<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/NCT03838692</url>
  </required_header>
  <id_info>
    <org_study_id>AAAR5196</org_study_id>
    <nct_id>NCT03838692</nct_id>
  </id_info>
  <brief_title>Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer</brief_title>
  <official_title>A Study of Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer (MTC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Antonio Fojo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Millennium Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to determine in an exploratory manner the objective&#xD;
      overall response rate to ponatinib in the treatment of patients with advanced or metastatic&#xD;
      MTC previously treated with cabozantinib or vandetanib who have tumors with&#xD;
      rearranged-during-transfection (RET) mutations and have tumors without RET mutations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ponatinib is an investigational agent that blocks abnormal cancer proteins and therefore&#xD;
      harms cancer cells. It was recently approved by the Food and Drug Administration for leukemia&#xD;
      treatment, but is not approved for medullary thyroid cancer treatment. Early studies,&#xD;
      however, have shown that medullary thyroid tumors respond to ponatinib. These studies were&#xD;
      done in the laboratory and not performed on humans. This is a study designed for patients&#xD;
      with medullary thyroid cancer. Treatment will consist of a drug called ponatinib which is a&#xD;
      pill that taken once each day and continue throughout the duration of the study. The purpose&#xD;
      of the study is to:&#xD;
&#xD;
        1. Determine if this treatment will be effective in decreasing the amount of cancer and, if&#xD;
           it does, to determine how long the response will last.&#xD;
&#xD;
        2. Determine the side effects that may occur with this treatment.&#xD;
&#xD;
        3. To analyze genetic mutations in tumors to help us understand how tumors grow and how&#xD;
           these drugs interact with the mechanisms within the tumor.&#xD;
&#xD;
      Ponatinib has been given to many patients with leukemia and is now approved by the United&#xD;
      States Food and Drug Administration for treatment of certain types of leukemia. This study&#xD;
      will seek to determine if ponatinib can bring benefit to patients with medullary thyroid&#xD;
      cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Closed by sponsor&#xD;
  </why_stopped>
  <start_date type="Actual">July 26, 2019</start_date>
  <completion_date type="Actual">June 14, 2021</completion_date>
  <primary_completion_date type="Actual">June 14, 2021</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>Objective Response Rate (ORR)</measure>
    <time_frame>24 months</time_frame>
    <description>ORR is defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR). Responses are based on assessments per RECIST.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>24 months</time_frame>
    <description>PFS is defined as the time from the first day of trial treatment to the first documented disease progression per the Kaplan-Meier curve.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Total Number of Adverse Reactions</measure>
    <time_frame>24 months</time_frame>
    <description>Testing safety and toxicity assessed using CTCAE criteria</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Medullary Thyroid Cancer</condition>
  <arm_group>
    <arm_group_label>Ponatinib Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ponatinib tablets will be taken by mouth, continuously, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment can be taken with water, with or without food, at approximately the same time each day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ponatinib</intervention_name>
    <description>A daily oral dose at 30 mg.</description>
    <arm_group_label>Ponatinib Arm</arm_group_label>
    <other_name>ICLUSIG</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of localized or metastatic unresectable MTC.&#xD;
&#xD;
          -  Measurable disease, defined as at least one lesion that can be accurately measured in&#xD;
             at least one dimension (longest diameter to be recorded for non-nodal lesions and&#xD;
             short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with&#xD;
             spiral computerized tomography (CT) scan.&#xD;
&#xD;
          -  The last dose of previous therapy targeting RET kinase must be given at least 4 weeks&#xD;
             - Previous treatment with cytotoxic chemotherapy, immunotherapy, or radiotherapy are&#xD;
             permitted, if the last dose was given at least 4 weeks prior to the first dose of&#xD;
             ponatinib&#xD;
&#xD;
          -  Patient must have failed (progressed on or been intolerant of) prior treatment with&#xD;
             cabozantinib or vandetanib.&#xD;
&#xD;
          -  Age ≥18 years old&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤2&#xD;
&#xD;
          -  Normal organ and marrow function as defined below:&#xD;
&#xD;
          -  Negative pregnancy test for women of childbearing potential or male patients, even if&#xD;
             surgically sterilized (i.e., status post-vasectomy), who:&#xD;
&#xD;
               -  Agree to practice effective barrier contraception during the entire study&#xD;
                  treatment period and through 4 months after the last dose of study drug, or&#xD;
&#xD;
               -  Agree to completely abstain from heterosexual intercourse&#xD;
&#xD;
          -  Normal QT interval corrected on screening electrocardiogram (ECG) evaluation, defined&#xD;
             as the corrected QT interval by Fredericia (QTcF) of ≤450 ms.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
             and follow the guidelines of the clinical protocol including visits for treatment and&#xD;
             follow up&#xD;
&#xD;
          -  Life expectancy of greater than 12 weeks&#xD;
&#xD;
          -  Available archival tissue or willingness to undergo fresh biopsy if no archival tissue&#xD;
             is available.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are receiving any other investigational agent.&#xD;
&#xD;
          -  Patients with brain metastases or spinal cord compression unless they completed&#xD;
             radiation therapy ≥4 weeks prior to the first dose of ponatinib and are stable without&#xD;
             steroids or anti-convulsant therapy for ≥10 days.&#xD;
&#xD;
          -  Patients who cannot discontinue medications that are known to be associated with&#xD;
             Torsades de Pointes. These medications are listed in Attachment 3&#xD;
&#xD;
          -  Uncontrolled hypertension (systolic blood pressure &gt;150 or diastolic blood pressure&#xD;
             &gt;100&#xD;
&#xD;
          -  Significant or active cardiovascular disease within 6 months prior to enrollment&#xD;
&#xD;
          -  A history of pancreatitis or alcohol abuse&#xD;
&#xD;
          -  Uncontrolled hypertriglyceridemia (&gt;450 mg/dL)&#xD;
&#xD;
          -  Major surgery (with the exception of minor surgical procedures, such as catheter&#xD;
             placement or tumor biopsy) within 28 days prior to the first dose of ponatinib&#xD;
&#xD;
          -  Ongoing or active infection including known history of human immunodeficiency virus&#xD;
             (HIV), hepatitis B virus (HBV), or hepatitis C (HCV). Testing for these viruses is not&#xD;
             required in the absence of a history of infection.&#xD;
&#xD;
          -  Suffer from any condition or illness that, in the opinion of the investigator, would&#xD;
             compromise patient safety or interfere with the evaluation of the safety of the study&#xD;
             drug&#xD;
&#xD;
          -  Evidence of a bleeding diathesis that cannot be corrected with standard therapy or&#xD;
             factor replacement&#xD;
&#xD;
          -  Presence of another primary malignancy within the past 2 years (except for&#xD;
             non-melanoma skin cancer or cervical cancer in situ. Prior prostate cancer is also&#xD;
             permitted if prostate-specific antigen (PSA) is now undetectable)&#xD;
&#xD;
          -  Pregnant or lactating&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to investigational agent&#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>Antonio Fojo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>February 11, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>October 6, 2021</last_update_submitted>
  <last_update_submitted_qc>October 6, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>Antonio Fojo</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine at the Columbia University Medical</investigator_title>
  </responsible_party>
  <keyword>Ponatinib</keyword>
  <keyword>Metastatic Medullary</keyword>
  <keyword>Advanced Medullary</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thyroid Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Neuroendocrine</mesh_term>
    <mesh_term>Thyroid Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ponatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03838692
org study id: AAAR5196
nct id: NCT03838692
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of this study is to determine in an exploratory manner the objective
      overall response rate to ponatinib in the treatment of patients with advanced or metastatic
      MTC previously treated with cabozantinib or vandetanib who have tumors with
      rearranged-during-transfection (RET) mutations and have tumors without RET mutations.
Ponatinib is an investigational agent that blocks abnormal cancer proteins and therefore
      harms cancer cells. It was recently approved by the Food and Drug Administration for leukemia
      treatment, but is not approved for medullary thyroid cancer treatment. Early studies,
      however, have shown that medullary thyroid tumors respond to ponatinib. These studies were
      done in the laboratory and not performed on humans. This is a study designed for patients
      with medullary thyroid cancer. Treatment will consist of a drug called ponatinib which is a
      pill that taken once each day and continue throughout the duration of the study. The purpose
      of the study is to:

        1. Determine if this treatment will be effective in decreasing the amount of cancer and, if
           it does, to determine how long the response will last.

        2. Determine the side effects that may occur with this treatment.

        3. To analyze genetic mutations in tumors to help us understand how tumors grow and how
           these drugs interact with the mechanisms within the tumor.

      Ponatinib has been given to many patients with leukemia and is now approved by the United
      States Food and Drug Administration for treatment of certain types of leukemia. This study
      will seek to determine if ponatinib can bring benefit to patients with medullary thyroid
      cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: 24 months
description: ORR is defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR). Responses are based on assessments per RECIST.
measure: Progression-Free Survival (PFS)
time frame: 24 months
description: PFS is defined as the time from the first day of trial treatment to the first documented disease progression per the Kaplan-Meier curve.
measure: Total Number of Adverse Reactions
time frame: 24 months
description: Testing safety and toxicity assessed using CTCAE criteria
arm group label: Ponatinib Arm
arm group type: Experimental
description: Ponatinib tablets will be taken by mouth, continuously, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment can be taken with water, with or without food, at approximately the same time each day.
intervention type: Drug
intervention name: Ponatinib
description: A daily oral dose at 30 mg.
arm group label: Ponatinib Arm
other name: ICLUSIG
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Antonio Fojo, MD
role: Principal Investigator
affiliation: Columbia University
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Columbia University
investigator full name: Antonio Fojo
investigator title: Assistant Professor of Medicine at the Columbia University Medical
mesh term: Thyroid Neoplasms
mesh term: Carcinoma, Neuroendocrine
mesh term: Thyroid Diseases
mesh term: Ponatinib
sharing ipd: No