<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/NCT01730612</url>
  </required_header>
  <id_info>
    <org_study_id>BRD/10/04-O</org_study_id>
    <nct_id>NCT01730612</nct_id>
  </id_info>
  <brief_title>ImmunoTEP au 68-Ga- IMP-288 for Patients With a Recurrence of HER2 Negative Breast Carcinoma Expressing CEA</brief_title>
  <acronym>iTEPsein</acronym>
  <official_title>Pilot Study for Optimization of Immuno-PET Pretargeted With Anti-CEA Bispecific Antibody X Anti-HSG TF2 and the Peptide IMP-288 Radiolabeled With Gallium-68 -Pharmacokinetic and Imaging for Patients With a Recurrence of HER2 Negative Breast Carcinoma Expressing CEA</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nantes University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Gilead Sciences</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Nantes University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Main objective: To determine the optimal molar doses of the biospecific antibody TF2 and 68&#xD;
      Ga-IMP-288 and the optimal time for pretargeting for immuno-PET in patients with breast&#xD;
      carcinoma.&#xD;
&#xD;
      Secondary objectives: To study the sensitivity of the immuno-PET, compare its performance to&#xD;
      standard imaging methods, evaluate the safety of 150 MBq of 68 Ga-IMP-288; study the&#xD;
      development of immunization against TF2 or complex TF2-IMP-288;&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  4 or 5 cohorts of 3 patients receiving different doses of TF2 IMP-288 with different&#xD;
           interval time. A last cohort (4 or 5 ): maximum of 21 additional patients with the&#xD;
           optimal schedule.&#xD;
&#xD;
      Cohort I: TF2 120 nmol / 6 nmol IMP-288 / 24 hours&#xD;
&#xD;
      Cohort II: based on the results of the cohort I :&#xD;
&#xD;
        1. Good signal of the tumor but high background: increased interval time, 120 nmol TF2 / 6&#xD;
           nmol of IMP-288 / 30 hours&#xD;
&#xD;
        2. Low signal of the tumor: reduction of the interval time, 120 nmol TF2 / 6 nmol IMP-288 /&#xD;
           18 hours&#xD;
&#xD;
        3. Good signal of the tumor and good background signal : dose reduction, 60 nmol TF2 /&#xD;
           3nmol IMP- 288 / 24 hours&#xD;
&#xD;
           Cohort III: based on results of cohort II:&#xD;
&#xD;
           - Good signal of the tumor : dose reduction, 120 nmol TF2 / 3 nmol IMP-288 / 30 h&#xD;
&#xD;
           Cohort IV : based on results of cohort III Cohort V : Based on results of cohort IV&#xD;
&#xD;
           • A last Cohort (VI) : 19 patients with the optimal schedule of injection : 120 nmol TF2&#xD;
           / 3 nmol IMP-288 / 30 h or 120 nmol TF2 / 6 nmol IMP-288 / 30 h&#xD;
&#xD;
           • In the four weeks prior to the immuno-PET:&#xD;
&#xD;
           - Clinical examination,&#xD;
&#xD;
           - CEA and CA15-3,&#xD;
&#xD;
           - thoraco abdominal pelvic scan, bone scan, FDG-PET,&#xD;
&#xD;
           - immunohistochemistry ACE on the tumor if possible,&#xD;
&#xD;
           - Anti-Antibodies if the patient has already received MAb,&#xD;
&#xD;
           - pregnancy test within 2 days prior to immuno-PET,&#xD;
&#xD;
           - (creatinine &gt; 2.5 normal) D0: Injection of TF2 D1 to D4: injection of 68 Ga-IMP-288&#xD;
           (depending of the cohort) D0 to D4 : pharmacokinetics, imaging&#xD;
&#xD;
           Evaluation at 1 month of Immuno-PET:&#xD;
&#xD;
           • Assessment of the clinical oncologist and&#xD;
&#xD;
           - histological biopsy and / or surgery performed according to the results of imaging and&#xD;
           assessment of the potential clinical impact&#xD;
&#xD;
           Evaluation at 3 and 6 months of immuno-PET:&#xD;
&#xD;
           based on the results of immuno-PET, evaluation and therapeutic decision of the&#xD;
           oncologist,&#xD;
&#xD;
           - Imaging (ultrasound, bone scintigraphy, CT or PET FDG),&#xD;
&#xD;
           - markers&#xD;
&#xD;
             -  Anti-Antibody Search&#xD;
&#xD;
             -  For patient with a cancer treatment a new immuno-PET can be proposed&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">May 2017</completion_date>
  <primary_completion_date type="Actual">May 2017</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>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>evaluation of the tumor targeting (no Unit) and signal / noise ratio (no unit) by the immunoTEP with TF2 and 68-Ga-IMP-288</measure>
