<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/NCT01712217</url>
  </required_header>
  <id_info>
    <org_study_id>AT13387-05</org_study_id>
    <secondary_id>2012-001575-37</secondary_id>
    <nct_id>NCT01712217</nct_id>
  </id_info>
  <brief_title>A Study of AT13387 in Patients With Non-Small Cell Lung Cancer (NSCLC) Alone and in Combination With Crizotinib</brief_title>
  <official_title>A Study of HSP90 Inhibitor AT13387 Alone and in Combination With Crizotinib in the Treatment of Non-small Cell Lung Cancer (NSCLC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Astex Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Astex Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate safety and efficacy of AT13387 Alone and in&#xD;
      Combination with Crizotinib in the Treatment of Non-small Cell Lung Cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a 3-part phase 1-2 study in patients with anaplastic lymphoma kinase (ALK) + or other&#xD;
      potentially crizotinib-sensitive NSCLC who have been receiving crizotinib. Part A is a&#xD;
      single-arm, Phase 1, open-label, dose escalation design in patients with NSCLC who have&#xD;
      already been receiving crizotinib for at least 8 weeks and continue to tolerate therapy. Part&#xD;
      B is a Phase 2, open-label, randomized continuation design comparing crizotinib alone versus&#xD;
      the combination of crizotinib + AT13387 at the maximum tolerated dose established in Part A.&#xD;
      Part C is an open-label, randomized, Phase 2, Simon's 2 stage design evaluating single agent&#xD;
      AT13387 or combination AT13387 + crizotinib at the MTD established in Part A in patients who&#xD;
      progressed on crizotinib at any time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">May 16, 2017</completion_date>
  <primary_completion_date type="Actual">December 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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib.</measure>
    <time_frame>12 months</time_frame>
    <description>- Number of patients with adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: The comparison of objective response rate by RECIST 1.1 between crizotinib alone and the combination of crizotinib + AT13387.</measure>
    <time_frame>18 months</time_frame>
    <description>- Change in tumor measurements by RECIST 1.1 every 8 weeks</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part C: The objective overall response rate for AT13387 alone and the objective response rate (CR+PR) for AT13387 + crizotinib at Stage 1 and Stage 2 of the Simon's 2-stage design.</measure>
    <time_frame>18 months</time_frame>
    <description>- Change in tumor measurements by RECIST 1.1 every 8 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib</measure>
    <time_frame>12 months</time_frame>
    <description>Area under the plasma concentration versus time curve (AUC) of AT13387 and crizotinib alone and in combination Week 4&#xD;
Maximum concentration (Cmax) OF AT13387 and crizotinib alone and in combination by Week 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Assess antitumor activity of crizotinib + AT13387 combination, circulating tumor cells (CTCs) response, progression free survival (PFS) and overall survival (OS).</measure>
    <time_frame>12 months</time_frame>
    <description>Change in tumor measurements by RECIST 1.1 every 8 weeks&#xD;
Change in CTCs from baseline every 4 weeks&#xD;
Assessment of PFS and OS as measured by weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Assess safety of AT13387 in combination with crizotinib; compare PFS and OS between crizotinib and crizotinib + AT13387; and assess overall response rate (CR + PR) in crizotinib patients who crossover to crizotinib + AT13387</measure>
    <time_frame>18 months</time_frame>
    <description>Number of patients with adverse events&#xD;
PFS and OS as measured in weeks&#xD;
Response rate as measured by RECIST 1.1 every 8 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part C: Assess safety of AT13387 alone and in combination with crizotinib who progressed on crizotinib treatment; and compare the PFS and OS of AT13387 administered alone or in combination with crizotinib</measure>
    <time_frame>18 months</time_frame>
    <description>Number of patients with adverse events&#xD;
PFS and OS as measured in weeks</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">220</enrollment>
  <condition>Non-small Cell Lung Cancer(NSCLC)</condition>
  <arm_group>
