<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/NCT01711034</url>
  </required_header>
  <id_info>
    <org_study_id>317-11-201</org_study_id>
    <nct_id>NCT01711034</nct_id>
  </id_info>
  <brief_title>A Phase 1, Open-label, Multiple Dose Escalation Trial to Determine Safety and Tolerability of Once Daily OPB-111077 in Subjects With Advanced Cancer</brief_title>
  <official_title>A Phase 1, Open-label, Multiple Dose Escalation Trial to Determine Safety and Tolerability of Once Daily OPB-111077 in Subjects With Advanced Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to determine the safe and tolerable dose level of&#xD;
      OPB-111077 for patients with advanced cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The secondary objective of this study is to investigate the pharmacokinetic properties of&#xD;
      OPB-111077; the pharmacodynamic effects of OPB-111077; the antitumor activity of OPB-111077&#xD;
      as assessed by RECIST or IMWG Uniform Response Criteria; and to explore whether PET responses&#xD;
      correlate with other measures of clinical response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</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>Safety and tolerability of OPB-111077</measure>
    <time_frame>28 Days</time_frame>
    <description>AEs, Vital signs,Body weight, ECGs, Laboratory tests, Performance status</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To determine the pharmacokinetics of OPB-111077</measure>
    <time_frame>28 Days</time_frame>
    <description>The following PK parameters for Food-effect Sub-study (Cmax, AUCtau,AUCt, tmax, CLss/F and t1/2,z) will be determined using a non-compartmental approach for OPB-111077 and selected metabolites after single (Cycle 1, Day 1) and multiple daily doses (Cycle 2, Day 1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamic profile</measure>
    <time_frame>28 Days</time_frame>
    <description>Study drug effects on STAT3 phosphorylation in response to IL-6 will be measured in PBMCs from subjects treated with OPB-111077.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antitumor effects</measure>
    <time_frame>Assessments will be conducted at Screening, Cycle 3, every 2 cycles (+/- 1 week) thereafter, at the Final/Early Termination Visit, and at the 30-day Follow-up Visit.</time_frame>
    <description>Subjects with measurable disease will be assessed by RECIST Assessments will be conducted at Screening, Cycle 3, every 2 cycles (+/- 1 week) thereafter, at the Final/Early Termination Visit, and at the 30-day Follow-up Visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine the MTD of OPB-111077</measure>
    <time_frame>Within the first cycle [28 days].</time_frame>
    <description>The highest dose at which fewer than 2 of 6 subjects experience DLT during the first 28 day cycle.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PET Sub-study (Part C)</measure>
    <time_frame>2 weeks</time_frame>
    <description>A sub-study of up to 24 patients with PET-avid tumors where additional PET scans are performed to explore intra-subject PET activity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Food-effect Sub-study (Part B)</measure>
    <time_frame>11 days</time_frame>
    <description>An open-label, two-period crossover arm, for pre-selected study sites to determine the effect of food on the rate and extent of absorption (PK) following single dose 250mg OPB-111077.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">145</enrollment>
  <condition>Solid Tumors</condition>
  <arm_group>
    <arm_group_label>OPB-111077</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In escalation stage of study, treatment with a once daily dose of OPB-111077 during cycles 1 and 2 on day 1, followed by 2-day treatment free interval, and then resuming daily dosing on day 4 through day 28. For cycle 3 and beyond, OPB-111077 will be administered for 28 continuous days per cycle until MTD is reached.&#xD;
In expansion portion of study, established dose of 250mg administered once daily for 28 consecutive days for each cycle. Patient in expansion are defined as those who meet eligibility criteria and have a diagnosed malignancy that is presumed to be susceptible to inhibition by OPB-111077</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OPB-111077</intervention_name>
    <description>Dose escalation phase starting with dose of 100mg tablets on Day 1 and 4, and all remaining days of each 28 day cycle until disease progression or toxicity develops.&#xD;
Dose expansion phase starting with daily dosing of 250mg for 28 day consecutive day cycles.</description>
    <arm_group_label>OPB-111077</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically and/or cytologically confirmed advanced malignancy that is refractory&#xD;
             to standard therapy or for which there are no standard treatment options available&#xD;
&#xD;
          -  For oral or intravenous anticancer therapies, at least 4 weeks or 5 half-lives,&#xD;
             whichever is shorter, need to have elapsed since the last dose&#xD;
&#xD;
          -  Recovery from adverse effects of prior therapy at time of enrollment to&#xD;
&#xD;
             o ≤ Grade 1 (excluding alopecia)&#xD;
&#xD;
          -  Agreement to forego any other chemotherapy, immunotherapy, radiotherapy, or&#xD;
             investigational drug while enrolled on this trial except hormonal therapy for prostate&#xD;
             cancer or radiotherapy for symptomatic bone metastases known to be present at&#xD;
             Screening&#xD;
&#xD;
          -  Male or female subjects aged ≥ 18 years&#xD;
&#xD;
          -  ECOG performance status ≤ 2&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
          -  Life expectancy of ≥ 3 months following trial entry&#xD;
&#xD;
          -  For women of childbearing potential, a negative serum pregnancy test result at&#xD;
             Screening&#xD;
&#xD;
          -  For women of childbearing potential or men whose sexual partners are women of&#xD;
