<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/NCT03296306</url>
  </required_header>
  <id_info>
    <org_study_id>KCSG GU16-02</org_study_id>
    <nct_id>NCT03296306</nct_id>
  </id_info>
  <brief_title>Four Cycles Versus Six Cycles of Cisplatin-based Chemotherapy in Metastatic Urothelial Carcinoma</brief_title>
  <acronym>FOCUS</acronym>
  <official_title>Four Cycles of Cisplatin-Based Chemotherapy in Metastatic Urothelial Carcinoma Compared to Six Cycles: Randomized Phase III Trial - FOCUS Study -</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Asan Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Korean Cancer Study Group</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Asan Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective is to show non-inferiority of overall survival between four cycles and six&#xD;
      cycles of first-line cisplatin based chemotherapy to determine the optimal duration of&#xD;
      chemotherapy in patients with advanced urothelial carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Urothelial carcinoma is the fifth most common cancer in men and seventh among women all&#xD;
      around the world. Although a complete surgical resection with or without perioperative&#xD;
      treatment is the most effective way to offer a potentially curative therapy to patients with&#xD;
      these cancers, 25% of the patients initially present with locally or systemically advanced&#xD;
      disease. Systemic chemotherapy is the only current modality that provides the potential for a&#xD;
      long-term survival in patients with advanced or metastatic urothelial disease.&#xD;
&#xD;
      Cisplatin based combination chemotherapies such as GP, GP-S, MVAC, and dose dense MVAC with&#xD;
      G-CSF supports are regarded as a backbone treatment for patients with advanced bladder cancer&#xD;
      on the basis of the results from previous studies.&#xD;
&#xD;
      However, there is no consensus on appropriate number of chemotherapy cycles. In phase III&#xD;
      trial comparing MVAC with GP, patients were treated with 6 cycles (every 4 weeks) of&#xD;
      chemotherapy. In another phase III trial comparing MVAC with HD-MVAC, there is no&#xD;
      pre-determined number of cycles, but the median number of cycles were 4 for MVAC and 6 for&#xD;
      HD-MVAC.&#xD;
&#xD;
      However, it is hard to complete six or more cycles of cisplatin based chemotherapy due to&#xD;
      cumulative toxicities of cisplatin such as neuropathy and development of resistance. The&#xD;
      median age of patients with urothelial cancer is 70 years old and significant proportion of&#xD;
      the patients already showed impaired performance status (ECOG PS ≥2).&#xD;
&#xD;
      There has already been reported in several trials of NSCLC, which showed that 4 cycles of&#xD;
      chemotherapy containing cisplatin has no significant differences in survival or QoL with&#xD;
      lower incidences of toxicities compared with 6 cycles of chemotherapy.&#xD;
&#xD;
      The objective of this trial is to assess whether there is any difference in OS between&#xD;
      patients who are treated with four cycles of cisplatin based chemotherapy and patients who&#xD;
      are treated with 6 cycles of chemotherapy to determine the optimal duration of chemotherapy&#xD;
      in patients with advanced urothelial cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2016</start_date>
  <completion_date type="Anticipated">February 2022</completion_date>
  <primary_completion_date type="Anticipated">August 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>5 years</time_frame>
    <description>Overall survival is defined as the time from enrollment of study until death from any cause (or date of last follow-up for patients still alive)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Every 6-8 weeks, from date of enrollment until the date of first documented progression</time_frame>
    <description>PFS is defined as the time from enrollment of study until either first documentation of RECIST-defined disease progression or death due to any cause, whichever come first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response rate</measure>
    <time_frame>Every 6-8 weeks, assess the tumor response from date of enrollment</time_frame>
    <description>Tumor response rate is defined as the proportion of patients with a complete response (CR) or partial response (PR) among patients with evaluable lesions for response of RECIST.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>safety using NCI Common Terminology Criteria for Adverse Events (version 4.03)</measure>