    <arm_group_label>AT13387 and Crizotinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Part A is a single-arm, Phase 1, open-label, dose-escalation design in patients with NSCLC who have already been receiving crizotinib 250 mg by mouth (PO) twice daily (BID) for at least 8 weeks and are still tolerating treatment at that dose. Patients will continue treatment with crizotinib + escalating doses of AT13387 IV weekly for 3 weeks in a 4-week cycle. Each cohort will consist of at least 6 patients until the maximum tolerated dose (MTD) is reached. An additional 12 patients will be treated at the MTD level of AT13387 in combination with crizotinib to confirm the safety profile of the combination at that dose level.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Crizotinib versus crizotinib + AT13387</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Part B is a Phase 2, open-label, randomized continuation design comparing crizotinib alone versus the combination of crizotinib + AT13387 at the MTD established in Part A. Part B will enroll 128 patients with NSCLC who have been treated with crizotinib for at least 8 weeks and are still tolerating treatment without evidence of disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AT13387 or AT13387 + crizotinib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Part C is an open-label, randomized, Phase 2, Simon's 2-stage design of AT13387 administered alone once weekly for 3 weeks (QW×3) or in combination with crizotinib at the MTD established in Part A.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AT13387</intervention_name>
    <description>HSP90 inhibitor</description>
    <arm_group_label>AT13387 and Crizotinib</arm_group_label>
    <arm_group_label>AT13387 or AT13387 + crizotinib</arm_group_label>
    <arm_group_label>Crizotinib versus crizotinib + AT13387</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Crizotinib</intervention_name>
    <description>ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor</description>
    <arm_group_label>AT13387 and Crizotinib</arm_group_label>
    <arm_group_label>AT13387 or AT13387 + crizotinib</arm_group_label>
    <arm_group_label>Crizotinib versus crizotinib + AT13387</arm_group_label>
    <other_name>Xalkori</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men or women 18 years of age or older&#xD;
&#xD;
          2. Must have Non-small Cell Lung Cancer with ALK+ mutation or other mutations or&#xD;
             rearrangements potentially sensitive to crizotinib&#xD;
&#xD;
          3. Measurable disease&#xD;
&#xD;
          4. Must have been receiving or have received crizotinib&#xD;
&#xD;
          5. Have adequate cardiac, bone marrow, liver and kidney function&#xD;
&#xD;
          6. Must be willing and able to provide written informed consent and comply with the&#xD;
             protocol and study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior anti-cancer treatment with any HSP90 inhibitor&#xD;
&#xD;
          2. Have received chemotherapy, radiation therapy or other anticancer treatment other than&#xD;
             crizotinib within 3 weeks prior to the first dose of study drug&#xD;
&#xD;
          3. Prior malignancy other than adequately treated basal or squamous cell carcinoma of the&#xD;
             skin, superficial bladder cancer, low-grade cervical cancer, non-metastatic prostate&#xD;
             cancer, or have been disease-free for at least 3 years&#xD;
&#xD;
          4. Abnormal heart function&#xD;
&#xD;
          5. Presence of a life-threatening illness, medical condition, organ system dysfunction,&#xD;
             or other factors&#xD;
&#xD;
          6. Hypersensitivity of AT13387 or other components of the drug product&#xD;
&#xD;
          7. Treatment with an investigational drug within 3 weeks prior to the first dose of study&#xD;
             drug&#xD;
&#xD;
          8. Severe systemic diseases or active uncontrolled infections&#xD;
&#xD;
          9. Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis&#xD;
             C virus or hepatitis B virus&#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>Jean-Charles Soria, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Gustave Roussy, Cancer Campus, Grand Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic-Scottsdale</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Diego Medical Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093-0698</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sharp Clinical Oncology Research-Sharp Memorial Hospital</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Innovative Clinical Research Institute</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>90603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University School of Medicine-Yale Cancer Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06519</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christiana Hospital</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Hospital Cancer Institute</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center &amp; Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612-9497</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University The Feinberg School of Medicine</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Melvin and and Bren Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Medical Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barbara Ann Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic-Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center Eppley Cancer Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cone Health Cancer Center</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27409</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology in Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Cancer Institute</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Pennsylvania State University-Penn State</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033-0850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The West Clinic</name>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <zip>38138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Cancer Specialists</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Cancer Institute</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin-Carbone Cancer Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53579</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlantic Clinical Cancer Research Unit</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 1V7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Health Center</name>
