<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/NCT02988648</url>
  </required_header>
  <id_info>
    <org_study_id>1607018035</org_study_id>
    <nct_id>NCT02988648</nct_id>
  </id_info>
  <brief_title>A Clinical Trial Evaluating the Safety and Clinical Activity of Radioiodide (131I-) as a Novel Targeted Therapy for Metastatic Breast Cancer That Overexpresses Functional Na/I Symporter</brief_title>
  <official_title>A Phase I/II Clinical Trial Evaluating the Safety and Clinical Activity of Radioiodide (131I-) as a Novel Targeted Therapy for Metastatic Breast Cancer That Overexpresses Functional Na/I Symporter</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this phase I/II study is to evaluate the safety and clinical activity of&#xD;
      Radioiodide (131I-) as a novel targeted therapy for metastatic breast cancer that&#xD;
      overexpresses functional Na/I symporter. The study will enroll patients with metastatic&#xD;
      breast cancer who have had clinical and/or radiographic evidence of disease progression on&#xD;
      prior hormonal and/or chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objectives of the study are as follows:&#xD;
&#xD;
        1. To evaluate the feasibility of using 124I- PET/CT scans to identify patients whose&#xD;
           metastatic lesions accumulate radioactive iodide and therefore are candidates for 131I-&#xD;
           therapy.&#xD;
&#xD;
        2. Determine the frequency of iodide (124I) enriching metastatic breast cancer.&#xD;
&#xD;
        3. Evaluate the safety and clinical activity of one-time 131I treatment to patients who&#xD;
           screen positive on 124I- PET/CT screening, positivity is defined as calculated iodide&#xD;
           enrichment that will allow delivering 2000 cGy or more radiation to one or more&#xD;
           metastatic lesion by administering up to 200mCi 131I-.&#xD;
&#xD;
      The secondary objectives of the study are as follows:&#xD;
&#xD;
      1. To investigate a correlation between NIS expression in tumor tissue with 124I- uptake on&#xD;
      screening PET/CT scan&#xD;
&#xD;
      The Phase I portion will follow a 3+3 design with 4 dose levels (30, 60, 120, and 200 mCi) of&#xD;
      I- treatment. The maximum tolerated dose will be used in the Phase II efficacy assessment&#xD;
      which will follow a Simon's optimal two-stage design. The primary efficacy measure is&#xD;
      objective tumor response rate (CR or PR) with targeted activity level of &gt; 20% response rate.&#xD;
&#xD;
      The study will be terminated for futility if no tumor response is seen in the first 12&#xD;
      patients. If futility criteria is not met, a total of 37 eligible patients will be enrolled&#xD;
      in the Phase II portion. If 4 or more responses are seen after 37 patients were evaluated,&#xD;
      then the investigators will conclude that the regimen warrants further study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    The study was withdrawn due to lack of enrollment.&#xD;
  </why_stopped>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">January 2018</completion_date>
  <primary_completion_date type="Actual">January 2018</primary_completion_date>
  <phase>Phase 1/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>objective tumor response rate</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>The primary efficacy measure is objective tumor response rate (CR or PR) with targeted activity level of &gt; 20% response rate.&#xD;
Patients should be followed regularly until disease progression and until resolution of all acute toxicities associated with treatment administration. If stable disease or resolution of toxicities takes longer than 24 weeks, follow up frequency will be determined by the treating physician.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>radioiodide (I-)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The Phase I portion will follow a 3+3 design with 4 dose levels (30, 60, 120, and 200 mCi) of I- treatment. The maximum tolerated dose (from Phase I) will be used in the Phase II efficacy assessment which will follow a Simon's optimal two-stage design.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radioiodide (131I-)</intervention_name>
    <description>The Phase I portion will follow a 3+3 design with 4 dose levels (30, 60, 120, and 200 mCi) of I- treatment. The maximum tolerated dose (from Phase I) will be used in the Phase II efficacy assessment which will follow a Simon's optimal two-stage design.</description>
    <arm_group_label>radioiodide (I-)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Each patient must meet all inclusion criteria in order to be considered for enrollment:&#xD;
&#xD;
          -  Histologically confirmed breast cancer with clinical and/or radiological evidence of&#xD;
             measurable or evaluable metastatic disease by Response Evaluation in Solid Tumors&#xD;
             (RECIST) 1.1.&#xD;
&#xD;
          -  Life expectancy ≥12 weeks.&#xD;
&#xD;
          -  Radiologic or clinical evidence of disease progression on prior hormonal and/or&#xD;
             chemotherapy&#xD;
&#xD;
          -  There is no restriction on the number of prior lines of therapy.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status score of &lt; 2.&#xD;
&#xD;
          -  Full recovery to Grade ≤ 2 from any prior side effects of prior therapy for cancer&#xD;
             including radiation therapy, chemotherapy, and/or immunotherapy.&#xD;
&#xD;
          -  Adequate bone marrow function defined as white blood cells (WBCs) ≥ 3.0 × 109/L,&#xD;
             neutrophils ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L.&#xD;
&#xD;
          -  Adequate renal function defined as serum creatinine &lt; 1.5 mg/dL or creatinine&#xD;
             clearance (GFR) &gt; 40 mL/min calculated using the following formula: GFR = 175 x Serum&#xD;
             Cr-1.154 x age-0.203 x 0.742 (female) and x 1.212 (if patient is African American).&#xD;
&#xD;
          -  Adequate liver function defined as AST, ALT ≤ 3 × upper limit of normal (UNL) in the&#xD;
             absence of liver metastasis and ≤ 5 × UNL with liver metastases; bilirubin &lt; 1.5 ×&#xD;
             UNL; alkaline phosphatase ≤ 2.5 × UNL in the absence of liver metastasis and &lt; 5 × UNL&#xD;
             in case of bone metastases.&#xD;
&#xD;
          -  TSH, T3 and free T4 must be within normal range.&#xD;
&#xD;
          -  The patient should not have had intravenous or intrathecal iodinated contrast agents&#xD;
             (IVP, CT with contrast, myelogram, angiogram) for 4 weeks prior to screening to their&#xD;
             124I- PET/CT scans and/or 131I- treatment.&#xD;
&#xD;
          -  Patients with treated brain metastases are eligible if the brain metastases have&#xD;
             remained stable for more than 4 weeks after completing therapy to the brain.&#xD;
&#xD;
          -  Normal urine or serum Beta-HCG in premenopausal women of childbearing potential&#xD;
&#xD;
          -  Women of childbearing potential must agree to use effective contraception during the&#xD;
             treatment period and for at least 6 months after the last dose of 124I- and/or 131I-&#xD;
             as these agents interfere with radioactive iodide uptake&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concurrent anti-tumor treatment including radiation therapy, hormonal and&#xD;
             chemotherapy.&#xD;
&#xD;
          -  Patients with symptomatic cardiac disease such as coronary artery disease, congestive&#xD;
             heart failure, or atrial fibrillation.&#xD;
&#xD;
          -  Significant gastrointestinal abnormalities, including: ulcerative colitis, chronic&#xD;
             diarrhea associated with intestinal malabsorption, Crohn's disease, and prior surgical&#xD;
             procedures affecting absorption.&#xD;
&#xD;
          -  Women who are nursing or pregnant.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lajos Pusztai, M.D., D.Phil</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University: Professor of Medicine, Section of Medical Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Smilow Cancer Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>December 7, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <last_update_submitted>August 20, 2018</last_update_submitted>
  <last_update_submitted_qc>August 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Metastatic Breast Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</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/NCT02988648
org study id: 1607018035
nct id: NCT02988648
lead sponsor: 
has dmc: Yes
The purpose of this phase I/II study is to evaluate the safety and clinical activity of
      Radioiodide (131I-) as a novel targeted therapy for metastatic breast cancer that
      overexpresses functional Na/I symporter. The study will enroll patients with metastatic
      breast cancer who have had clinical and/or radiographic evidence of disease progression on
      prior hormonal and/or chemotherapy.
The primary objectives of the study are as follows:

        1. To evaluate the feasibility of using 124I- PET/CT scans to identify patients whose
           metastatic lesions accumulate radioactive iodide and therefore are candidates for 131I-
           therapy.

        2. Determine the frequency of iodide (124I) enriching metastatic breast cancer.

        3. Evaluate the safety and clinical activity of one-time 131I treatment to patients who
           screen positive on 124I- PET/CT screening, positivity is defined as calculated iodide
           enrichment that will allow delivering 2000 cGy or more radiation to one or more
           metastatic lesion by administering up to 200mCi 131I-.

      The secondary objectives of the study are as follows:

      1. To investigate a correlation between NIS expression in tumor tissue with 124I- uptake on
      screening PET/CT scan

      The Phase I portion will follow a 3+3 design with 4 dose levels (30, 60, 120, and 200 mCi) of
      I- treatment. The maximum tolerated dose will be used in the Phase II efficacy assessment
      which will follow a Simon's optimal two-stage design. The primary efficacy measure is
      objective tumor response rate (CR or PR) with targeted activity level of > 20% response rate.

      The study will be terminated for futility if no tumor response is seen in the first 12
      patients. If futility criteria is not met, a total of 37 eligible patients will be enrolled
      in the Phase II portion. If 4 or more responses are seen after 37 patients were evaluated,
      then the investigators will conclude that the regimen warrants further study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: objective tumor response rate
time frame: Up to 24 weeks
description: The primary efficacy measure is objective tumor response rate (CR or PR) with targeted activity level of > 20% response rate.
Patients should be followed regularly until disease progression and until resolution of all acute toxicities associated with treatment administration. If stable disease or resolution of toxicities takes longer than 24 weeks, follow up frequency will be determined by the treating physician.
arm group label: radioiodide (I-)
arm group type: Experimental
description: The Phase I portion will follow a 3+3 design with 4 dose levels (30, 60, 120, and 200 mCi) of I- treatment. The maximum tolerated dose (from Phase I) will be used in the Phase II efficacy assessment which will follow a Simon's optimal two-stage design.
intervention type: Radiation
intervention name: Radioiodide (131I-)
description: The Phase I portion will follow a 3+3 design with 4 dose levels (30, 60, 120, and 200 mCi) of I- treatment. The maximum tolerated dose (from Phase I) will be used in the Phase II efficacy assessment which will follow a Simon's optimal two-stage design.
arm group label: radioiodide (I-)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Lajos Pusztai, M.D., D.Phil
role: Principal Investigator
affiliation: Yale University: Professor of Medicine, Section of Medical Oncology
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms