xml: <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/NCT05983276</url>
    </required_header>
    <id_info>
      <org_study_id>215615</org_study_id>
      <nct_id>NCT05983276</nct_id>
    </id_info>
    <brief_title>Decitabine and Selinexor in Combination to Reverse Drug Resistance With Standard Chemotherapy in Ovarian Cancer</brief_title>
    <official_title>Combination of the Hypomethylating Agent Decitabine and the Nuclear Export Receptor XPO-1 Inhibitor Selinexor to Reverse Platinum Resistance in Relapsed/Refractory Epithelial Ovarian Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Loyola University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Karyopharm Therapeutics Inc</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Loyola 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 goal of this clinical trial is to learn about the side effects and effectiveness of this&#xD;
        novel four-drug combination of chemotherapy (decitabine, selinexor, carboplatin and&#xD;
        paclitaxel) on patients with relapsed ovarian, fallopian or primary peritoneal carcinoma.&#xD;
  &#xD;
        Recently the investigators have found that the combination of decitabine and selinexor, two&#xD;
        Food and Drug Administration (FDA) approved chemotherapy agents, may prevent or reverse the&#xD;
        development of drug resistance and further the remissions and duration of remissions with&#xD;
        standard ovarian cancer chemotherapy with carboplatin and paclitaxel. As decitabine and&#xD;
        selinexor are not FDA approved for the participant's cancer, these agents are&#xD;
        investigational.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Participants enrolled in this study protocol will receive therapy with decitabine followed by&#xD;
        usual doses of carboplatin and paclitaxel for one cycle. If the participant tolerates this&#xD;
        well, the selinexor will be added to the second and subsequent cycles of therapy given at&#xD;
        4-week intervals, in the out-patient setting. The participant will be asked to complete 9&#xD;
        study visits during their active therapy during each cycle: Days 1-5 of each cycle the&#xD;
        participant will receive decitabine treatments over 1 hour, with carboplatin and paclitaxel&#xD;
        given on day 6. Paclitaxel alone will continue weekly for 3 weeks on days 13, 20 and 27 of&#xD;
        the 28-day cycle. The 5 days of daily decitabine therapy lasts about 1 hour and the&#xD;
        carboplatin and paclitaxel treatment last 4 hours, with single agent paclitaxel being only 1&#xD;
        hour.&#xD;
  &#xD;
        Selinexor is not added until cycle 2 and is given orally weekly on days 7, 14, 21, and 28 of&#xD;
        the 28-day cycle. Weekly clinic visits are required for the first two cycles at the time&#xD;
        paclitaxel is administered.&#xD;
  &#xD;
        The participant's progress will be assessed and if a remission is achieved the participant&#xD;
        would continue the therapy for up to 6 cycles.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 28, 2023</start_date>
    <completion_date type="Anticipated">August 28, 2031</completion_date>
    <primary_completion_date type="Anticipated">August 28, 2030</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>
      <intervention_model_description>Once selected for therapy, the participant will receive the following treatment in the outpatient setting:&#xD;
  Days 1-5: Decitabine 10 mg; m2 IV daily Day 6: carboplatin AUC 5 and paclitaxel 80 mg; m2 Days 13, 20, and 27: paclitaxel 80 mg/m2 For a single 28 day cycle.&#xD;
  Assess Response toxicities and immune effector cell changes.&#xD;
  Days 1-5: Decitabine 10 mg/m2 IV daily; Day 6: carboplatin AUC 5 and paclitaxel 80 mg/ m2; Day 7 and weekly thereafter (day 14, 21, 28, 35…) Selinexor 60 mg PO Days 13, 20, and 27: paclitaxel 80 mg/m2 each given x five 28 day cycles&#xD;
  Assess responses by exam, CT scan and blood tests, assess toxicities, and immune effector cell changes as well as progression and overall survival</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>40 participants evaluated for safety with treatment-related adverse events and grading using CTCAE 4.3.</measure>
      <time_frame>6 months</time_frame>
      <description>To determine the safety of two agents in combination to reverse platinum resistance in ovarian cancer: the hypomethylating agent, decitabine, and the nuclear export receptor XPO1 inhibitor, selinexor, combined with carboplatin and paclitaxel in patients with relapsed/refractory epithelial ovarian carcinoma</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>40 participants evaluated to determine the clinical efficacy of this novel regimen in both platinum sensitive and resistant recurrent disease as measured by response rates. Response rates (partial response [PR] and complete response [CR])</measure>
      <time_frame>6 months</time_frame>
