<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/NCT01714037</url>
  </required_header>
  <id_info>
    <org_study_id>Debio 0932-201</org_study_id>
    <nct_id>NCT01714037</nct_id>
  </id_info>
  <brief_title>A Clinical Study on the Safety and Efficacy of Debio 0932 in Combination With Standard of Care in Patients With Non-small Cell Lung Cancer [NSCLC]</brief_title>
  <acronym>HALO</acronym>
  <official_title>A Phase I-II Evaluation of the Safety and Efficacy of the Oral HSP90 Inhibitor Debio 0932 in Combination With Standard of Care in first-and Second-line Therapy of Patients With Stage IIIb or IV Non-small Cell Lung Cancer-the HALO Study (HSP90 Inhibition And Lung Cancer Outcomes)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Debiopharm International SA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Syneos Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Debiopharm International SA</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Part A of this study will investigate the Maximum Tolerated Dose of Debio 0932 in combination&#xD;
      with standard of care chemotherapy for the first- and second-line treatment of advanced&#xD;
      NSCLC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Part A of this study will determine the Maximum Tolerated Dose of Debio 0932 in combination&#xD;
      with cisplatin/pemetrexed and cisplatin/gemcitabine in treatment-naïve patients with Stage&#xD;
      IIIb or IV NSCLC, and with docetaxel in previously treated patients with Stage IIIb or IV&#xD;
      NSCLC.&#xD;
&#xD;
      Escalating doses of Debio 0932 will be given to subsequent patients in combination with&#xD;
      standard doses of these 3 background chemotherapies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">November 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of Dose Limiting Toxicities</measure>
    <time_frame>6 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in vital signs and Eastern Cooperative Oncology Group Performance Status (ECOG PS)</measure>
    <time_frame>Day 1 of each treatment cycle until disease progression or study drug toxicity</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Every treatment cycle until disease progression or study drug toxicity</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of laboratory abnormalities</measure>
    <time_frame>2 to 4 times every treatment cycle until disease progression or study drug toxicity</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment discontinuations due to AEs and SAEs</measure>
    <time_frame>Every treatment cycle until diseases progression or study drug toxicity</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in left ventricular ejection fraction (LVEF)</measure>
    <time_frame>Baseline and after 4 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters of Debio 0932 and its metabolite Debio 0932-MET1</measure>
    <time_frame>22 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters of cisplatin/pemetrexed, cisplatin/gemcitabine, and docetaxel</measure>
    <time_frame>22 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best overall tumor response</measure>
    <time_frame>22 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic biomarkers</measure>
    <time_frame>22 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacogenomic, tumour pharmacogenetic, proteomic, and pharmacogenetic factors predictive of response to Debio 0932</measure>
    <time_frame>7 days</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Cisplatin, Pemetrexed, Debio 0932</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cisplatin, Pemetrexed, Debio 0932</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cisplatin, Gemcitabine, Debio 0932</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cisplatin, Gemcitabine, Debio 0932</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Docetaxel, Debio 0932</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Docetaxel, Debio 0932</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Debio 0932</intervention_name>
    <description>Debio 0932 will be administered as daily oral tablets at a starting dose of 250 mg four times per day (QD).</description>
    <arm_group_label>Cisplatin, Gemcitabine, Debio 0932</arm_group_label>
    <arm_group_label>Cisplatin, Pemetrexed, Debio 0932</arm_group_label>
    <arm_group_label>Docetaxel, Debio 0932</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Cisplatin 75 mg/m2 body surface area (BSA) will be administered on Day 1 of each 21-day treatment cycle.</description>
    <arm_group_label>Cisplatin, Gemcitabine, Debio 0932</arm_group_label>
    <arm_group_label>Cisplatin, Pemetrexed, Debio 0932</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>Pemetrexed 500 mg/m2 BSA will be administered on Day 1 of each 21 day treatment cycle.</description>
    <arm_group_label>Cisplatin, Pemetrexed, Debio 0932</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Gemcitabine 1250 mg/m2 BSA will be administered on Days 1 and 8 of each 21-day treatment cycle.</description>