    <time_frame>One week</time_frame>
    <description>Pk blood after injections of TF2 and 68 Ga-IMP-288 and PET imaging semi-quantification with 60 to 120 minutes after injection of 68 Ga-IMP-288</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sensibility, tolerance</measure>
    <time_frame>6 months after immunoTEP</time_frame>
    <description>sensitivity of the immuno-PET and compare its performance to standard imaging methods, pathological data if available data or imaging follow-up of at least 6 months by RECIST and EORTC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To study the contribution of immnoTEP to assess early response to treatment, compare its performance to standard imaging methods</measure>
    <time_frame>month 6</time_frame>
    <description>6 weeks after initiation of treatment of metastases (after the first iTEP), a second _iTEP with a therapeutic evaluation will be carried out. The examination requirements are identical to those of the first immunoTEP.&#xD;
this second iITEP will be evaluated in regard of imaging assessment performed routinely (TAP scanner, FDG-PET, CA15-3 and CEA)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>• To assess the tolerance of 150 MBq of 68 Ga-IMP-288</measure>
    <time_frame>6 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>To search for the development of immunization with TF2 and the complex TF2-IMP-288: ELISA</measure>
    <time_frame>6 months</time_frame>
  </other_outcome>
  <enrollment type="Actual">23</enrollment>
  <condition>HER2 Negative Breast Carcinoma Expressing CEA</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TF2 - 68 Ga-IMP-288:</intervention_name>
    <description>ImmunoTEP</description>
    <other_name>TF2: trivalent recombinant humanized antibody recognizing the ACE and the peptide histamine-succinyl-glycine IMP-288 (HSG)</other_name>
    <other_name>68 Ga-IMP-288: di-HSG peptide-DOTA-labeled with Gallium 68</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Breast carcinoma, HER2 + (Dako) and HER2 + (fish) metastatic at least after treatment&#xD;
             with current consensus&#xD;
&#xD;
          -  ≥ 18 years&#xD;
&#xD;
          -  Negative pregnancy test for women of childbearing age. Women of childbearing age&#xD;
             should take effective contraception continuously for 3 months.&#xD;
&#xD;
          -  Karnofsky ≥ 70 or ECOG 0-1&#xD;
&#xD;
             •• ACE of the tumor by immunohistochemistry or positive plasma CEA ≥ 10 ng / mL&#xD;
&#xD;
          -  At least one measurable lesion on CT&#xD;
&#xD;
          -  creatinine &lt; 2.5&#xD;
&#xD;
          -  Informed consent signed&#xD;
&#xD;
          -  Social insurance&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
               -  Serious illness or co-morbidity risk assessed&#xD;
&#xD;
               -  History of cancer within 5 years except skin cancer other than melanoma or&#xD;
                  carcinoma in situ of the cervix&#xD;
&#xD;
               -  Presence of anti-antibodies in patients who have previously received antibodies&#xD;
&#xD;
               -  Known hypersensitivity to antibodies or proteins&#xD;
&#xD;
               -  intellectual disability to sign the informed consent&#xD;
&#xD;
               -  Not controlled diabetes&#xD;
&#xD;
               -  Persons protected by law&#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>francoise Bodere, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nantes Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de l'Ouest</name>
      <address>
        <city>Saint Herblain</city>
        <zip>44805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>November 12, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>July 26, 2018</last_update_submitted>
  <last_update_submitted_qc>July 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ImmunoTEP</keyword>
  <keyword>HER2 negative</keyword>
  <keyword>Breast Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Histamine</mesh_term>
    <mesh_term>Glycine</mesh_term>
  </intervention_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/NCT01730612
org study id: BRD/10/04-O
nct id: NCT01730612
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Main objective: To determine the optimal molar doses of the biospecific antibody TF2 and 68
      Ga-IMP-288 and the optimal time for pretargeting for immuno-PET in patients with breast
      carcinoma.