      <description>To determine the clinical efficacy of this novel regimen in both platinum sensitive and resistant disease as measured by response rates</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>40 participants evaluated to determine the cellular immune effects of this combination. B and T cell numbers and subsets after therapy.</measure>
      <time_frame>6 months</time_frame>
      <description>This is an exploratory endpoint to determine if there is a potential immune enhancement of this combination on numbers of Immune T and B cells after therapy (15% or higher increase in cell numbers/mm3) when compared to pre-treatment values and whether this correlates to response rates.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>40 participants evaluated for tolerability with treatment-related adverse events and grading using CTCAE 4.3.</measure>
      <time_frame>6 months</time_frame>
      <description>To determine the tolerability of two agents that reverse platinum sensitivity in ovarian cancer, the hypomethylating agent, decitabine, and the nuclear export receptor XPO1 inhibitor, Selinexor, combined with carboplatin and Taxol in patients with relapsed/refractory epithelial ovarian carcinoma</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Ovarian Cancer</condition>
    <arm_group>
      <arm_group_label>Decitabine / Selinexor/ Carboplatin / Paclitaxel</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>C1:&#xD;
  Days 1-5: Decitabine 10 mg/m2 IV daily Day 6: carboplatin AUC 5 and paclitaxel 80 mg/ m2 Days 13, 20, and 27: paclitaxel 80 mg/m2 For a single 28 day cycle&#xD;
  Assess Response toxicities and immune effector cell changes&#xD;
  C2-C6:&#xD;
  Days 1-5: Decitabine 10 mg/m2 IV daily Day 6: carboplatin AUC 5 and paclitaxel 80 mg/ m2 Day 7 and weekly thereafter (day 14, 21, 28, 35…) Selinexor 60 mg PO Days 13, 20, and 27: paclitaxel 80 mg/m2 each given x five 28 day cycles&#xD;
  Assess responses by exam, CT scan and blood tests, assess toxicities, and immune effector cell changes as well as progression and overall survival</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Decitabine</intervention_name>
      <description>Decitabine is classified as hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow.</description>
      <arm_group_label>Decitabine / Selinexor/ Carboplatin / Paclitaxel</arm_group_label>
      <other_name>Dacogen</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Carboplatin</intervention_name>
      <description>Carboplatin is classified as an alkylating agent that is used to treat ovarian cancer.</description>
      <arm_group_label>Decitabine / Selinexor/ Carboplatin / Paclitaxel</arm_group_label>
      <other_name>Paraplatin</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Paclitaxel</intervention_name>
      <description>Paclitaxel is classified as a &quot;plant alkaloid,&quot; a &quot;taxane&quot; and an &quot;antimicrotubule agent.&quot;</description>
      <arm_group_label>Decitabine / Selinexor/ Carboplatin / Paclitaxel</arm_group_label>
      <other_name>Abraxane</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Selinexor</intervention_name>
      <description>Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by killing cancer cells.</description>
      <arm_group_label>Decitabine / Selinexor/ Carboplatin / Paclitaxel</arm_group_label>
      <other_name>Xpovio, Nexpovio</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Participants must be greater than or equal to 18 years of age&#xD;
  &#xD;
            -  Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status&#xD;
               PS less than or equal to 2.&#xD;
  &#xD;
            -  Participants must have histological or cytological proven epithelial ovarian cancer,&#xD;
               fallopian tube or primary peritoneal carcinoma with relapse or disease progression&#xD;
               after prior treatment by exam, computed tomography (CT), PET/CT, or magnetic resonance&#xD;
               imaging (MRI) may be enrolled. All cell types including clear cell carcinoma are&#xD;
               eligible.&#xD;
  &#xD;
            -  Participants must have failed or relapsed after a platinum and taxane containing&#xD;
               combination&#xD;
  &#xD;
            -  Participants must have adequate hepatic function&#xD;
  &#xD;
            -  Participants must have adequate renal function&#xD;
  &#xD;
            -  Participants must be able to swallow and retain oral medications&#xD;
  &#xD;
            -  Participants must have measurable disease according to Gynecologic Cancer Intergroup&#xD;
               CA125 criteria&#xD;
  &#xD;
            -  Participants with stable (for 2 months or longer), treated (by radiotherapy) CNS&#xD;
               metastases are eligible&#xD;
  &#xD;
            -  Participants with active hepatitis B virus (Hep B) are allowed if antiviral therapy&#xD;
               for hepatitis B has been given for greater than 8 weeks.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Participants must not have received Selinexor or another XPO1 inhibitor previously.&#xD;
  &#xD;
            -  Participants must not have had any concurrent medical condition or disease (eg,&#xD;