             childbearing potential, agreement to use 2 methods of adequate contraception prior to&#xD;
             trial entry, for the duration of the trial, and for 90 days after the last dose of&#xD;
             trial medication&#xD;
&#xD;
          -  Signed and dated IRB-approved informed consent prior to any performance of&#xD;
             protocol-specific screening procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled concurrent illness, including but not limited to: ongoing or active&#xD;
             infection; uncontrolled heart, liver, kidney, or endocrine disorder&#xD;
&#xD;
          -  Altered mental status, psychiatric illness, or social situation that would limit&#xD;
             compliance with trial requirements and/or obscure trial results&#xD;
&#xD;
          -  Immunocompromised state&#xD;
&#xD;
          -  Known or evidence of chronic viral hepatitis (hepatitis B or C virus)&#xD;
&#xD;
          -  Untreated or symptomatic brain metastasis, or subjects with leptomeningeal disease&#xD;
&#xD;
          -  Inability to swallow oral meds or gastrointestinal disorder that might interfere with&#xD;
             absorption of oral drugs&#xD;
&#xD;
          -  Major surgery within 28 days of first receipt of trial drug&#xD;
&#xD;
          -  Nursing or pregnant women&#xD;
&#xD;
          -  ≥ Grade 1 neuropathy with pain or &gt; Grade 2 neuropathy without pain (subjects with&#xD;
             neuropathy caused by a previous regimen that is recovered to ≤ Grade 2 and stable&#xD;
             without pain may be included)&#xD;
&#xD;
          -  Food-effect sub-study (Part B) only: Pathologies or medical histories that might&#xD;
             impair absorption and elimination.&#xD;
&#xD;
          -  PET scan sub-study (Part C) only: Uncontrollable blood glucose or intolerance to PET&#xD;
             scan procedures.&#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>Edwin Rock, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>October 12, 2012</study_first_submitted>
  <study_first_submitted_qc>October 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <last_update_submitted>April 1, 2016</last_update_submitted>
  <last_update_submitted_qc>April 1, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 5, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Solid tumors</keyword>
  <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/NCT01711034
org study id: 317-11-201
nct id: NCT01711034
lead sponsor: 
has dmc: No
The primary objective of this study is to determine the safe and tolerable dose level of
      OPB-111077 for patients with advanced cancer.
The secondary objective of this study is to investigate the pharmacokinetic properties of
      OPB-111077; the pharmacodynamic effects of OPB-111077; the antitumor activity of OPB-111077
      as assessed by RECIST or IMWG Uniform Response Criteria; and to explore whether PET responses
      correlate with other measures of clinical response.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability of OPB-111077
time frame: 28 Days
description: AEs, Vital signs,Body weight, ECGs, Laboratory tests, Performance status
measure: To determine the pharmacokinetics of OPB-111077
time frame: 28 Days
description: The following PK parameters for Food-effect Sub-study (Cmax, AUCtau,AUCt, tmax, CLss/F and t1/2,z) will be determined using a non-compartmental approach for OPB-111077 and selected metabolites after single (Cycle 1, Day 1) and multiple daily doses (Cycle 2, Day 1).
measure: Pharmacodynamic profile
time frame: 28 Days
description: Study drug effects on STAT3 phosphorylation in response to IL-6 will be measured in PBMCs from subjects treated with OPB-111077.
measure: Antitumor effects
time frame: Assessments will be conducted at Screening, Cycle 3, every 2 cycles (+/- 1 week) thereafter, at the Final/Early Termination Visit, and at the 30-day Follow-up Visit.
description: Subjects with measurable disease will be assessed by RECIST Assessments will be conducted at Screening, Cycle 3, every 2 cycles (+/- 1 week) thereafter, at the Final/Early Termination Visit, and at the 30-day Follow-up Visit.
measure: To determine the MTD of OPB-111077
time frame: Within the first cycle [28 days].
description: The highest dose at which fewer than 2 of 6 subjects experience DLT during the first 28 day cycle.
measure: PET Sub-study (Part C)
time frame: 2 weeks
description: A sub-study of up to 24 patients with PET-avid tumors where additional PET scans are performed to explore intra-subject PET activity.
measure: Food-effect Sub-study (Part B)
time frame: 11 days
description: An open-label, two-period crossover arm, for pre-selected study sites to determine the effect of food on the rate and extent of absorption (PK) following single dose 250mg OPB-111077.
arm group label: OPB-111077
arm group type: Experimental
description: In escalation stage of study, treatment with a once daily dose of OPB-111077 during cycles 1 and 2 on day 1, followed by 2-day treatment free interval, and then resuming daily dosing on day 4 through day 28. For cycle 3 and beyond, OPB-111077 will be administered for 28 continuous days per cycle until MTD is reached.
In expansion portion of study, established dose of 250mg administered once daily for 28 consecutive days for each cycle. Patient in expansion are defined as those who meet eligibility criteria and have a diagnosed malignancy that is presumed to be susceptible to inhibition by OPB-111077
intervention type: Drug
intervention name: OPB-111077
description: Dose escalation phase starting with dose of 100mg tablets on Day 1 and 4, and all remaining days of each 28 day cycle until disease progression or toxicity develops.
Dose expansion phase starting with daily dosing of 250mg for 28 day consecutive day cycles.
arm group label: OPB-111077
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Edwin Rock, MD, PhD
role: Study Director
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No