<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/NCT01676818</url>
  </required_header>
  <id_info>
    <org_study_id>5C-11-2</org_study_id>
    <secondary_id>NCI-2012-01378</secondary_id>
    <nct_id>NCT01676818</nct_id>
  </id_info>
  <brief_title>Eribulin Mesylate in Treating Patients With Advanced or Recurrent Cervical Cancer</brief_title>
  <official_title>Phase II Clinical Trial of Eribulin in Advanced or Recurrent Cervical Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Southern California</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Southern California</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 phase II trial studies how well eribulin mesylate works in treating patients with&#xD;
      advanced or recurrent cervical cancer. Drugs used in chemotherapy, such as eribulin mesylate,&#xD;
      work in different ways to stop the growth of tumor cells, either by killing the cells or by&#xD;
      stopping them from dividing&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the activity of eribulin (eribulin mesylate) in the management of advanced or&#xD;
      recurrent cervical cancer (progression-free survival [PFS].&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To describe the toxicity profile of eribulin in patients with advanced or recurrent&#xD;
      cervical cancer.&#xD;
&#xD;
      II. To estimate the survival of patients with advanced or recurrent cervical cancer treated&#xD;
      with eribulin.&#xD;
&#xD;
      III. To evaluate potential correlative studies as predictive or prognostic makers in this&#xD;
      patient population (glucose-regulated protein 78 [GRP78] levels in tissue and blood, tumor&#xD;
      protein p53 [p53] expression, apoptosis with terminal deoxynucleotidyl transferase dUTP nick&#xD;
      end labeling [TUNEL] assay, apoptosis-related proteins B-cell lymphoma 2 [Bcl-2] and&#xD;
      Bcl2-associated X protein [Bax] using immunohistochemistry [IHC], proliferation with Ki-67&#xD;
      IHC, and expression levels of microtubule-associated variables, including tau protein, total&#xD;
      alpha- and beta-tubulin, and classes II-IV beta-tubulin isotopes with IHC.&#xD;
&#xD;
      OUTLINE: Patients receive eribulin mesylate 1.4 mg/m2 intravenously (IV) bolus over 2-5&#xD;
      minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression&#xD;
      or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 9, 2012</start_date>
  <completion_date type="Actual">August 9, 2021</completion_date>
  <primary_completion_date type="Actual">February 21, 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>Progression-free survival</measure>
    <time_frame>From the first day of treatment to the first observation of disease progression or death due to any cause, assessed at 6 months</time_frame>
    <description>Product limits estimates of 6-month PFS will be computed using all patients enrolled on the study. 95% confidence intervals will be based on Greenwood standard errors.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with serious adverse events (SAEs)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>The rate of grade 3+ hematologic and non-hematologic toxicities will be computed for course 1 and for all courses combined. Safety evaluation according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.3.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Best overall response (BOR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Exact 95% binomial confidence intervals will be computed for the BOR rate. BOR defined as the best response recorded from the start of treatment until disease progression/recurrence, evaluated according to RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From first day of treatment to time of death due to any cause, assessed up to 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Recurrent Cervical Cancer</condition>
  <condition>Stage IIIA Cervical Cancer</condition>
  <condition>Stage IIIB Cervical Cancer</condition>
  <condition>Stage IVA Cervical Cancer</condition>
  <condition>Stage IVB Cervical Cancer</condition>
  <arm_group>
    <arm_group_label>Eribulin mesylate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eribulin mesylate 1.4 mg/m2 IV bolus over 2-5 minutes on days 1 and 8 every 21 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>eribulin mesylate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Eribulin mesylate</arm_group_label>
    <other_name>B1939</other_name>
    <other_name>E7389</other_name>
    <other_name>ER-086526</other_name>
    <other_name>halichrondrin B analog</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed diagnosis of invasive cervical cancer&#xD;
&#xD;
          -  Measurable disease&#xD;
&#xD;
          -  0-1 prior chemotherapy regimens for recurrent or advanced disease; platinum based&#xD;
             chemotherapy administered as a radiation sensitizer agent is allowed and does not&#xD;
             count as prior therapy&#xD;
&#xD;
          -  Absolute granulocyte count (AGC) &gt;= 1,500&#xD;
&#xD;
          -  Platelet &gt;= 100,000&#xD;
&#xD;
          -  Serum creatinine &lt; 2.0 mg/dl&#xD;
&#xD;
          -  Bilirubin =&lt; 1.5 times the upper limit of the normal range (ULN)&#xD;
&#xD;
          -  Alkaline phosphatase =&lt; 3 x ULN (in the case of liver metastases, =&lt; 5 x ULN)&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 3 x ULN (in the&#xD;
             case of liver metastases, =&lt; 5 x ULN)&#xD;
&#xD;
          -  Peripheral neuropathy grade 0-2&#xD;
&#xD;
          -  Recovery of all chemotherapy or radiation-related toxicities to grade =&lt; 1, except for&#xD;
             alopecia and peripheral neuropathy&#xD;
&#xD;
          -  Performance status 0-2&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with eribulin&#xD;
&#xD;
          -  Chemotherapy, radiation, or biological or targeted therapy within 3 weeks&#xD;
&#xD;
          -  Hormonal therapy within 1 week&#xD;
&#xD;
          -  Any investigational drug within 4 weeks&#xD;
&#xD;
          -  Known brain metastases, unless previously treated and asymptomatic for 3 months and&#xD;
             not progressive in size or number for 3 months&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lynda Roman, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southern California</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>USC Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 31, 2012</study_first_posted>
  <last_update_submitted>November 12, 2021</last_update_submitted>
  <last_update_submitted_qc>November 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 15, 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>Uterine Cervical Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <!-- 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/NCT01676818
org study id: 5C-11-2
secondary id: NCI-2012-01378
nct id: NCT01676818
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well eribulin mesylate works in treating patients with
      advanced or recurrent cervical cancer. Drugs used in chemotherapy, such as eribulin mesylate,
      work in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing
PRIMARY OBJECTIVES:

      I. To evaluate the activity of eribulin (eribulin mesylate) in the management of advanced or
      recurrent cervical cancer (progression-free survival [PFS].

      SECONDARY OBJECTIVES:

      I. To describe the toxicity profile of eribulin in patients with advanced or recurrent
      cervical cancer.

      II. To estimate the survival of patients with advanced or recurrent cervical cancer treated
      with eribulin.

      III. To evaluate potential correlative studies as predictive or prognostic makers in this
      patient population (glucose-regulated protein 78 [GRP78] levels in tissue and blood, tumor
      protein p53 [p53] expression, apoptosis with terminal deoxynucleotidyl transferase dUTP nick
      end labeling [TUNEL] assay, apoptosis-related proteins B-cell lymphoma 2 [Bcl-2] and
      Bcl2-associated X protein [Bax] using immunohistochemistry [IHC], proliferation with Ki-67
      IHC, and expression levels of microtubule-associated variables, including tau protein, total
      alpha- and beta-tubulin, and classes II-IV beta-tubulin isotopes with IHC.

      OUTLINE: Patients receive eribulin mesylate 1.4 mg/m2 intravenously (IV) bolus over 2-5
      minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression
      or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival
time frame: From the first day of treatment to the first observation of disease progression or death due to any cause, assessed at 6 months
description: Product limits estimates of 6-month PFS will be computed using all patients enrolled on the study. 95% confidence intervals will be based on Greenwood standard errors.
measure: Number of participants with serious adverse events (SAEs)
time frame: Up to 2 years
description: The rate of grade 3+ hematologic and non-hematologic toxicities will be computed for course 1 and for all courses combined. Safety evaluation according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.3.
measure: Best overall response (BOR)
time frame: Up to 2 years
description: Exact 95% binomial confidence intervals will be computed for the BOR rate. BOR defined as the best response recorded from the start of treatment until disease progression/recurrence, evaluated according to RECIST 1.1.
measure: Overall survival (OS)
time frame: From first day of treatment to time of death due to any cause, assessed up to 2 years
arm group label: Eribulin mesylate
arm group type: Experimental
description: Eribulin mesylate 1.4 mg/m2 IV bolus over 2-5 minutes on days 1 and 8 every 21 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: eribulin mesylate
description: Given IV
arm group label: Eribulin mesylate
other name: B1939
other name: E7389
other name: ER-086526
other name: halichrondrin B analog
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lynda Roman, MD
role: Principal Investigator
affiliation: University of Southern California
facility: 
country: United States
responsible party type: Sponsor
mesh term: Uterine Cervical Neoplasms
mesh term: Recurrence