               uncontrolled active hypertension, uncontrolled active diabetes, active systemic&#xD;
               infection, etc.)&#xD;
  &#xD;
            -  Participants must not have uncontrolled active infection. Participants on prophylactic&#xD;
               antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.&#xD;
  &#xD;
            -  Participants must not have known intolerance, hypersensitivity, or contraindication to&#xD;
               platinum or taxane therapy&#xD;
  &#xD;
            -  Participants must not have active, unstable cardiovascular function&#xD;
  &#xD;
            -  Participants must not have myocardial infarction within 3 months prior to starting&#xD;
  &#xD;
            -  Participants with untreated central nervous system (CNS) metastases are ineligible.&#xD;
  &#xD;
            -  Participants must not have had prior chemotherapy or radiation therapy&#xD;
  &#xD;
            -  Participants must not have DVT related to metastatic disease requiring ongoing&#xD;
               anticoagulation.&#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>Patrick L Stiff, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Loyola University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Patrick Stiff, MD</last_name>
      <phone>708-327-3148</phone>
      <email>pstiff@lumc.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Agnes Natonton, RN</last_name>
      <phone>708-327-3383</phone>
      <email>anatont@luc.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Loyola University Medical Center</name>
        <address>
          <city>Maywood</city>
          <state>Illinois</state>
          <zip>60153</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 12, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Loyola University</investigator_affiliation>
      <investigator_full_name>Patrick Stiff</investigator_full_name>
      <investigator_title>Senior Professor</investigator_title>
    </responsible_party>
    <keyword>Ovarian Cancer</keyword>
    <keyword>Platinum Resistance</keyword>
    <keyword>Relapsed/Refractory Epithelial</keyword>
    <keyword>Fallopian Tube</keyword>
    <keyword>Primary Peritoneal Cancer</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Ovarian Neoplasms</mesh_term>
      <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Paclitaxel</mesh_term>
      <mesh_term>Carboplatin</mesh_term>
      <mesh_term>Decitabine</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05983276
  org study id: 215615
  nct id: NCT05983276
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The goal of this clinical trial is to learn about the side effects and effectiveness of this
        novel four-drug combination of chemotherapy (decitabine, selinexor, carboplatin and
        paclitaxel) on patients with relapsed ovarian, fallopian or primary peritoneal carcinoma.
  
        Recently the investigators have found that the combination of decitabine and selinexor, two
        Food and Drug Administration (FDA) approved chemotherapy agents, may prevent or reverse the
        development of drug resistance and further the remissions and duration of remissions with
        standard ovarian cancer chemotherapy with carboplatin and paclitaxel. As decitabine and
        selinexor are not FDA approved for the participant's cancer, these agents are
        investigational.
  Participants enrolled in this study protocol will receive therapy with decitabine followed by
        usual doses of carboplatin and paclitaxel for one cycle. If the participant tolerates this
        well, the selinexor will be added to the second and subsequent cycles of therapy given at
        4-week intervals, in the out-patient setting. The participant will be asked to complete 9
        study visits during their active therapy during each cycle: Days 1-5 of each cycle the
        participant will receive decitabine treatments over 1 hour, with carboplatin and paclitaxel
        given on day 6. Paclitaxel alone will continue weekly for 3 weeks on days 13, 20 and 27 of
        the 28-day cycle. The 5 days of daily decitabine therapy lasts about 1 hour and the
        carboplatin and paclitaxel treatment last 4 hours, with single agent paclitaxel being only 1
        hour.
  
        Selinexor is not added until cycle 2 and is given orally weekly on days 7, 14, 21, and 28 of
        the 28-day cycle. Weekly clinic visits are required for the first two cycles at the time
        paclitaxel is administered.
  
        The participant's progress will be assessed and if a remission is achieved the participant
        would continue the therapy for up to 6 cycles.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Once selected for therapy, the participant will receive the following treatment in the outpatient setting:
  Days 1-5: Decitabine 10 mg; m2 IV daily Day 6: carboplatin AUC 5 and paclitaxel 80 mg; m2 Days 13, 20, and 27: paclitaxel 80 mg/m2 For a single 28 day cycle.
  Assess Response toxicities and immune effector cell changes.