    <time_frame>Every 2-4 weeks, from date of enrollment until 30th days of last cycles treatment or initation of new regimen</time_frame>
    <description>Toxicity profiles will be evaluated every cycle with physical examination, vital signs, performance status, CBC, and serum chemistry using NCI Common Terminology Criteria for Adverse Events version 4.03.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life composite score of EORTC-QoL-C30 and EORTC CIPN20</measure>
    <time_frame>0-1 week, 12-18 week, 24-34 week after enrollment</time_frame>
    <description>Investigators measured Quality of life using EORTC-QoL-C30 and EORTC CIPN20 at the time of enrollment, 12-18 weeks, and 30 weeks</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">330</enrollment>
  <condition>Bladder Cancer</condition>
  <condition>Ureter Cancer</condition>
  <condition>Urethral Cancer</condition>
  <condition>Transitional Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>6 cycles arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients without evidence of disease progression or unacceptable toxicities after completion of two or four treatment cycles of cisplatin based chemotherapy (GP, GP-S, MVAC, HD-MVAC with GCSF) were randomly assigned to receive additional two to four cycles of chemotherapy (totally six cycles)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4 cycles arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients without evidence of disease progression or unacceptable toxicities after completion of two or four treatment cycles of cisplatin based chemotherapy (GP, GP-S, MVAC, HD-MVAC with GCSF) were randomly assigned to receive additional zero to two cycles of chemotherapy (totally four cycles)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment duration of cisplatin based chemotherapy</intervention_name>
    <description>GP regimen: Gemcitabine (1000 mg/m2 D1, D8), Cisplatin (60 mg/m2 D1), every 3 weeks&#xD;
GP-S regimen: Gemcitabine (1000 mg/m2 D1, D8), Cisplatin (35 mg/m2 D1,D 2 or D8), every 3 weeks&#xD;
MVAC regimen: Methotrexate (30 mg/m2 IV bolus, D1, 15, 22), Vinblastine (3 mg/m2 IV bolus, D2, 15, 22), Doxorubicin (30 mg/m2 IV bolus D2), Cisplatin (70 mg/m2 D2), every 4 weeks&#xD;
HD-MVAC with GCSF regimen: Methotrexate (30 mg/m2 IV bolus, D1), Vinblastine (3 mg/m2 IV bolus, D2), Doxorubicin (30 mg/m2 IV bolus D2), Cisplatin (70 mg/m2 D2), G-CSF (240 ug/m2 SC, D4-10), every 2 weeks</description>
    <arm_group_label>4 cycles arm</arm_group_label>
    <arm_group_label>6 cycles arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Patients with histologically or cytologically confirmed urothelial cancer&#xD;
&#xD;
          2. Unresectable locally advanced (T3b, N2-3), metastatic (M1), or recurrent disease&#xD;
&#xD;
          3. Age 18 years or older&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group performance status 0-1&#xD;
&#xD;
          5. Not progressed disease status after 2 or 4 cycles of platinum-based chemotherapy&#xD;
&#xD;
          6. Adequate organ and bone marrow function for chemotherapy&#xD;
&#xD;
          7. No history of radiation therapy, or radiation field within 25% of whole marrow would&#xD;
             be allowed. If patients underwent radiation therapy in entire pelvis, they are&#xD;
             excluded to this study. Patients should discontinue radiation therapy at least 4 weeks&#xD;
             before enrollment, and the patients should be recovered from radiation therapy&#xD;
             associated adverse events.&#xD;
&#xD;
          8. Women should use contraceptive medication for 6 months after the end of the study or&#xD;
             she would be post-menopause status. Men should consent with the contraception for 6&#xD;
             months after the end of the study or he would be infertile.&#xD;
&#xD;
          9. Patients should sign a written informed consent before study entry.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Histologic types other than urothelial cell carcinoma should be excluded. However,&#xD;
             urothelial cell types combined with squamous or glandular features are allowed.&#xD;
&#xD;
          2. Patients who showed progressed disease status after 2 or 4 cycles of platinum-based&#xD;
             chemotherapy, cannot be treated with additional chemotherapy due to adverse events, or&#xD;
             already undertook with reduced dose of more than 50%&#xD;
&#xD;
          3. Presence or history of CNS metastasis&#xD;
&#xD;
          4. Prior systemic chemotherapy (But prior intravesical chemotherapy or immunotherapy was&#xD;
             allowed, and recurrent disease after adjuvant or neoadjuvant cisplatin-based systemic&#xD;
             chemotherapy is allowed if the last chemotherapy was administered 1 year or more&#xD;
             before the patient enrollment)&#xD;
&#xD;
          5. Peripheral sensory neuropathy grade 2 or worse according to NCI CTCAE&#xD;
&#xD;
          6. History of treatment with drugs of another clinical trial within 30 days before&#xD;
             enrollment.&#xD;
&#xD;
          7. Concomitant severe medical, surgical, or psychiatric disease or problems which can&#xD;
             affect the results of the clinical trial or have possibilities of unexpected medical&#xD;
             problems caused be the drug of clinical trial&#xD;
&#xD;
          8. History of another malignancy (but treated malignancy at least two years before&#xD;
             enrollment were allowed, and cured non-melanoma skin cancer, any cured in-situ&#xD;
             carcinoma, clinically insignificant localized prostate cancer, or papillary thyroid&#xD;
             carcinoma are allowed even diagnosed less than 2 years before enrollment).&#xD;
&#xD;
          9. Pregnant or lactating women, women of childbearing potential not employing adequate&#xD;
             contraception&#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>Jae-Lyun Lee, MD., PhD.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Asan Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jae lyun Lee, MD., PhD.</last_name>
    <phone>+82-2-3010-5977</phone>
    <email>jaelyun@amc.seoul.kr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>MiRan Kim</last_name>
    <phone>+82-2-3010-5576</phone>
    <email>crnonc12@amc.seoul.kr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Kwonoh Park</name>
      <address>
        <city>Yangsan</city>
        <state>Gyeongsangnam-do</state>
        <zip>50612</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kwonoh Park, MD, PhD</last_name>
      <phone>1033783529</phone>
      <email>parkkoh@daum.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hallym University Medical Center, Hallym University College of Medicine</name>
      <address>
        <city>Anyang</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ho Young Kim</last_name>
      <email>ksfam@daum.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Fatima Hospital</name>
      <address>
        <city>Daegu</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jung Lim Lee</last_name>
      <email>junglim3@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Keimyeong University Dongsan Medical Center</name>
      <address>
        <city>Daegu</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jin Young Kim, MD</last_name>
      <email>takgu@dsmc.or.kr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Chungnam University Hospital</name>
      <address>
        <city>Daejeon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hyo Jin Lee, MD, PhD.</last_name>
      <email>cymed@cnu.ac.kr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Health Insurance Service Ilsan Hospital</name>
      <address>
        <city>Goyang</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Soo Jung Hong</last_name>
      <email>suzzy901@nhimc.or.kr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Gil Medical Center</name>
      <address>
        <city>Incheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Inkeun Park, MD, PhD</last_name>
      <email>ingni79@hanmail.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Inje University Haeundae Paik Hospital</name>
      <address>
        <city>Pusan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Il-Hwan Kim</last_name>
      <email>onelement@daum.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kosin University Hospital</name>
      <address>
        <city>Pusan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sung-Hoon Shin</last_name>
      <email>ssh1533@daum.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Pusan National University Hospital, Pusan National University School of Medicine</name>
      <address>
        <city>Pusan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hyo Jung Kim</last_name>
      <email>leonkim80@naver.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jae-Lyun Lee, MD, PhD</last_name>
