<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/NCT02244463</url>
  </required_header>
  <id_info>
    <org_study_id>14-223</org_study_id>
    <nct_id>NCT02244463</nct_id>
  </id_info>
  <brief_title>A Phase II Study of MLN0128 in Metastatic Anaplastic Thyroid Cancer</brief_title>
  <official_title>A Phase II Study of MLN0128 in Metastatic Anaplastic Thyroid Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Millennium Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study is studying a targeted therapy (ML0N128) as a possible treatment for&#xD;
      anaplastic thyroid cancer.&#xD;
&#xD;
      This research study is a Phase II clinical trial. Phase II clinical trials test the safety&#xD;
      and effectiveness of an investigational intervention to learn whether the intervention works&#xD;
      in treating a specific disease. &quot;Investigational&quot; means that the intervention is being&#xD;
      studied. The FDA (the U.S. Food and Drug Administration) has not approved MLN0128 as a&#xD;
      treatment for any disease.&#xD;
&#xD;
      MLN0128 prevents tumor cells from dividing and growing by selectively and potently inhibiting&#xD;
      a chemical, mTOR kinase, which regulates cell growth and survival. Patients with anaplastic&#xD;
      thyroid cancer have been observed to sometimes carry genetic alterations in their tumor cells&#xD;
      which may make the cancer more sensitive to inhibition by MLN0128.&#xD;
&#xD;
      In this research study,the investigators are investigating usefulness of MLN0128 in&#xD;
      metastatic anaplastic thyroid cancer cases.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients who fulfill eligibility criteria will be entered into the trial to receive ML0N128.&#xD;
      The participant will be given a study drug-dosing diary for each treatment cycle. After the&#xD;
      screening procedures confirm participation in the research study.&#xD;
&#xD;
      - MLN0128 - Fixed doses daily per treatment cycle&#xD;
&#xD;
      The treatment cycles will continue until the participants disease gets worse or is taken off&#xD;
      treatment for any other reason.Once treatment has been discontinued the investigators will&#xD;
      check on the participants health status by phone for the rest of their life.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 2015</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>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>Progression Free Survival</measure>
    <time_frame>baseline, 4 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall All Response Rate</measure>
    <time_frame>2 Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival Rate</measure>
    <time_frame>2 Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Serious and Non-Serious Adverse Events</measure>
    <time_frame>2 Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Identification of biomarkers predictive of response to therapy with MLN0128</measure>
    <time_frame>2 Years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Anaplastic Thyroid Cancer</condition>
  <condition>Thyroid Cancer</condition>
  <arm_group>
    <arm_group_label>MLN0128</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment will be administered on an outpatient basis. MLN0128 at fixed dose will be administered orally, daily for treatment cycle. The participant will be requested to maintain a medication diary of medication. The medication diary will be returned to clinic staff at the end of each cycle. Treatment with MLN0128 will continue until progression or withdrawal of consent.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MLN0128</intervention_name>
    <description>This is a non-randomized phase II study to investigate efficacy of MLN0128 in metastatic anaplastic thyroid cancer cases.</description>
    <arm_group_label>MLN0128</arm_group_label>
    <other_name>INK128</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients 18 years or older&#xD;
&#xD;
          -  Any number of prior chemotherapy or targeted agents including rapamycin analogues&#xD;
             allowed&#xD;
&#xD;
          -  Newly diagnosed or refractory/metastatic anaplastic thyroid cancer confirmed by&#xD;
             histology, incurable by surgery, radiotherapy or chemoradiotherapy alone or in&#xD;
             combination&#xD;
&#xD;
          -  Must have measurable disease&#xD;
&#xD;
          -  ECOG performance status 0-2&#xD;
&#xD;
          -  No active intracranial metastases&#xD;
&#xD;
          -  Tissue for correlative studies must be available&#xD;
&#xD;
          -  Ability to swallow oral medications&#xD;
&#xD;
          -  Voluntary written consent must be given before performance of any study related&#xD;
             procedure&#xD;
&#xD;
          -  Adequate organ function, as specified below, within 21 days:&#xD;
&#xD;
               -  Bone marrow reserve consistent with: absolute neutrophil count (ANC) ≥ 1.5 x&#xD;
                  109/L; platelet count ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL;&#xD;
&#xD;
               -  Hepatic: total bilirubin ≤1.5 x upper limit of normal (ULN), transaminases&#xD;
                  (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and&#xD;
                  alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) ≤2.5 x ULN&#xD;
