<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/NCT03042819</url>
  </required_header>
  <id_info>
    <org_study_id>SAR-002</org_study_id>
    <nct_id>NCT03042819</nct_id>
  </id_info>
  <brief_title>Study of Selinexor and Doxorubicin in Advanced Soft Tissue Sarcomas</brief_title>
  <official_title>A Phase 1b Trial of Selinexor Plus Doxorubicin in Advanced Soft Tissue Sarcomas (STS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Karyopharm Therapeutics Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 1b study of investigational drug selinexor in combination with doxorubicin in&#xD;
      patients with locally advanced or metastatic soft tissue sarcoma. The purpose of this study&#xD;
      is to determine how safe and tolerable the combination is, as well as the best dose of the&#xD;
      study drugs in this patient population.&#xD;
&#xD;
      Selinexor (also called KPT-330), works by trapping &quot;tumor suppressor proteins&quot; within the&#xD;
      cell and thus causing the cancer cells to die or stop growing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 1b study of investigational drug selinexor in combination with doxorubicin in&#xD;
      patients with locally advanced or metastatic soft tissue sarcoma.&#xD;
&#xD;
      Patients will be screened for eligibility within 28 days of the start of the study drugs. In&#xD;
      addition to standard tests and procedures, research tumor tissue (archival or fresh biopsy)&#xD;
      will be collected for collection for pharmacodynamics. Participants will also be asked if&#xD;
      they agree to optional biopsies at 6 cycles if their cancer is responding and at disease&#xD;
      progression.&#xD;
&#xD;
      Eligible participants will then receive the study drugs in 21 day cycles. Selinexor will be&#xD;
      given by mouth and doxorubicin will be given by vein, once a week, for 6 cycles.&#xD;
&#xD;
      Participants will be restaged every 2 cycles. If participants respond to treatment after 6&#xD;
      cycles, they may be able to continue the selinexor alone as a maintenance treatment until&#xD;
      progression or unacceptable toxicity.&#xD;
&#xD;
      While receiving the study drug, many of the screening tests will be repeated. Additional&#xD;
      tests and procedures include blood sample collection for pharmacokinetics and&#xD;
      pharmacodynamics.&#xD;
&#xD;
      When participants stop the study drug permanently for any reason, an end of treatment visit,&#xD;
      28-day follow-up, and long term follow up every 90 days will occur.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 16, 2017</start_date>
  <completion_date type="Actual">June 30, 2021</completion_date>
  <primary_completion_date type="Actual">November 30, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate the Incidence of Treatment-Emergent Adverse Events, graded and categorized according to the CTCAE v4.0.</measure>
    <time_frame>3 years</time_frame>
    <description>All adverse events will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution. SAE specific incidence and exact 95% confidence interval will be provided where appropriate.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the recommended phase II dose (RP2D) of Selinexor in combination with doxorubicin</measure>
    <time_frame>3 years</time_frame>
    <description>The RP2D will be determined according to interim mTPI monitoring algorithm (Figure 5.1) using the dose determining set.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of Grade 3 Toxicities</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response Rate</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival Rate</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Soft Tissue Sarcoma</condition>
  <arm_group>
    <arm_group_label>Selinexor plus Doxorubicin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Selinexor will be given by mouth (orally) once a week:&#xD;
Dose Level -1 = 40 mg Dose Level 1 (Starting Dose) = 60 mg Dose Level 2 = 80 mg&#xD;
Doxorubicin will be given by vein (intravenously) at a dose of 75 mg/m2 once every 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Selinexor</intervention_name>
    <description>Selinexor is a Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1), thereby forcing the nuclear retention of key tumor suppressor proteins (TSPs).</description>
    <arm_group_label>Selinexor plus Doxorubicin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin</intervention_name>
    <description>Doxorubicin is currently approved for various cancers. Doxorubicin inhibits DNA synthesis and repair by inhibiting topoisomerase II and also by intercalation between base pairs on the DNA helix. These actions result in the blockade of DNA and RNA synthesis and fragmentation of DNA.</description>
    <arm_group_label>Selinexor plus Doxorubicin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Patient must be willing and able to comply with scheduled visits, treatment plan,&#xD;
             laboratory tests and other study procedures.&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Patients must have histologically confirmed locally advanced/unresectable or&#xD;
             metastatic soft tissue sarcoma.&#xD;
&#xD;
          -  Patients must have not received prior doxorubicin.&#xD;
&#xD;
          -  Patient must show evidence of progressive disease on study entry or newly diagnosed&#xD;
             patients with de novo metastatic measurable disease&#xD;
&#xD;
          -  Patient must have measureable disease as defined by RECIST 1.1.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1&#xD;
&#xD;
          -  Adequate hematopoietic function&#xD;
&#xD;
          -  Adequate hepatic function:&#xD;
&#xD;
          -  Adequate renal function&#xD;
&#xD;
          -  Adequate cardiac function13&#xD;
&#xD;
          -  Patients must agree to use methods of contraception as a agreed upon by the patient&#xD;
             and study doctor&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient is pregnant or lactating&#xD;
&#xD;
          -  Radiation, chemotherapy, immunotherapy, any other systemic anticancer therapy, or&#xD;
             participation in an investigational anti-cancer study ≤3 weeks prior to initiation of&#xD;
             therapy.&#xD;
&#xD;
          -  Major surgery within 4 weeks before initiation of therapy&#xD;
&#xD;
          -  Unstable cardiovascular function&#xD;
&#xD;
          -  Active, ongoing or uncontrolled active infection within one week prior to first dose.&#xD;
&#xD;
          -  Malignancies other than disease under study within 2 years prior to Cycle 1, Day 1.&#xD;
&#xD;
          -  Known to be HIV seropositive&#xD;
&#xD;
          -  Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C&#xD;
             virus (HCV) RNA or hepatitis B virus (HBV) surface antigen (HBsAg)&#xD;
&#xD;
          -  Patients with active CNS malignancy.&#xD;
&#xD;
          -  Patients with any gastrointestinal dysfunctions that could interfere with the&#xD;
             absorption of Selinexor or patients with significantly diseased or obstructed&#xD;
             gastrointestinal tract or uncontrolled vomiting or diarrhea.&#xD;
&#xD;
          -  Inability or unwillingness to take supportive medications such as anti-nausea and anti&#xD;
             anorexia agents.&#xD;
&#xD;
          -  In the opinion of the Investigator, patients who are significantly below their ideal&#xD;
             body weight&#xD;
&#xD;
          -  Serious psychiatric or medical conditions that could interfere with treatment&#xD;
&#xD;
          -  Concurrent therapy with approved or investigational anticancer therapeutic agents&#xD;
&#xD;
          -  Any condition that, in the opinion of the Investigator, would interfere with&#xD;
             evaluation of the study regimen or interpretation of patient safety or study results&#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>Albiruni Razak, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Princess Margaret Cancer Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>February 1, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>November 26, 2021</last_update_submitted>
  <last_update_submitted_qc>November 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 9, 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>Sarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</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/NCT03042819
org study id: SAR-002
nct id: NCT03042819
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
This is a phase 1b study of investigational drug selinexor in combination with doxorubicin in
      patients with locally advanced or metastatic soft tissue sarcoma. The purpose of this study
      is to determine how safe and tolerable the combination is, as well as the best dose of the
      study drugs in this patient population.