      <email>jaelyun@amc.seoul.kr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Chung Ang University Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hee Joon Kim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Inje University Sanggye Paik Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Byeong Seok Sohn</last_name>
      <email>imbs@paik.ac.kr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yun-Gyoo Lee</last_name>
      <email>gosciny@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yoon Ji Choi</last_name>
      <email>yoonji23@hanmail.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bhum Suk Keam</last_name>
    </contact>
    <contact_backup>
      <email>bhumsuk@snu.ac.kr</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>VHS medical center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bong-Seog Kim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Yonsei Cancer Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sang Joon Shin</last_name>
      <email>ssj338@yuhs.ac</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>St. Vincent's Hospital, The Catholic University of Korea</name>
      <address>
        <city>Suwon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Byoung Yong Shim</last_name>
      <email>shimby@catholic.ac.kr</email>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <results_reference>
    <citation>Cheng T. Systemic therapy for unresectable and metastatic transitional cell carcinoma of the urothelium: first-line and beyond. Curr Opin Support Palliat Care. 2008 Sep;2(3):153-60. doi: 10.1097/SPC.0b013e328309c72c.</citation>
    <PMID>18685414</PMID>
  </results_reference>
  <results_reference>
    <citation>von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. doi: 10.1200/JCO.2000.18.17.3068.</citation>
    <PMID>11001674</PMID>
  </results_reference>
  <results_reference>
    <citation>Sternberg CN, de Mulder P, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, Witjes JA, Spina M, van Groeningen CJ, Duclos B, Roberts JT, de Balincourt C, Collette L; EORTC Genito-Urinary Cancer Group. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006 Jan;42(1):50-4. doi: 10.1016/j.ejca.2005.08.032. Epub 2005 Dec 5.</citation>
    <PMID>16330205</PMID>
  </results_reference>
  <results_reference>
    <citation>Loehrer PJ Sr, Einhorn LH, Elson PJ, Crawford ED, Kuebler P, Tannock I, Raghavan D, Stuart-Harris R, Sarosdy MF, Lowe BA, et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1992 Jul;10(7):1066-73. doi: 10.1200/JCO.1992.10.7.1066. Erratum In: J Clin Oncol 1993 Feb;11(2):384.</citation>
    <PMID>1607913</PMID>
  </results_reference>
  <results_reference>
    <citation>Kim YR, Lee JL, You D, Jeong IG, Song C, Hong B, Hong JH, Ahn H. Gemcitabine plus split-dose cisplatin could be a promising alternative to gemcitabine plus carboplatin for cisplatin-unfit patients with advanced urothelial carcinoma. Cancer Chemother Pharmacol. 2015 Jul;76(1):141-53. doi: 10.1007/s00280-015-2774-z. Epub 2015 May 23.</citation>
    <PMID>26001531</PMID>
  </results_reference>
  <results_reference>
    <citation>Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS, Cho EK, Yang SH, Choi JH, Heo DS, Park SY, Shin SW, Ahn MJ, Lee JS, Yun YH, Lee JW, Park K. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007 Nov 20;25(33):5233-9. doi: 10.1200/JCO.2007.10.8134.</citation>
    <PMID>18024869</PMID>
  </results_reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 22, 2016</study_first_submitted>
  <study_first_submitted_qc>September 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>September 23, 2017</last_update_submitted>
  <last_update_submitted_qc>September 23, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Asan Medical Center</investigator_affiliation>
    <investigator_full_name>Jae-Lyun Lee</investigator_full_name>
    <investigator_title>Associated Professor</investigator_title>
  </responsible_party>
  <keyword>urothelial carcinoma</keyword>
  <keyword>cisplatin</keyword>
  <keyword>first-line chemotherapy</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>Urethral Neoplasms</mesh_term>
    <mesh_term>Ureteral Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cisplatin</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/NCT03296306
org study id: KCSG GU16-02
nct id: NCT03296306
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objective is to show non-inferiority of overall survival between four cycles and six
      cycles of first-line cisplatin based chemotherapy to determine the optimal duration of
      chemotherapy in patients with advanced urothelial carcinoma.
