen
      would allow for further improvement in survival among these patients.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1a/1b: The number of serious adverse events associated with therapy of intravesically administered Cabazitaxel, Gemcitabine, and Cisplatin.
time frame: 6 weeks from baseline
description: The investigator is measuring safety by looking at the number of events that occur during the study
measure: Phase 2: The number of complete responders after completion of six weeks of intravesically
time frame: 6 weeks from baseline
description: The investigator is measuring efficacy by the number of complete responders to the treatment
arm group label: Gem and Low Cab
arm group type: Experimental
description: Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 2.5mg/100ml; 1 time a week for 6 weeks; 2 hours
arm group label: Gem and High Cab
arm group type: Experimental
description: Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours
arm group label: Gem, High Cab, and Low Cis
arm group type: Experimental
description: Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours Cisplatin: Intravesical; 66mg/100ml; 1 time a week for 6 weeks; 2 hours
arm group label: Gem, High Cab, Mod Cis
arm group type: Experimental
description: Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours Cisplatin: Intravesical; 80mg/100ml; 1 time a week for 6 weeks; 2 hours
arm group label: Gem, High Cab, High Cis
arm group type: Experimental
description: Gemcitabine: Intravesical; 2000mg/100ml; 1 time a week for 6 weeks; 2 hours Cabazitaxel: Intravesical; 5mg/100ml; 1 time a week for 6 weeks; 2 hours Cisplatin: Intravesical; 100mg/100ml; 1 time a week for 6 weeks; 2 hours
intervention type: Drug
intervention name: Cabazitaxel
description: Intravesical instillation of the Cabazitaxel for 2 hours
arm group label: Gem and High Cab
arm group label: Gem and Low Cab
arm group label: Gem, High Cab, High Cis
arm group label: Gem, High Cab, Mod Cis
arm group label: Gem, High Cab, and Low Cis
other name: Jevtana
intervention type: Drug
intervention name: Gemcitabine
description: Intravesical instillation of Gemcitabine for 2 hours
arm group label: Gem and High Cab
arm group label: Gem and Low Cab
arm group label: Gem, High Cab, High Cis
arm group label: Gem, High Cab, Mod Cis
arm group label: Gem, High Cab, and Low Cis
other name: Gemzar
intervention type: Drug
intervention name: Cisplatin
description: Intravesical installation of Cisplatin for 2hours
arm group label: Gem, High Cab, High Cis
arm group label: Gem, High Cab, Mod Cis
arm group label: Gem, High Cab, and Low Cis
other name: Platinol, Platinol-AQ
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Guarionex DeCastro, MD
role: Principal Investigator
affiliation: Columbia University
last name: Research Nurse Navigator
phone: (212) 342-5162
email: cancerclinicaltrials@cumc.columbia.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
country: United States
url: https://cancer.columbia.edu/
description: Columbia University current clinical trials
responsible party type: Sponsor-Investigator
investigator affiliation: Columbia University
investigator full name: James M. McKiernan
investigator title: Chairman of Urology
mesh term: Carcinoma
mesh term: Carcinoma, Transitional Cell
mesh term: Urinary Bladder Neoplasms
mesh term: Cisplatin
mesh term: Gemcitabine
sharing ipd: Undecided