                  (≤5 x ULN if liver metastases are present);&#xD;
&#xD;
               -  Renal: creatinine clearance ≥50 mL/min&#xD;
&#xD;
               -  Metabolic: fasting serum glucose (≤ 130 mg/dL) and fasting triglycerides ≤ 300&#xD;
                  mg/dL&#xD;
&#xD;
               -  Left ventricular ejection fraction (LVEF) within 5 absolute percentage points of&#xD;
                  institutional standard of normal as measured by echocardiogram (ECHO) or multiple&#xD;
                  gated acquisition scan (MUGA) within 4 weeks prior to first study drug&#xD;
                  administration (ie, if the institutional normal is 50%, subject's LVEF may be as&#xD;
                  low as 45% to be eligible for the study)&#xD;
&#xD;
          -  Female patients who:&#xD;
&#xD;
               -  Are postmenopausal for at least 1 year before the screening visit, OR&#xD;
&#xD;
               -  Are surgically sterile, OR&#xD;
&#xD;
               -  If they are of childbearing potential, agree to practice 2 effective methods of&#xD;
                  contraception, at the same time, from the time of signing the informed consent&#xD;
                  through 90 days after the last dose of study drug, or agree to completely abstain&#xD;
                  from heterosexual intercourse&#xD;
&#xD;
          -  Male patients, even if surgically sterilized (ie, status post-vasectomy), who:&#xD;
&#xD;
               -  Agree to practice effective barrier contraception during the entire study&#xD;
                  treatment period and through 90 days after the last dose of study drug, or&#xD;
&#xD;
               -  Agree to completely abstain from heterosexual intercourse&#xD;
&#xD;
          -  Treatment with strong CYP2C19, CYP3A4, and CYP2C9 inhibitors and/or inducers must be&#xD;
             discontinued&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female patients who are both lactating and breastfeeding or have a positive serum&#xD;
             pregnancy test during the screening period&#xD;
&#xD;
          -  Any serious medical or psychiatric illness that could, in the investigator's opinion,&#xD;
             potentially interfere with the completion of treatment&#xD;
&#xD;
          -  Treatment with any investigational products within 14 days&#xD;
&#xD;
          -  Failed to recover from the reversible effects of prior anticancer therapies&#xD;
&#xD;
          -  Manifestations of malabsorption due to prior gastrointestinal surgery or disease&#xD;
&#xD;
          -  Poorly controlled diabetes mellitus&#xD;
&#xD;
          -  History of any of the following within the last 6 months prior to study entry:&#xD;
&#xD;
               -  Ischemic myocardial event&#xD;
&#xD;
               -  Ischemic cerebrovascular event&#xD;
&#xD;
               -  Requirement for inotropic support (excluding digoxin) or serious (uncontrolled)&#xD;
                  cardiac arrhythmia&#xD;
&#xD;
               -  Placement of a pacemaker for control of rhythm&#xD;
&#xD;
               -  New York Heart Association Class III or IV heart failure&#xD;
&#xD;
               -  Pulmonary embolism&#xD;
&#xD;
          -  Significant active cardiovascular or pulmonary disease at the time of study entry,&#xD;
             including:&#xD;
&#xD;
               -  Uncontrolled high blood pressure&#xD;
&#xD;
               -  Pulmonary hypertension&#xD;
&#xD;
               -  Uncontrolled asthma or O2 saturation &lt; 90%&#xD;
&#xD;
               -  Significant valvular disease&#xD;
&#xD;
               -  Medically significant (symptomatic) bradycardia&#xD;
&#xD;
               -  History of arrhythmia requiring an implantable cardiac defibrillator&#xD;
&#xD;
               -  Baseline prolongation of the rate-corrected QT interval (QTc)&#xD;
&#xD;
          -  Treatment with hematopoietic growth factors, transfusions of blood and blood products,&#xD;
             or systemic corticosteroids&#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>Kartik Seghal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hoag Memorial Hospital Presbyterian</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Medical School</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <last_update_submitted>February 18, 2022</last_update_submitted>
  <last_update_submitted_qc>February 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Kartik Sehgal</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Anaplastic Thyroid Cancer</keyword>
  <keyword>Thyroid Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thyroid Neoplasms</mesh_term>
    <mesh_term>Thyroid Carcinoma, Anaplastic</mesh_term>
    <mesh_term>Thyroid Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There are no plans to share individual participant data. Cumulative results will be posted here and published.</ipd_description>
  </patient_data>
  <pending_results>
    <submitted>April 6, 2023</submitted>
    <returned>April 28, 2023</returned>
    <submitted>August 21, 2023</submitted>
    <returned>September 13, 2023</returned>
  </pending_results>
  <!-- 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/NCT02244463
org study id: 14-223
nct id: NCT02244463
lead sponsor: 
collaborator: 
has dmc: Yes
This research study is studying a targeted therapy (ML0N128) as a possible treatment for
      anaplastic thyroid cancer.