Urothelial carcinoma is the fifth most common cancer in men and seventh among women all
      around the world. Although a complete surgical resection with or without perioperative
      treatment is the most effective way to offer a potentially curative therapy to patients with
      these cancers, 25% of the patients initially present with locally or systemically advanced
      disease. Systemic chemotherapy is the only current modality that provides the potential for a
      long-term survival in patients with advanced or metastatic urothelial disease.

      Cisplatin based combination chemotherapies such as GP, GP-S, MVAC, and dose dense MVAC with
      G-CSF supports are regarded as a backbone treatment for patients with advanced bladder cancer
      on the basis of the results from previous studies.

      However, there is no consensus on appropriate number of chemotherapy cycles. In phase III
      trial comparing MVAC with GP, patients were treated with 6 cycles (every 4 weeks) of
      chemotherapy. In another phase III trial comparing MVAC with HD-MVAC, there is no
      pre-determined number of cycles, but the median number of cycles were 4 for MVAC and 6 for
      HD-MVAC.

      However, it is hard to complete six or more cycles of cisplatin based chemotherapy due to
      cumulative toxicities of cisplatin such as neuropathy and development of resistance. The
      median age of patients with urothelial cancer is 70 years old and significant proportion of
      the patients already showed impaired performance status (ECOG PS ≥2).

      There has already been reported in several trials of NSCLC, which showed that 4 cycles of
      chemotherapy containing cisplatin has no significant differences in survival or QoL with
      lower incidences of toxicities compared with 6 cycles of chemotherapy.

      The objective of this trial is to assess whether there is any difference in OS between
      patients who are treated with four cycles of cisplatin based chemotherapy and patients who
      are treated with 6 cycles of chemotherapy to determine the optimal duration of chemotherapy
      in patients with advanced urothelial cancer.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: 5 years
description: Overall survival is defined as the time from enrollment of study until death from any cause (or date of last follow-up for patients still alive)
measure: Progression free survival
time frame: Every 6-8 weeks, from date of enrollment until the date of first documented progression
description: PFS is defined as the time from enrollment of study until either first documentation of RECIST-defined disease progression or death due to any cause, whichever come first.
measure: Tumor response rate
time frame: Every 6-8 weeks, assess the tumor response from date of enrollment
description: Tumor response rate is defined as the proportion of patients with a complete response (CR) or partial response (PR) among patients with evaluable lesions for response of RECIST.
measure: safety using NCI Common Terminology Criteria for Adverse Events (version 4.03)
time frame: Every 2-4 weeks, from date of enrollment until 30th days of last cycles treatment or initation of new regimen
description: Toxicity profiles will be evaluated every cycle with physical examination, vital signs, performance status, CBC, and serum chemistry using NCI Common Terminology Criteria for Adverse Events version 4.03.