      <address>
        <city>Montreal, Quebec</city>
        <zip>H3A 1A1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire de Cardiologie et de Pneumologie De Quebec</name>
      <address>
        <city>Sainte-Foy, Quebec</city>
        <zip>G1V 4G5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Hospital</name>
      <address>
        <city>Toronto, Ontario</city>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Manitoba</name>
      <address>
        <city>Winnipeg</city>
        <zip>R3E OV9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Regional Universitaire Besancon</name>
      <address>
        <city>Besancon Cedex</city>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Caen-Hopital Cote de Nacre</name>
      <address>
        <city>Caen</city>
        <zip>14033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Antoine</name>
      <address>
        <city>Creteil Cedex</city>
        <zip>94010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de Grenoble</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU de Lille</name>
      <address>
        <city>Lille cedex</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Paoli-Calmettes</name>
      <address>
        <city>Marseille</city>
        <zip>13273</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Tenon</name>
      <address>
        <city>Paris</city>
        <zip>75020</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Lyon Sud</name>
      <address>
        <city>Pierre-Benite Cedex</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Toulouse-Hopital Larrey</name>
      <address>
        <city>Toulouse</city>
        <zip>31 059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94800</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chungbuk National University Hospital</name>
      <address>
        <city>Cheongju-si</city>
        <zip>362-711</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea, St. Vincent's Hospital</name>
      <address>
        <city>Gyeonggi-do</city>
        <zip>442-723</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chonnam National University Hwasun Hospital</name>
      <address>
        <city>Hwasun-gun Jeonnam</city>
        <zip>519-809</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center</name>
      <address>
        <city>Korea</city>
        <zip>410-769</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam</city>
        <zip>463-707</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>135-710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>138-736</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Quiron Dexeus Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08028</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Integral Oncologico Clara Campal</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Regional Universitario de Malaga</name>
      <address>
        <city>Malaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>France</country>
    <country>Korea, Republic of</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>October 11, 2012</study_first_submitted>
  <study_first_submitted_qc>October 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 23, 2012</study_first_posted>
  <disposition_first_submitted>January 15, 2018</disposition_first_submitted>
  <disposition_first_submitted_qc>January 15, 2018</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 18, 2018</disposition_first_posted>
  <last_update_submitted>January 17, 2018</last_update_submitted>
  <last_update_submitted_qc>January 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non-small cell lung cancer</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>Crizotinib</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/NCT01712217
org study id: AT13387-05
secondary id: 2012-001575-37
nct id: NCT01712217
lead sponsor: 
has dmc: No
The purpose of the study is to evaluate safety and efficacy of AT13387 Alone and in
      Combination with Crizotinib in the Treatment of Non-small Cell Lung Cancer.
This is a 3-part phase 1-2 study in patients with anaplastic lymphoma kinase (ALK) + or other
      potentially crizotinib-sensitive NSCLC who have been receiving crizotinib. Part A is a
      single-arm, Phase 1, open-label, dose escalation design in patients with NSCLC who have
      already been receiving crizotinib for at least 8 weeks and continue to tolerate therapy. Part
      B is a Phase 2, open-label, randomized continuation design comparing crizotinib alone versus
      the combination of crizotinib + AT13387 at the maximum tolerated dose established in Part A.