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational intervention to learn whether the intervention works
      in treating a specific disease. "Investigational" means that the intervention is being
      studied. The FDA (the U.S. Food and Drug Administration) has not approved MLN0128 as a
      treatment for any disease.

      MLN0128 prevents tumor cells from dividing and growing by selectively and potently inhibiting
      a chemical, mTOR kinase, which regulates cell growth and survival. Patients with anaplastic
      thyroid cancer have been observed to sometimes carry genetic alterations in their tumor cells
      which may make the cancer more sensitive to inhibition by MLN0128.

      In this research study,the investigators are investigating usefulness of MLN0128 in
      metastatic anaplastic thyroid cancer cases.
Patients who fulfill eligibility criteria will be entered into the trial to receive ML0N128.
      The participant will be given a study drug-dosing diary for each treatment cycle. After the
      screening procedures confirm participation in the research study.

      - MLN0128 - Fixed doses daily per treatment cycle

      The treatment cycles will continue until the participants disease gets worse or is taken off
      treatment for any other reason.Once treatment has been discontinued the investigators will
      check on the participants health status by phone for the rest of their life.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival
time frame: baseline, 4 months
measure: Overall All Response Rate
time frame: 2 Years
measure: Overall Survival Rate
time frame: 2 Years
measure: Number of Participants with Serious and Non-Serious Adverse Events
time frame: 2 Years
measure: • Identification of biomarkers predictive of response to therapy with MLN0128
time frame: 2 Years
arm group label: MLN0128
arm group type: Experimental
description: Treatment will be administered on an outpatient basis. MLN0128 at fixed dose will be administered orally, daily for treatment cycle. The participant will be requested to maintain a medication diary of medication. The medication diary will be returned to clinic staff at the end of each cycle. Treatment with MLN0128 will continue until progression or withdrawal of consent.
intervention type: Drug
intervention name: MLN0128
description: This is a non-randomized phase II study to investigate efficacy of MLN0128 in metastatic anaplastic thyroid cancer cases.
arm group label: MLN0128
other name: INK128
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kartik Seghal, MD
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Kartik Sehgal
investigator title: Principal Investigator
mesh term: Thyroid Neoplasms
mesh term: Thyroid Carcinoma, Anaplastic
mesh term: Thyroid Diseases
sharing ipd: No
ipd description: There are no plans to share individual participant data. Cumulative results will be posted here and published.
submitted: April 6, 2023
returned: April 28, 2023
submitted: August 21, 2023
returned: September 13, 2023