    <arm_group_label>Cisplatin, Gemcitabine, Debio 0932</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>Docetaxel 60 or 75 mg/m2 BSA will be administered on Day 1 of each 21-day treatment cycle.</description>
    <arm_group_label>Docetaxel, Debio 0932</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of NSCLC with confirmed squamous or non-squamous tumour histology, without&#xD;
             known epidermal growth factor receptor (EGFR) mutation&#xD;
&#xD;
          -  Advanced or metastatic disease (Stage IIIb or IV)&#xD;
&#xD;
          -  Patients to be treated with cisplatin/gemcitabine or cisplatin/pemetrexed: No previous&#xD;
             systemic treatment with chemotherapy, targeted therapy or investigational agents&#xD;
             (except adjuvant therapy if &gt; 6 months ago); Patients to be treated with docetaxel: ≥&#xD;
             1 previous treatment with chemotherapy&#xD;
&#xD;
          -  Measurable disease by the Response Evaluation Criteria in Solid Tumors (RECIST)&#xD;
             criteria&#xD;
&#xD;
          -  ECOG performance score 0-1&#xD;
&#xD;
          -  Life expectancy ≥ 3 months&#xD;
&#xD;
          -  Adequate bone marrow-, renal- and hepatic function&#xD;
&#xD;
          -  LVEF ≥ 55% on cardiac ultrasound&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Symptomatic brain metastases&#xD;
&#xD;
          -  Gastro-intestinal disorders that could affect drug absorption (including, but not&#xD;
             limited to, major abdominal surgery, significant bowel obstruction, ulcerative&#xD;
             colitis, Crohn's disease)&#xD;
&#xD;
          -  Concurrent treatment with any other systemic anti-cancer therapy&#xD;
&#xD;
          -  Serious concomitant uncontrolled medical conditions&#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>Nicolas Isambert, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre GF Leclerc, Dijon, France</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jean-Pierre Delord, PR</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut Claudius Regaud, Toulouse, France</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jèrôme Fayette, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Léon Bérard, Lyon, France</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jaafar Bennouma, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut de Cancérologie de l'Ouest- Institut René Gauduchau, Nantes, France</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Luis Paz-Ares, PR</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitario Virgen del Rocío, Seville, Spain</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Enriqueta Felip, PR</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Universitari Vall d'Hebron, Barcelone, Spain</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mariano Provencio, PR</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Puerta de Hierro Majadahonda, Madrid, Spain</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ruth Plummer, PR</last_name>
    <role>Principal Investigator</role>
    <affiliation>Freeman Hospital, Newcastle, UK</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre GF Leclerc</name>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Léon Bérard</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de l'Ouest- Institut René Gauduchau</name>
      <address>
        <city>Nantes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Claudius Regaud</name>
      <address>
        <city>Toulouse</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Puerta de Hierro Majadahonda</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Seville</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Freeman Hospital</name>
      <address>
        <city>Newcastle</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Spain</country>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://www.debiopharm.com</url>
    <description>Site Debiopharm SA</description>
  </link>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>October 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 25, 2012</study_first_posted>
  <last_update_submitted>April 7, 2015</last_update_submitted>
  <last_update_submitted_qc>April 7, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 8, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Safety</keyword>
  <keyword>Efficacy</keyword>
  <keyword>HSP90</keyword>
  <keyword>Debio 0932</keyword>
  <keyword>Standard of care treatment, NSCLC</keyword>
  <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>Gemcitabine</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01714037
org study id: Debio 0932-201
nct id: NCT01714037
lead sponsor: 
collaborator: 
has dmc: No
Part A of this study will investigate the Maximum Tolerated Dose of Debio 0932 in combination
      with standard of care chemotherapy for the first- and second-line treatment of advanced
      NSCLC.
Part A of this study will determine the Maximum Tolerated Dose of Debio 0932 in combination
      with cisplatin/pemetrexed and cisplatin/gemcitabine in treatment-naïve patients with Stage
      IIIb or IV NSCLC, and with docetaxel in previously treated patients with Stage IIIb or IV
      NSCLC.