      Part C is an open-label, randomized, Phase 2, Simon's 2 stage design evaluating single agent
      AT13387 or combination AT13387 + crizotinib at the MTD established in Part A in patients who
      progressed on crizotinib at any time.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib.
time frame: 12 months
description: - Number of patients with adverse events
measure: Part B: The comparison of objective response rate by RECIST 1.1 between crizotinib alone and the combination of crizotinib + AT13387.
time frame: 18 months
description: - Change in tumor measurements by RECIST 1.1 every 8 weeks
measure: Part C: The objective overall response rate for AT13387 alone and the objective response rate (CR+PR) for AT13387 + crizotinib at Stage 1 and Stage 2 of the Simon's 2-stage design.
time frame: 18 months
description: - Change in tumor measurements by RECIST 1.1 every 8 weeks
measure: Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib
time frame: 12 months
description: Area under the plasma concentration versus time curve (AUC) of AT13387 and crizotinib alone and in combination Week 4
Maximum concentration (Cmax) OF AT13387 and crizotinib alone and in combination by Week 4
measure: Part A: Assess antitumor activity of crizotinib + AT13387 combination, circulating tumor cells (CTCs) response, progression free survival (PFS) and overall survival (OS).
time frame: 12 months
description: Change in tumor measurements by RECIST 1.1 every 8 weeks
Change in CTCs from baseline every 4 weeks
Assessment of PFS and OS as measured by weeks
measure: Part B: Assess safety of AT13387 in combination with crizotinib; compare PFS and OS between crizotinib and crizotinib + AT13387; and assess overall response rate (CR + PR) in crizotinib patients who crossover to crizotinib + AT13387
time frame: 18 months
description: Number of patients with adverse events
PFS and OS as measured in weeks
Response rate as measured by RECIST 1.1 every 8 weeks
measure: Part C: Assess safety of AT13387 alone and in combination with crizotinib who progressed on crizotinib treatment; and compare the PFS and OS of AT13387 administered alone or in combination with crizotinib
time frame: 18 months
description: Number of patients with adverse events
PFS and OS as measured in weeks
arm group label: AT13387 and Crizotinib
arm group type: Experimental
description: Part A is a single-arm, Phase 1, open-label, dose-escalation design in patients with NSCLC who have already been receiving crizotinib 250 mg by mouth (PO) twice daily (BID) for at least 8 weeks and are still tolerating treatment at that dose. Patients will continue treatment with crizotinib + escalating doses of AT13387 IV weekly for 3 weeks in a 4-week cycle. Each cohort will consist of at least 6 patients until the maximum tolerated dose (MTD) is reached. An additional 12 patients will be treated at the MTD level of AT13387 in combination with crizotinib to confirm the safety profile of the combination at that dose level.
arm group label: Crizotinib versus crizotinib + AT13387
arm group type: Active Comparator
description: Part B is a Phase 2, open-label, randomized continuation design comparing crizotinib alone versus the combination of crizotinib + AT13387 at the MTD established in Part A. Part B will enroll 128 patients with NSCLC who have been treated with crizotinib for at least 8 weeks and are still tolerating treatment without evidence of disease progression.
arm group label: AT13387 or AT13387 + crizotinib
arm group type: Active Comparator
description: Part C is an open-label, randomized, Phase 2, Simon's 2-stage design of AT13387 administered alone once weekly for 3 weeks (QW×3) or in combination with crizotinib at the MTD established in Part A.
intervention type: Drug
intervention name: AT13387
description: HSP90 inhibitor
arm group label: AT13387 and Crizotinib
arm group label: AT13387 or AT13387 + crizotinib
arm group label: Crizotinib versus crizotinib + AT13387
intervention type: Drug
intervention name: Crizotinib
description: ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor
arm group label: AT13387 and Crizotinib
arm group label: AT13387 or AT13387 + crizotinib
arm group label: Crizotinib versus crizotinib + AT13387
other name: Xalkori
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean-Charles Soria, MD
role: Principal Investigator
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: France
country: Korea, Republic of
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Crizotinib