  Days 1-5: Decitabine 10 mg/m2 IV daily; Day 6: carboplatin AUC 5 and paclitaxel 80 mg/ m2; Day 7 and weekly thereafter (day 14, 21, 28, 35…) Selinexor 60 mg PO Days 13, 20, and 27: paclitaxel 80 mg/m2 each given x five 28 day cycles
  Assess responses by exam, CT scan and blood tests, assess toxicities, and immune effector cell changes as well as progression and overall survival
  primary purpose: Treatment
  masking: None (Open Label)
  measure: 40 participants evaluated for safety with treatment-related adverse events and grading using CTCAE 4.3.
  time frame: 6 months
  description: To determine the safety of two agents in combination to reverse platinum resistance in ovarian cancer: the hypomethylating agent, decitabine, and the nuclear export receptor XPO1 inhibitor, selinexor, combined with carboplatin and paclitaxel in patients with relapsed/refractory epithelial ovarian carcinoma
  measure: 40 participants evaluated to determine the clinical efficacy of this novel regimen in both platinum sensitive and resistant recurrent disease as measured by response rates. Response rates (partial response [PR] and complete response [CR])
  time frame: 6 months
  description: To determine the clinical efficacy of this novel regimen in both platinum sensitive and resistant disease as measured by response rates
  measure: 40 participants evaluated to determine the cellular immune effects of this combination. B and T cell numbers and subsets after therapy.
  time frame: 6 months
  description: This is an exploratory endpoint to determine if there is a potential immune enhancement of this combination on numbers of Immune T and B cells after therapy (15% or higher increase in cell numbers/mm3) when compared to pre-treatment values and whether this correlates to response rates.
  measure: 40 participants evaluated for tolerability with treatment-related adverse events and grading using CTCAE 4.3.
  time frame: 6 months
  description: To determine the tolerability of two agents that reverse platinum sensitivity in ovarian cancer, the hypomethylating agent, decitabine, and the nuclear export receptor XPO1 inhibitor, Selinexor, combined with carboplatin and Taxol in patients with relapsed/refractory epithelial ovarian carcinoma
  arm group label: Decitabine / Selinexor/ Carboplatin / Paclitaxel
  arm group type: Experimental
  description: C1:
  Days 1-5: Decitabine 10 mg/m2 IV daily Day 6: carboplatin AUC 5 and paclitaxel 80 mg/ m2 Days 13, 20, and 27: paclitaxel 80 mg/m2 For a single 28 day cycle
  Assess Response toxicities and immune effector cell changes
  C2-C6:
  Days 1-5: Decitabine 10 mg/m2 IV daily Day 6: carboplatin AUC 5 and paclitaxel 80 mg/ m2 Day 7 and weekly thereafter (day 14, 21, 28, 35…) Selinexor 60 mg PO Days 13, 20, and 27: paclitaxel 80 mg/m2 each given x five 28 day cycles
  Assess responses by exam, CT scan and blood tests, assess toxicities, and immune effector cell changes as well as progression and overall survival
  intervention type: Drug
  intervention name: Decitabine
  description: Decitabine is classified as hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow.
  arm group label: Decitabine / Selinexor/ Carboplatin / Paclitaxel
  other name: Dacogen
  intervention type: Drug
  intervention name: Carboplatin
  description: Carboplatin is classified as an alkylating agent that is used to treat ovarian cancer.
  arm group label: Decitabine / Selinexor/ Carboplatin / Paclitaxel
  other name: Paraplatin
  intervention type: Drug
  intervention name: Paclitaxel
  description: Paclitaxel is classified as a "plant alkaloid," a "taxane" and an "antimicrotubule agent."
  arm group label: Decitabine / Selinexor/ Carboplatin / Paclitaxel
  other name: Abraxane
  intervention type: Drug
  intervention name: Selinexor
  description: Selinexor is in a class of medications called selective inhibitors of nuclear export (SINE). It works by killing cancer cells.
  arm group label: Decitabine / Selinexor/ Carboplatin / Paclitaxel
  other name: Xpovio, Nexpovio
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Patrick L Stiff, MD
  role: Principal Investigator
  affiliation: Loyola University
  last name: Patrick Stiff, MD
  phone: 708-327-3148
  email: pstiff@lumc.edu
  last name: Agnes Natonton, RN
  phone: 708-327-3383
  email: anatont@luc.edu
  facility: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Loyola University
  investigator full name: Patrick Stiff
  investigator title: Senior Professor
  mesh term: Ovarian Neoplasms
  mesh term: Carcinoma, Ovarian Epithelial
  mesh term: Paclitaxel
  mesh term: Carboplatin
  mesh term: Decitabine