<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/NCT02204345</url>
  </required_header>
  <id_info>
    <org_study_id>BP29360</org_study_id>
    <secondary_id>2014-001498-15</secondary_id>
    <nct_id>NCT02204345</nct_id>
  </id_info>
  <brief_title>A Study Evaluating RO5479599 in Combination With Carboplatin and Paclitaxel in Participants With Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC) of Squamous Histology</brief_title>
  <official_title>Open Label Phase Ib/II, Multicenter Study of the Combination of RO5479599 With Carboplatin and Paclitaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) of Squamous Histology Who Have Not Received Prior Chemotherapy or Targeted Therapy for NSCLC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <brief_summary>
    <textblock>
      A multi-center Phase Ib/II study of the combination of RO5479599 with carboplatin and&#xD;
      paclitaxel once in every 3 week (q3w) regimen to evaluate the safety and tolerability.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</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>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>Percentage of Participants With Adverse Events</measure>
    <time_frame>Baseline up to Day 342</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Objective Response as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)</measure>
    <time_frame>Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) as Assessed Using RECIST v1.1</measure>
    <time_frame>Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Disease Control as Assessed by Investigator Using RECIST v1.1</measure>
    <time_frame>Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RO5479599</measure>
    <time_frame>Pre-dose(Hour 0); at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to end of treatment (EOT, Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of RO5479599</measure>
    <time_frame>Pre-dose (Hour 0) and at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to EOT (Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough Concentration (Ctrough) of RO5479599</measure>
    <time_frame>Pre-dose (Hour 0) on Day 1 of each cycle (cycle length = 21 days) up to EOT (Day 314)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Clearance (CL) of RO5479599</measure>
    <time_frame>Pre-dose (Hour 0) and at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to EOT (Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution at Steady State (Vss) of RO5479599</measure>
    <time_frame>Pre-dose (Hour 0) and at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to EOT (Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio (Rac) of RO5479599</measure>
    <time_frame>Pre-dose(Hour 0); at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to end of treatment (EOT, Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Elimination Half-life (t 1/2) of RO5479599</measure>
    <time_frame>Pre-dose(Hour 0); at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to end of treatment (EOT, Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of RO5479599 at the Time of Tumor Progression (Cprog)</measure>
    <time_frame>At tumor progression (any time between Baseline and Day 342)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of RO5479599 at the Time of Tumor Response (Complete Response or Partial Response)</measure>
    <time_frame>At the time of tumor response (anytime between baseline and Day 342)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of RO5479599 at the Time of Toxicity</measure>
    <time_frame>At the time of toxicity (anytime between baseline and Day 342)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of RO5479599 at the Time of Infusion-related Reactions (IRRs) or Hypersensitivity Reaction</measure>
    <time_frame>At the time of IRRs or Hypersensitivity Reaction (anytime between baseline and Day 342)</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Squamous Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>RO5479599 + Carboplatin + Paclitaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>RO5479599 800 milligrams (mg) will be administered in the Safety Run-In Phase by intravenous infusion q3w on Day 1 of 3-weekly cycles (each cycle of 21 days) in combination with carboplatin (to produce an area under the curve [AUC] of 6 mg/milliliter [mL]*minute) and paclitaxel 200 mg per square meter (mg/m^2) by intravenous infusion q3w for 4 to 6 cycles. Thereafter, RO5479599 will be continued as a monotherapy (carboplatin and paclitaxel may be continued at the investigator's discretion) until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin by intravenous infusion q3w for 4-6 cycles and thereafter as per investigator's discretion.</description>
    <arm_group_label>RO5479599 + Carboplatin + Paclitaxel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Paclitaxel by intravenous infusion q3w until disease progression, death, unacceptable toxicity or withdrawal of consent.</description>
    <arm_group_label>RO5479599 + Carboplatin + Paclitaxel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RO5479599</intervention_name>
    <description>RO5479599 will be administered as an intravenous infusion q3w until disease progression, death, unacceptable toxicity or withdrawal of consent.</description>
    <arm_group_label>RO5479599 + Carboplatin + Paclitaxel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants with the Eastern Cooperative Oncology Group (ECOG) performance status&#xD;
             (PS) 0-1&#xD;
&#xD;
          -  Locally advanced or metastatic (stage IIIB or IV) squamous NSCLC&#xD;
&#xD;
          -  No prior systemic chemotherapy, targeted therapy for metastatic NSCLC&#xD;
&#xD;
          -  Evidence of at least one radiologically measurable lesion as per RECIST version 1.1&#xD;
&#xD;
          -  Adequate hematological, liver and renal function&#xD;
&#xD;
          -  Participants must agree to either remain completely abstinent or to use effective&#xD;
             contraceptive methods from screening until 6 months after the last dose of study&#xD;
             treatment&#xD;
&#xD;
          -  Histologically confirmed squamous NSCLC participants eligible for enrollment must&#xD;
             provide archival tumor biopsy tissue or if unavailable must be willing to undergo a&#xD;
             fresh pretreatment primary tumor or metastatic biopsy&#xD;
&#xD;
          -  Participants with Gilbert's Syndrome will be eligible for the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concurrent therapy with any other investigational drug&#xD;
&#xD;
          -  History or clinical evidence of central nervous system (CNS) primary tumors or&#xD;
             metastases&#xD;
&#xD;
          -  Evidence of significant, uncontrolled concomitant diseases, which could affect&#xD;
