<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/NCT03292536</url>
  </required_header>
  <id_info>
    <org_study_id>HCI103657</org_study_id>
    <nct_id>NCT03292536</nct_id>
  </id_info>
  <brief_title>Merestinib on Bone Metastases in Subjects With Breast Cancer</brief_title>
  <official_title>An Exploratory Phase 1B Study to Assess the Effects of Merestinib on Bone Metastases in Subjects With Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Utah</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>
      This is an open label, pharmacodynamics, intrapatient dose escalation phase 1B study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Enrollment incomplete by the end of the contracted enrollment period&#xD;
  </why_stopped>
  <start_date type="Actual">January 11, 2018</start_date>
  <completion_date type="Actual">June 24, 2019</completion_date>
  <primary_completion_date type="Actual">June 24, 2019</primary_completion_date>
  <phase>Phase 1</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>
    <intervention_model_description>a single arm, open label, pharmacodynamics, intrapatient dose escalation phase 1B study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events that Occur</measure>
    <time_frame>12 weeks, checked at every visit in that time period</time_frame>
    <description>To assess the tolerability of merestinib in combination with standard breast cancer therapies.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in urinary N-telopeptide level</measure>
    <time_frame>12 weeks</time_frame>
    <description>To measure the change in urinary N-telopeptide level after 12 weeks of therapy with merestinib</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Absolute and percentage change in serum B-CTX, TRAP-5b, P1NP and BSAP</measure>
    <time_frame>12 weeks</time_frame>
    <description>To measure the absolute and percentage change in serum β-CTX, TRAP-5b, P1NP, and BSAP at time points from baseline to 12 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to skeletal-related events</measure>
    <time_frame>12 weeks</time_frame>
    <description>To evaluate determine time to skeletal-related event(s) following initiation of merestinib dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in pain scores</measure>
    <time_frame>12 weeks</time_frame>
    <description>To evaluate change in pain as measured by pain scores during and after 12 weeks of merestinib treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in pain by narcotic use</measure>
    <time_frame>12 weeks</time_frame>
    <description>To evaluate change in pain as measured by narcotic use) during and after 12 weeks of merestinib treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in bone lesion uptake</measure>
    <time_frame>12 weeks</time_frame>
    <description>To evaluate the change in bone lesion uptake on NaF PET scan after 12 weeks of merestinib treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Bone Metastases</condition>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Merestinib, all patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Merestinib</intervention_name>
    <description>*The merestinib does escalation timing will depend on the schedule of the other anticancer regimen*&#xD;
Subjects will receive merestinib 40mg PO Qday (dose level 1) for 2 to 4 weeks followed by 80mg PO daily (dose level 2) for 4 to 10 weeks</description>
    <arm_group_label>Merestinib, all patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At least 1 bone metastases must be present&#xD;
&#xD;
          -  Urinary N-telopeptide level above 20nM BCE/mM creatinine measured at ARUP&#xD;
&#xD;
          -  Archived or freshly biopsied primary and/or bone metastatic tumor tissue available in&#xD;
             paraffin-embedded blocks or slides that is expected to yield 9 slides&#xD;
&#xD;
          -  Life expectancy of ≥ 6 months&#xD;
&#xD;
          -  Toxicity related to prior treatments must either have resolved to grade 1 or less,&#xD;
             returned to baseline, or be deemed irreversible&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (within 28 days&#xD;
             prior to enrollment)&#xD;
&#xD;
          -  Planning to remain on current breast cancer therapy for at least 12 weeks.&#xD;
&#xD;
          -  At least one prior line of therapy for metastatic breast cancer&#xD;
&#xD;
          -  Concurrent treatment with bisphosphonates or denosumab is required.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to swallow or take anything orally&#xD;
&#xD;
          -  ECG abnormalities:&#xD;
&#xD;
               -  Prolonged QTcF (Fredericia's correction) interval on screening ECG (≥ 450 msec)&#xD;
&#xD;
               -  QRS ˃ 120 msec&#xD;
&#xD;
               -  PR ˃ 210 msec&#xD;
&#xD;
               -  Any prior history, or current evidence of second- or third-degree heart block&#xD;
&#xD;
               -  Heart rate ˂ 40 beats per minute at screening&#xD;
&#xD;
               -  ECG second degree heart block (Mobitz's Type 2 or Wenckebach)&#xD;
&#xD;
               -  Complete heart block&#xD;
&#xD;
               -  Left bundle branch block or bifascicular block (right bundle branch block and&#xD;
                  left anterior hemiblock together)&#xD;
&#xD;
               -  Episodes of ventricular tachycardia&#xD;
&#xD;
          -  Any known prior malignancy (not including non-melanoma skin cancers), unless treated&#xD;
             with curative intent&#xD;
&#xD;
          -  A serious uncontrolled medical disorder or active infection, which would impair the&#xD;
             ability of the subject to receive protocol therapy&#xD;
&#xD;
          -  Current or recent (within 3 months) gastrointestinal disease that could impact the&#xD;
             absorption (i.e., unmanageable diarrhea or malabsorption at the time of screening)&#xD;
&#xD;
          -  Inadequate bone marrow function defined as:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ˂ 1,500 cells/mm3&#xD;
&#xD;
               -  Platelet count ˂ 100,000 cells/mm3&#xD;
&#xD;
               -  Hemoglobin ˂ 9 g/dL&#xD;
&#xD;
          -  Inadequate hepatic function defined as:&#xD;
&#xD;
               -  Total bilirubin ˃ 1.5 x institutional upper limit of normal (IULN) (Unless due to&#xD;
                  diagnosis of Gilbert's Syndrome)&#xD;
&#xD;
               -  Alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) ˃ 2.5 x&#xD;
                  IULN&#xD;
&#xD;
          -  Inadequate renal function defined as: Serum creatinine ˃ 1.5 x ULN&#xD;
&#xD;
          -  Prothrombin time (PT)/partial thromboplastin time (PTT) ˃ 1.5 times the ULN&#xD;
&#xD;
          -  Serum sodium, potassium, and calcium levels not within normal limits.&#xD;
&#xD;
          -  Any atrophic macular condition including intermediate or advanced age-related macular&#xD;
             degeneration&#xD;
&#xD;
          -  Patients receiving medications that are known to be substrates of CYP2C8 (including&#xD;
             paclitaxel), CYP2C9, or CYP2C19 or to be oral substrates of CYP3A with narrow&#xD;
             therapeutic window (listed on http://medicine.iupui.edu/clinpharm/ddis/main-table).&#xD;
             Subjects who have discontinued any of these medications must have a wash-out period of&#xD;
             at least 5 days or 5 half-lives of the drug (whichever is longer) prior to the first&#xD;
             dose of merestinib&#xD;
&#xD;
          -  Exposure to any investigational drug or placebo within 4 weeks of enrollment&#xD;
&#xD;
          -  Any other sound medical, psychiatric, and/or social reasons as determined by the&#xD;
             investigator&#xD;
&#xD;
          -  History of diseases with influence on bone metabolism, such as Paget's disease,&#xD;
             osteogenesis imperfecta, active primary or secondary hyperparathyroidism, and primary&#xD;
             or secondary hyperthyroidism within 12 months prior to study entry&#xD;
&#xD;
          -  Patients with known symptomatic brain metastasis. Subjects with controlled brain&#xD;
             metastasis (no radiographic progression at least 4 weeks following radiation and/or&#xD;
             surgical treatment and no neurological signs or symptoms) will be allowed&#xD;
&#xD;
          -  History of allergy to merestinib or chemically related compounds&#xD;
&#xD;
          -  History of osteonecrosis of the jaw&#xD;
&#xD;
          -  Change in chemotherapy or hormone therapy within 8 weeks of the start of the study.&#xD;
&#xD;
          -  Active gout or inflammatory arthritis requiring treatment&#xD;
&#xD;
          -  Use within 28 days of registration of calcitonin, recombinant parathyroid&#xD;
             hormone-related peptides, mithramycin, radium, strontium ranelate, or gallium nitrate.&#xD;
&#xD;
          -  Adult patients who require monitored anesthesia for PET scanning due to&#xD;
             claustrophobia.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>January 7, 2021</last_update_submitted>
  <last_update_submitted_qc>January 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 8, 2021</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>Breast Neoplasms</mesh_term>
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Bone Neoplasms</mesh_term>
    <mesh_term>Bone Marrow Diseases</mesh_term>
  </condition_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/NCT03292536
org study id: HCI103657
nct id: NCT03292536
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is an open label, pharmacodynamics, intrapatient dose escalation phase 1B study.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: a single arm, open label, pharmacodynamics, intrapatient dose escalation phase 1B study
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events that Occur
time frame: 12 weeks, checked at every visit in that time period
description: To assess the tolerability of merestinib in combination with standard breast cancer therapies.
measure: Change in urinary N-telopeptide level
time frame: 12 weeks
description: To measure the change in urinary N-telopeptide level after 12 weeks of therapy with merestinib
measure: Absolute and percentage change in serum B-CTX, TRAP-5b, P1NP and BSAP
time frame: 12 weeks
description: To measure the absolute and percentage change in serum β-CTX, TRAP-5b, P1NP, and BSAP at time points from baseline to 12 weeks.
measure: Time to skeletal-related events
time frame: 12 weeks
description: To evaluate determine time to skeletal-related event(s) following initiation of merestinib dosing
measure: Change in pain scores
time frame: 12 weeks
description: To evaluate change in pain as measured by pain scores during and after 12 weeks of merestinib treatment
measure: Change in pain by narcotic use
time frame: 12 weeks
description: To evaluate change in pain as measured by narcotic use) during and after 12 weeks of merestinib treatment
measure: Change in bone lesion uptake
time frame: 12 weeks
description: To evaluate the change in bone lesion uptake on NaF PET scan after 12 weeks of merestinib treatment
arm group label: Merestinib, all patients
arm group type: Experimental
intervention type: Drug
intervention name: Merestinib
description: *The merestinib does escalation timing will depend on the schedule of the other anticancer regimen*
Subjects will receive merestinib 40mg PO Qday (dose level 1) for 2 to 4 weeks followed by 80mg PO daily (dose level 2) for 4 to 10 weeks
arm group label: Merestinib, all patients
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Neoplasm Metastasis
mesh term: Bone Neoplasms
mesh term: Bone Marrow Diseases
sharing ipd: No