      Escalating doses of Debio 0932 will be given to subsequent patients in combination with
      standard doses of these 3 background chemotherapies.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of Dose Limiting Toxicities
time frame: 6 weeks
measure: Change in vital signs and Eastern Cooperative Oncology Group Performance Status (ECOG PS)
time frame: Day 1 of each treatment cycle until disease progression or study drug toxicity
measure: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Every treatment cycle until disease progression or study drug toxicity
measure: Incidence of laboratory abnormalities
time frame: 2 to 4 times every treatment cycle until disease progression or study drug toxicity
measure: Incidence of treatment discontinuations due to AEs and SAEs
time frame: Every treatment cycle until diseases progression or study drug toxicity
measure: Change in left ventricular ejection fraction (LVEF)
time frame: Baseline and after 4 weeks of treatment
measure: Pharmacokinetic parameters of Debio 0932 and its metabolite Debio 0932-MET1
time frame: 22 days
measure: Pharmacokinetic parameters of cisplatin/pemetrexed, cisplatin/gemcitabine, and docetaxel
time frame: 22 days
measure: Best overall tumor response
time frame: 22 days
measure: Pharmacodynamic biomarkers
time frame: 22 days
measure: Pharmacogenomic, tumour pharmacogenetic, proteomic, and pharmacogenetic factors predictive of response to Debio 0932
time frame: 7 days
arm group label: Cisplatin, Pemetrexed, Debio 0932
arm group type: Experimental
description: Cisplatin, Pemetrexed, Debio 0932
arm group label: Cisplatin, Gemcitabine, Debio 0932
arm group type: Experimental
description: Cisplatin, Gemcitabine, Debio 0932
arm group label: Docetaxel, Debio 0932
arm group type: Experimental
description: Docetaxel, Debio 0932
intervention type: Drug
intervention name: Debio 0932
description: Debio 0932 will be administered as daily oral tablets at a starting dose of 250 mg four times per day (QD).
arm group label: Cisplatin, Gemcitabine, Debio 0932
arm group label: Cisplatin, Pemetrexed, Debio 0932
arm group label: Docetaxel, Debio 0932
intervention type: Drug
intervention name: Cisplatin
description: Cisplatin 75 mg/m2 body surface area (BSA) will be administered on Day 1 of each 21-day treatment cycle.
arm group label: Cisplatin, Gemcitabine, Debio 0932
arm group label: Cisplatin, Pemetrexed, Debio 0932
intervention type: Drug
intervention name: Pemetrexed
description: Pemetrexed 500 mg/m2 BSA will be administered on Day 1 of each 21 day treatment cycle.
arm group label: Cisplatin, Pemetrexed, Debio 0932
intervention type: Drug
intervention name: Gemcitabine
description: Gemcitabine 1250 mg/m2 BSA will be administered on Days 1 and 8 of each 21-day treatment cycle.
arm group label: Cisplatin, Gemcitabine, Debio 0932
intervention type: Drug
intervention name: Docetaxel
description: Docetaxel 60 or 75 mg/m2 BSA will be administered on Day 1 of each 21-day treatment cycle.
arm group label: Docetaxel, Debio 0932
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nicolas Isambert, MD
role: Principal Investigator
affiliation: Centre GF Leclerc, Dijon, France
last name: Jean-Pierre Delord, PR
role: Principal Investigator
affiliation: Institut Claudius Regaud, Toulouse, France
last name: Jèrôme Fayette, MD
role: Principal Investigator
affiliation: Centre Léon Bérard, Lyon, France
last name: Jaafar Bennouma, MD
role: Principal Investigator
affiliation: Institut de Cancérologie de l'Ouest- Institut René Gauduchau, Nantes, France
last name: Luis Paz-Ares, PR
role: Principal Investigator
affiliation: Hospital Universitario Virgen del Rocío, Seville, Spain
last name: Enriqueta Felip, PR
role: Principal Investigator
affiliation: Hospital Universitari Vall d'Hebron, Barcelone, Spain
last name: Mariano Provencio, PR
role: Principal Investigator
affiliation: Hospital Puerta de Hierro Majadahonda, Madrid, Spain
last name: Ruth Plummer, PR
role: Principal Investigator
affiliation: Freeman Hospital, Newcastle, UK
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
country: Spain
country: United Kingdom
url: http://www.debiopharm.com
description: Site Debiopharm SA
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Gemcitabine
mesh term: Docetaxel
mesh term: Pemetrexed