             compliance with the protocol or interpretation of results, including uncontrolled&#xD;
             diabetes mellitus and/or significant cardiovascular disease or uncontrolled infection&#xD;
&#xD;
          -  Any other diseases, metabolic dysfunction, a physical examination finding or a&#xD;
             clinical laboratory finding, giving reasonable suspicion of a disease or condition&#xD;
             that would contraindicate the use of an investigational drug&#xD;
&#xD;
          -  Major surgery or significant traumatic injury less than (&lt;) 28 days prior to the first&#xD;
             study treatment infusion (excluding biopsies) or anticipation of the need for major&#xD;
             surgery during study treatment&#xD;
&#xD;
          -  Pregnant or breast-feeding women&#xD;
&#xD;
          -  History of other malignancies that could affect compliance with protocol or&#xD;
             interpretation of results. Participants with malignancies diagnosed more than 5 years&#xD;
             prior to study day one, adequately treated carcinoma in situ of the cervix or basal or&#xD;
             squamous cell skin cancer are generally eligible&#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>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>København Ø</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Denmark</country>
    <country>Spain</country>
  </location_countries>
  <removed_countries>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>United Kingdom</country>
  </removed_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <disposition_first_submitted>January 24, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>January 24, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">January 25, 2017</disposition_first_posted>
  <last_update_submitted>January 24, 2017</last_update_submitted>
  <last_update_submitted_qc>January 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT02204345
org study id: BP29360
secondary id: 2014-001498-15
nct id: NCT02204345
lead sponsor: 
A multi-center Phase Ib/II study of the combination of RO5479599 with carboplatin and
      paclitaxel once in every 3 week (q3w) regimen to evaluate the safety and tolerability.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Adverse Events
time frame: Baseline up to Day 342
measure: Percentage of Participants With Objective Response as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
time frame: Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342)
measure: Progression-free Survival (PFS) as Assessed Using RECIST v1.1
time frame: Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342)
measure: Overall survival (OS)
time frame: Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342)
measure: Percentage of Participants With Disease Control as Assessed by Investigator Using RECIST v1.1
time frame: Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first (assessed every 6 weeks from baseline [Cycle 1 Day 1] [Cycle length = 21 days] up to Day 342)
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] of RO5479599
time frame: Pre-dose(Hour 0); at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to end of treatment (EOT, Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342
measure: Maximum Observed Plasma Concentration (Cmax) of RO5479599
time frame: Pre-dose (Hour 0) and at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to EOT (Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342
measure: Trough Concentration (Ctrough) of RO5479599
time frame: Pre-dose (Hour 0) on Day 1 of each cycle (cycle length = 21 days) up to EOT (Day 314)
measure: Total Clearance (CL) of RO5479599
time frame: Pre-dose (Hour 0) and at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to EOT (Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342
measure: Volume of Distribution at Steady State (Vss) of RO5479599
time frame: Pre-dose (Hour 0) and at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to EOT (Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342
measure: Accumulation Ratio (Rac) of RO5479599
time frame: Pre-dose(Hour 0); at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to end of treatment (EOT, Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342
measure: Terminal Elimination Half-life (t 1/2) of RO5479599
time frame: Pre-dose(Hour 0); at end of infusion (infusion duration=approximately 2 hours) on Day 1 of each cycle (cycle length= 21 days) up to end of treatment (EOT, Day 314); 3-6, 24, 72, 168, 264, 336, 432, 480 hours post-dose on Day 1 of Cycle 1,4; at Day 342
measure: Concentration of RO5479599 at the Time of Tumor Progression (Cprog)
time frame: At tumor progression (any time between Baseline and Day 342)
measure: Concentration of RO5479599 at the Time of Tumor Response (Complete Response or Partial Response)
time frame: At the time of tumor response (anytime between baseline and Day 342)
measure: Concentration of RO5479599 at the Time of Toxicity
time frame: At the time of toxicity (anytime between baseline and Day 342)
measure: Concentration of RO5479599 at the Time of Infusion-related Reactions (IRRs) or Hypersensitivity Reaction
time frame: At the time of IRRs or Hypersensitivity Reaction (anytime between baseline and Day 342)
arm group label: RO5479599 + Carboplatin + Paclitaxel
arm group type: Experimental
description: RO5479599 800 milligrams (mg) will be administered in the Safety Run-In Phase by intravenous infusion q3w on Day 1 of 3-weekly cycles (each cycle of 21 days) in combination with carboplatin (to produce an area under the curve [AUC] of 6 mg/milliliter [mL]*minute) and paclitaxel 200 mg per square meter (mg/m^2) by intravenous infusion q3w for 4 to 6 cycles. Thereafter, RO5479599 will be continued as a monotherapy (carboplatin and paclitaxel may be continued at the investigator's discretion) until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first.
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin by intravenous infusion q3w for 4-6 cycles and thereafter as per investigator's discretion.
arm group label: RO5479599 + Carboplatin + Paclitaxel
intervention type: Drug
intervention name: Paclitaxel
description: Paclitaxel by intravenous infusion q3w until disease progression, death, unacceptable toxicity or withdrawal of consent.
arm group label: RO5479599 + Carboplatin + Paclitaxel
intervention type: Drug
intervention name: RO5479599
description: RO5479599 will be administered as an intravenous infusion q3w until disease progression, death, unacceptable toxicity or withdrawal of consent.
arm group label: RO5479599 + Carboplatin + Paclitaxel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: Denmark
country: Spain
country: Korea, Republic of
country: Netherlands
country: United Kingdom
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Paclitaxel
mesh term: Carboplatin