      Secondary objectives: To study the sensitivity of the immuno-PET, compare its performance to
      standard imaging methods, evaluate the safety of 150 MBq of 68 Ga-IMP-288; study the
      development of immunization against TF2 or complex TF2-IMP-288;
-  4 or 5 cohorts of 3 patients receiving different doses of TF2 IMP-288 with different
           interval time. A last cohort (4 or 5 ): maximum of 21 additional patients with the
           optimal schedule.

      Cohort I: TF2 120 nmol / 6 nmol IMP-288 / 24 hours

      Cohort II: based on the results of the cohort I :

        1. Good signal of the tumor but high background: increased interval time, 120 nmol TF2 / 6
           nmol of IMP-288 / 30 hours

        2. Low signal of the tumor: reduction of the interval time, 120 nmol TF2 / 6 nmol IMP-288 /
           18 hours

        3. Good signal of the tumor and good background signal : dose reduction, 60 nmol TF2 /
           3nmol IMP- 288 / 24 hours

           Cohort III: based on results of cohort II:

           - Good signal of the tumor : dose reduction, 120 nmol TF2 / 3 nmol IMP-288 / 30 h

           Cohort IV : based on results of cohort III Cohort V : Based on results of cohort IV

           • A last Cohort (VI) : 19 patients with the optimal schedule of injection : 120 nmol TF2
           / 3 nmol IMP-288 / 30 h or 120 nmol TF2 / 6 nmol IMP-288 / 30 h

           • In the four weeks prior to the immuno-PET:

           - Clinical examination,

           - CEA and CA15-3,

           - thoraco abdominal pelvic scan, bone scan, FDG-PET,

           - immunohistochemistry ACE on the tumor if possible,

           - Anti-Antibodies if the patient has already received MAb,

           - pregnancy test within 2 days prior to immuno-PET,

           - (creatinine > 2.5 normal) D0: Injection of TF2 D1 to D4: injection of 68 Ga-IMP-288
           (depending of the cohort) D0 to D4 : pharmacokinetics, imaging

           Evaluation at 1 month of Immuno-PET:

           • Assessment of the clinical oncologist and

           - histological biopsy and / or surgery performed according to the results of imaging and
           assessment of the potential clinical impact

           Evaluation at 3 and 6 months of immuno-PET:

           based on the results of immuno-PET, evaluation and therapeutic decision of the
           oncologist,

           - Imaging (ultrasound, bone scintigraphy, CT or PET FDG),

           - markers

             -  Anti-Antibody Search

             -  For patient with a cancer treatment a new immuno-PET can be proposed
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: evaluation of the tumor targeting (no Unit) and signal / noise ratio (no unit) by the immunoTEP with TF2 and 68-Ga-IMP-288
time frame: One week
description: Pk blood after injections of TF2 and 68 Ga-IMP-288 and PET imaging semi-quantification with 60 to 120 minutes after injection of 68 Ga-IMP-288
measure: Sensibility, tolerance
time frame: 6 months after immunoTEP
description: sensitivity of the immuno-PET and compare its performance to standard imaging methods, pathological data if available data or imaging follow-up of at least 6 months by RECIST and EORTC
measure: To study the contribution of immnoTEP to assess early response to treatment, compare its performance to standard imaging methods
time frame: month 6
description: 6 weeks after initiation of treatment of metastases (after the first iTEP), a second _iTEP with a therapeutic evaluation will be carried out. The examination requirements are identical to those of the first immunoTEP.
this second iITEP will be evaluated in regard of imaging assessment performed routinely (TAP scanner, FDG-PET, CA15-3 and CEA)
measure: • To assess the tolerance of 150 MBq of 68 Ga-IMP-288
time frame: 6 months
measure: To search for the development of immunization with TF2 and the complex TF2-IMP-288: ELISA
time frame: 6 months
intervention type: Drug
intervention name: TF2 - 68 Ga-IMP-288:
description: ImmunoTEP
other name: TF2: trivalent recombinant humanized antibody recognizing the ACE and the peptide histamine-succinyl-glycine IMP-288 (HSG)
other name: 68 Ga-IMP-288: di-HSG peptide-DOTA-labeled with Gallium 68
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: francoise Bodere, PhD, MD
role: Principal Investigator
affiliation: Nantes Hospital
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Breast Neoplasms
mesh term: Recurrence
mesh term: Histamine
mesh term: Glycine