      Selinexor (also called KPT-330), works by trapping "tumor suppressor proteins" within the
      cell and thus causing the cancer cells to die or stop growing.
This is a phase 1b study of investigational drug selinexor in combination with doxorubicin in
      patients with locally advanced or metastatic soft tissue sarcoma.

      Patients will be screened for eligibility within 28 days of the start of the study drugs. In
      addition to standard tests and procedures, research tumor tissue (archival or fresh biopsy)
      will be collected for collection for pharmacodynamics. Participants will also be asked if
      they agree to optional biopsies at 6 cycles if their cancer is responding and at disease
      progression.

      Eligible participants will then receive the study drugs in 21 day cycles. Selinexor will be
      given by mouth and doxorubicin will be given by vein, once a week, for 6 cycles.

      Participants will be restaged every 2 cycles. If participants respond to treatment after 6
      cycles, they may be able to continue the selinexor alone as a maintenance treatment until
      progression or unacceptable toxicity.

      While receiving the study drug, many of the screening tests will be repeated. Additional
      tests and procedures include blood sample collection for pharmacokinetics and
      pharmacodynamics.

      When participants stop the study drug permanently for any reason, an end of treatment visit,
      28-day follow-up, and long term follow up every 90 days will occur.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To evaluate the Incidence of Treatment-Emergent Adverse Events, graded and categorized according to the CTCAE v4.0.
time frame: 3 years
description: All adverse events will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution. SAE specific incidence and exact 95% confidence interval will be provided where appropriate.
measure: To determine the recommended phase II dose (RP2D) of Selinexor in combination with doxorubicin
time frame: 3 years
description: The RP2D will be determined according to interim mTPI monitoring algorithm (Figure 5.1) using the dose determining set.
measure: Rate of Grade 3 Toxicities
time frame: 3 years
measure: Response Rate
time frame: 3 years
measure: Progression-free Survival Rate
time frame: 3 years
arm group label: Selinexor plus Doxorubicin
arm group type: Experimental
description: Selinexor will be given by mouth (orally) once a week:
Dose Level -1 = 40 mg Dose Level 1 (Starting Dose) = 60 mg Dose Level 2 = 80 mg
Doxorubicin will be given by vein (intravenously) at a dose of 75 mg/m2 once every 3 weeks.
intervention type: Drug
intervention name: Selinexor
description: Selinexor is a Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1), thereby forcing the nuclear retention of key tumor suppressor proteins (TSPs).
arm group label: Selinexor plus Doxorubicin
intervention type: Drug
intervention name: Doxorubicin
description: Doxorubicin is currently approved for various cancers. Doxorubicin inhibits DNA synthesis and repair by inhibiting topoisomerase II and also by intercalation between base pairs on the DNA helix. These actions result in the blockade of DNA and RNA synthesis and fragmentation of DNA.
arm group label: Selinexor plus Doxorubicin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Albiruni Razak, M.D.
role: Principal Investigator
affiliation: Princess Margaret Cancer Centre
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Sarcoma
mesh term: Doxorubicin
sharing ipd: No