measure: Quality of life composite score of EORTC-QoL-C30 and EORTC CIPN20
time frame: 0-1 week, 12-18 week, 24-34 week after enrollment
description: Investigators measured Quality of life using EORTC-QoL-C30 and EORTC CIPN20 at the time of enrollment, 12-18 weeks, and 30 weeks
arm group label: 6 cycles arm
arm group type: Active Comparator
description: Patients without evidence of disease progression or unacceptable toxicities after completion of two or four treatment cycles of cisplatin based chemotherapy (GP, GP-S, MVAC, HD-MVAC with GCSF) were randomly assigned to receive additional two to four cycles of chemotherapy (totally six cycles)
arm group label: 4 cycles arm
arm group type: Experimental
description: Patients without evidence of disease progression or unacceptable toxicities after completion of two or four treatment cycles of cisplatin based chemotherapy (GP, GP-S, MVAC, HD-MVAC with GCSF) were randomly assigned to receive additional zero to two cycles of chemotherapy (totally four cycles)
intervention type: Drug
intervention name: Treatment duration of cisplatin based chemotherapy
description: GP regimen: Gemcitabine (1000 mg/m2 D1, D8), Cisplatin (60 mg/m2 D1), every 3 weeks
GP-S regimen: Gemcitabine (1000 mg/m2 D1, D8), Cisplatin (35 mg/m2 D1,D 2 or D8), every 3 weeks
MVAC regimen: Methotrexate (30 mg/m2 IV bolus, D1, 15, 22), Vinblastine (3 mg/m2 IV bolus, D2, 15, 22), Doxorubicin (30 mg/m2 IV bolus D2), Cisplatin (70 mg/m2 D2), every 4 weeks
HD-MVAC with GCSF regimen: Methotrexate (30 mg/m2 IV bolus, D1), Vinblastine (3 mg/m2 IV bolus, D2), Doxorubicin (30 mg/m2 IV bolus D2), Cisplatin (70 mg/m2 D2), G-CSF (240 ug/m2 SC, D4-10), every 2 weeks
arm group label: 4 cycles arm
arm group label: 6 cycles arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jae-Lyun Lee, MD., PhD.
role: Principal Investigator
affiliation: Asan Medical Center
last name: Jae lyun Lee, MD., PhD.
phone: +82-2-3010-5977
email: jaelyun@amc.seoul.kr
last name: MiRan Kim
phone: +82-2-3010-5576
email: crnonc12@amc.seoul.kr
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country: Korea, Republic of
citation: Cheng T. Systemic therapy for unresectable and metastatic transitional cell carcinoma of the urothelium: first-line and beyond. Curr Opin Support Palliat Care. 2008 Sep;2(3):153-60. doi: 10.1097/SPC.0b013e328309c72c.
PMID: 18685414
citation: von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. doi: 10.1200/JCO.2000.18.17.3068.
PMID: 11001674
citation: Sternberg CN, de Mulder P, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, Witjes JA, Spina M, van Groeningen CJ, Duclos B, Roberts JT, de Balincourt C, Collette L; EORTC Genito-Urinary Cancer Group. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006 Jan;42(1):50-4. doi: 10.1016/j.ejca.2005.08.032. Epub 2005 Dec 5.
PMID: 16330205
citation: Loehrer PJ Sr, Einhorn LH, Elson PJ, Crawford ED, Kuebler P, Tannock I, Raghavan D, Stuart-Harris R, Sarosdy MF, Lowe BA, et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1992 Jul;10(7):1066-73. doi: 10.1200/JCO.1992.10.7.1066. Erratum In: J Clin Oncol 1993 Feb;11(2):384.
PMID: 1607913
citation: Kim YR, Lee JL, You D, Jeong IG, Song C, Hong B, Hong JH, Ahn H. Gemcitabine plus split-dose cisplatin could be a promising alternative to gemcitabine plus carboplatin for cisplatin-unfit patients with advanced urothelial carcinoma. Cancer Chemother Pharmacol. 2015 Jul;76(1):141-53. doi: 10.1007/s00280-015-2774-z. Epub 2015 May 23.
PMID: 26001531
citation: Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS, Cho EK, Yang SH, Choi JH, Heo DS, Park SY, Shin SW, Ahn MJ, Lee JS, Yun YH, Lee JW, Park K. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007 Nov 20;25(33):5233-9. doi: 10.1200/JCO.2007.10.8134.
PMID: 18024869
responsible party type: Principal Investigator
investigator affiliation: Asan Medical Center
investigator full name: Jae-Lyun Lee
investigator title: Associated Professor
mesh term: Carcinoma
mesh term: Carcinoma, Transitional Cell
mesh term: Urethral Neoplasms
mesh term: Ureteral Neoplasms
mesh term: Cisplatin
sharing ipd: Undecided