<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/NCT04469127</url>
  </required_header>
  <id_info>
    <org_study_id>145358</org_study_id>
    <nct_id>NCT04469127</nct_id>
  </id_info>
  <brief_title>A Phase I/II Multicenter, Open-Label Study of Lu-177-αvβ3-IAC, for the Treatment of Angiogenic Breast Cancer Patients.</brief_title>
  <acronym>Heroine01</acronym>
  <official_title>This Study is a Phase I/II Clinical Evaluation of a New Investigational Agent, Lutetium-177-PEG-αvβ3-IAC (HurlutinTM Lu-177) to Treat Patients With Unresectable Angiogenic Breast Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Advanced Imaging Projects, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>All India Institute of Medical Sciences, New Delhi</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Witwatersrand, South Africa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Postgraduate Institute of Medical and Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>US Department of Veterans Affairs</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Advanced Imaging Projects, LLC</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 study is a Phase I/II clinical evaluation of a new investigational agent,&#xD;
      Lutetium-177-DOTAGA-PEG-IAC (HurlutinTM Lu-177) to treat patients with unresectable&#xD;
      angiogenic breast cancer who have previously been treated with at least one prior line of&#xD;
      therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, Phase I/II multi-center, interventional open-label study in a total of&#xD;
      up to 100 subjects with angiogenic breast cancer. Phase I is to assess the safety and&#xD;
      adequacy of a dose of HurlutinTM Lu-177 for up to two cycles, at 6-8-week intervals. It will&#xD;
      include a dose expansion cohort of up to 20 patients. Phase II is to demonstrate the safety,&#xD;
      dose adequacy, anti-tumor activity and efficacy of tumor targeted therapy using&#xD;
      Lutetium-177-DOTAGA-PEG-IAC , as a second- or third-line treatment to extend survival and&#xD;
      improve the quality of life of patients with angiogenic breast cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">January 30, 2023</start_date>
  <completion_date type="Anticipated">August 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">August 30, 2024</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>Specific Aim 1</measure>
    <time_frame>6 months</time_frame>
    <description>To determine the safety and tolerability of fractionated administrations of 2 cycles of Lu-177-DOTAGA-PEG-IAC administered with 4 weeks between cycles in patients with high-risk Angiogenic Breast Cancer who have progressed on, or do not tolerate, best standard-of-care treatment.&#xD;
Measurements used to assess the safety, tolerability and side-effects profile will include adverse events of any grade, grade 3 and 4 adverse events, withdrawals due to adverse events and dose reductions due to adverse events. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v.5.0) will be used to evaluate AE grade.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Specific Aim 2</measure>
    <time_frame>6 months</time_frame>
    <description>To determine the pharmacokinetics (PK) of Lu-177-DOTAGA-PEG-IAC. The area under the Time vs. Concentration curve for Ga-68-αvβ3-IAC from injection to 72 h</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Specific Aim 3</measure>
    <time_frame>6 months</time_frame>
    <description>To determine the whole-body biodistribution of Lu-177-DOTAGA-PEG-IAC. Percent injected dose per gram of tissue (%ID)/gm of Lu-177-DOTAGA-PEG-IAC.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Specific Aim 4</measure>
    <time_frame>6 months</time_frame>
    <description>To determine the radiation dosimetry of Lu-177-DOTAGA-PEG-IAC.Time points will be 0 and 120, 30 and 150, 60 and 180, or 90 and 210 min after injection.Time integrals of activity will be entered into the (Organ Level INternal Dose Assessment/ EXponential Modeling) OLINDA/EXM software.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Specific Aims 5</measure>
    <time_frame>6 months</time_frame>
    <description>To determine optimum cumulative fractionated administered dose. Increase dose range if a DLT (Dose Limiting Toxicity) develops or they do not have a T/B ratio &gt;1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Specific Aim 1</measure>
    <time_frame>6-12 Months</time_frame>
    <description>To determine the Objective Response Rate (ORR) of fractionated administration of Lu-177-αvβ3-IAC.Percentage of subjects still alive. Percentage of subjects who achieved a best overall response of Complete Response [CR] or Partial Response [PR] according to RECIST 5.0 Criteria.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Breast Cancer Stage IV</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single Arm study Lu-177-DOTAGA-PEG-IAC (intracutaneous)&#xD;
Dosage and Dose Escalation Frequency:&#xD;
Cohort 1: 75 mCi x 3 (maximum cumulative administered activity, 225mCi) + 100 μgr IAC Cohort 2: 150 mCi x 3 (maximum cumulative administered activity, 450mCi) + 100 μgr IAC Cohort 3: 200 mCi x 3 (maximum cumulative administered activity, 600mCi) + 100 μgr IAC&#xD;
Three cycles each 8 weeks apart.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lutetium-177-DOTAGA-PEG-IAC</intervention_name>
    <description>Study participants be administered therapeutic doses of Lutetium-177-PEG-DOTAGA-PEG-IAC up to three treatments spaced 6-8 weeks apart and a CT scan immediately after. A Ga-68-PEG-αvβ3-IAC PET/CT scan will be performed four weeks before and four weeks after the initial dose of the Lutetium-177-DOTAGA-PEG-IAC.</description>
    <arm_group_label>Arm 1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Angiogenic breast tumor by immunohistochemistry confirmation.&#xD;
&#xD;
          2. Positive scan with PET/CT imaging with Ga-68 αvβ3-IAC PET/CT.&#xD;
&#xD;
          3. Tumor progression resistant or refractory to at least one prior lines of standard&#xD;
             chemotherapy which include trastuzumab and/or Ado-trastuzumab with or without&#xD;
             chemotherapy agents.&#xD;
&#xD;
          4. At least 18 years of age&#xD;
&#xD;
          5. The patient is able and willing to provide informed consent and to comply with the&#xD;
             requirements of this trial protocol.&#xD;
&#xD;
          6. ECOG score ≤3&#xD;
&#xD;
          7. Females of childbearing potential must have a negative serum pregnancy test or have&#xD;
             had an intervention that renders pregnancy not possible&#xD;
&#xD;
          8. Adequate organ function, defined as:&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/mL.&#xD;
&#xD;
               2. Hemoglobin (Hb) ≥10 g/dl (transfusion or use of EPO is permitted).&#xD;
&#xD;
               3. Platelets &gt; 100,000/mm3&#xD;
&#xD;
               4. Creatinine ≤ 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
               5. AST or ALT ≤ 2.5 x ULN (or ≤5 x ULN in case of liver metastasis)&#xD;
&#xD;
               6. Alkaline phosphatase ≤2.5 x ULN. Alkaline phosphatase may be more than 2.5 x ULN&#xD;
                  only in the case of bone metastases, and AST and ALT less than 1.5 x ULN.&#xD;
&#xD;
               7. Total bilirubin ≤1.5 mg/dl (higher bilirubin levels are permitted if the patient&#xD;
                  has Gilbert's syndrome).&#xD;
&#xD;
          9. Baseline LVEF ≥40% measured using echocardiogram or equilibrium isotopic&#xD;
             ventriculography&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previously received external beam irradiation that includes more than 30% of bone&#xD;
             marrow&#xD;
&#xD;
          2. Previously received external beam irradiation to a field that one kidney.&#xD;
&#xD;
          3. Previously received external beam irradiation to a field that includes the only known&#xD;
             lesion.&#xD;
&#xD;
          4. Any uncontrolled significant medical, psychiatric or surgical condition or laboratory&#xD;
             finding that would pose a risk to subject safety or interfere with study participation&#xD;
             or interpretation of individual subject results.&#xD;
&#xD;
          5. Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject&#xD;
             at high risk of renal toxicity during the study.&#xD;
&#xD;
          6. eGFR ≤ 50.&#xD;
&#xD;
          7. Bone metastases are the only known lesions.&#xD;
&#xD;
          8. Patients with a body weight of 400 pounds or more or not able to enter the bore of the&#xD;
             PET/CT scanner due to BMI, because of the compromise in image quality with CT, PET/CT&#xD;
             and MRI that will result.&#xD;
&#xD;
          9. Inability to lie still for the entire imaging time (e.g., cough, severe arthritis,&#xD;
             etc.).&#xD;
&#xD;
         10. Use of any other investigational therapeutic product within 30 days prior to dosing or&#xD;
             known requirement for any other investigational agent prior to completion of all&#xD;
             scheduled study assessments.&#xD;
&#xD;
         11. Recognized concurrent active infection.&#xD;
&#xD;
         12. Received any live (attenuated) vaccines within 30 days prior to Visit.&#xD;
&#xD;
         13. Recent or chronic treatment with medium-to-high-dose intravenous corticosteroids&#xD;
             (methylprednisolone 60 mg/day or hydrocortisone 300 mg/day) within 8 weeks prior to&#xD;
             Visit or oral corticosteroids of more than 20 mg prednisone (or equivalent) within 30&#xD;
             days prior to Visit&#xD;
&#xD;
         14. Any unresolved NCI-CTCAE Grade 2 or higher (except alopecia) from previous anti-tumour&#xD;
             treatment and/or medical/surgical procedures/interventions.&#xD;
&#xD;
         15. Additional inclusion criterion for measure human dosimetry&#xD;
&#xD;
               1. Unable to comply with the requirements of the dosimetry imaging protocol&#xD;
&#xD;
               2. Due to potential radiation safety issues, patients with urinary drainage or&#xD;
                  diversion (e.g., in-dwelling Foley™ catheter, ureteroileostomy, etc.) will not be&#xD;
                  enrolled.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stanley Satz, Ph.D.</last_name>
    <role>Study Director</role>
    <affiliation>Advanced Imaging Projects</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Stanley Satz, Ph.D.</last_name>
    <phone>561-561 286-6842</phone>
    <email>ssatz@advancedimagingprojects.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rose Satz</last_name>
    <phone>5617578666</phone>
    <email>rsatz@advancedimagingprojects.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Veterans Affairs</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>David L Bushnell, M.D.</last_name>
      <phone>319-384-7306</phone>
      <email>david-bushnell@uiowa.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>All India Institute of Medical Sciences</name>
      <address>
        <city>New Delhi</city>
        <state>Dehli</state>
        <zip>110029</zip>
        <country>India</country>
      </address>
    </facility>
    <contact>
      <last_name>C.S. Bal, M.D./Ph.D.</last_name>
      <email>drcsbal@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Postgraduate Institute of Medical and Research</name>
      <address>
        <city>Chandigarh</city>
        <zip>160 012</zip>
        <country>India</country>
      </address>
    </facility>
    <contact>
      <last_name>Br Mittal, M.D./Ph.D.</last_name>
      <phone>+911722756722</phone>
      <email>brmittal@yahoo.com</email>
    </contact>
  </location>
  <location_countries>
    <country>India</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Chile</country>
    <country>Italy</country>
    <country>South Africa</country>
    <country>Switzerland</country>
  </removed_countries>
  <results_reference>
    <citation>Baum RP, Kulkarni HR, Muller D, Satz S, Danthi N, Kim YS, Brechbiel MW. First-In-Human Study Demonstrating Tumor-Angiogenesis by PET/CT Imaging with (68)Ga-NODAGA-THERANOST, a High-Affinity Peptidomimetic for alphavbeta3 Integrin Receptor Targeting. Cancer Biother Radiopharm. 2015 May;30(4):152-9. doi: 10.1089/cbr.2014.1747.</citation>
    <PMID>25945808</PMID>
  </results_reference>
  <results_reference>
    <citation>Kim YS, Nwe K, Milenic DE, Brechbiel MW, Satz S, Baidoo KE. Synthesis and characterization of alphavbeta(3)-targeting peptidomimetic chelate conjugates for PET and SPECT imaging. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5517-22. doi: 10.1016/j.bmcl.2012.07.024. Epub 2012 Jul 14.</citation>
    <PMID>22853992</PMID>
  </results_reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>November 11, 2022</last_update_submitted>
  <last_update_submitted_qc>November 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 16, 2022</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>Breast Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD is to be shared with researchers</ipd_description>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>1 Yr.</ipd_time_frame>
    <ipd_access_criteria>Contact Sponsor</ipd_access_criteria>
  </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/NCT04469127
org study id: 145358
nct id: NCT04469127
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study is a Phase I/II clinical evaluation of a new investigational agent,
      Lutetium-177-DOTAGA-PEG-IAC (HurlutinTM Lu-177) to treat patients with unresectable
      angiogenic breast cancer who have previously been treated with at least one prior line of
      therapy.
This is a prospective, Phase I/II multi-center, interventional open-label study in a total of
      up to 100 subjects with angiogenic breast cancer. Phase I is to assess the safety and
      adequacy of a dose of HurlutinTM Lu-177 for up to two cycles, at 6-8-week intervals. It will
      include a dose expansion cohort of up to 20 patients. Phase II is to demonstrate the safety,
      dose adequacy, anti-tumor activity and efficacy of tumor targeted therapy using
      Lutetium-177-DOTAGA-PEG-IAC , as a second- or third-line treatment to extend survival and
      improve the quality of life of patients with angiogenic breast cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Specific Aim 1
time frame: 6 months
description: To determine the safety and tolerability of fractionated administrations of 2 cycles of Lu-177-DOTAGA-PEG-IAC administered with 4 weeks between cycles in patients with high-risk Angiogenic Breast Cancer who have progressed on, or do not tolerate, best standard-of-care treatment.
Measurements used to assess the safety, tolerability and side-effects profile will include adverse events of any grade, grade 3 and 4 adverse events, withdrawals due to adverse events and dose reductions due to adverse events. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v.5.0) will be used to evaluate AE grade.
measure: Specific Aim 2
time frame: 6 months
description: To determine the pharmacokinetics (PK) of Lu-177-DOTAGA-PEG-IAC. The area under the Time vs. Concentration curve for Ga-68-αvβ3-IAC from injection to 72 h
measure: Specific Aim 3
time frame: 6 months
description: To determine the whole-body biodistribution of Lu-177-DOTAGA-PEG-IAC. Percent injected dose per gram of tissue (%ID)/gm of Lu-177-DOTAGA-PEG-IAC.
measure: Specific Aim 4
time frame: 6 months
description: To determine the radiation dosimetry of Lu-177-DOTAGA-PEG-IAC.Time points will be 0 and 120, 30 and 150, 60 and 180, or 90 and 210 min after injection.Time integrals of activity will be entered into the (Organ Level INternal Dose Assessment/ EXponential Modeling) OLINDA/EXM software.
measure: Specific Aims 5
time frame: 6 months
description: To determine optimum cumulative fractionated administered dose. Increase dose range if a DLT (Dose Limiting Toxicity) develops or they do not have a T/B ratio >1.
measure: Specific Aim 1
time frame: 6-12 Months
description: To determine the Objective Response Rate (ORR) of fractionated administration of Lu-177-αvβ3-IAC.Percentage of subjects still alive. Percentage of subjects who achieved a best overall response of Complete Response [CR] or Partial Response [PR] according to RECIST 5.0 Criteria.
arm group label: Arm 1
arm group type: Experimental
description: Single Arm study Lu-177-DOTAGA-PEG-IAC (intracutaneous)
Dosage and Dose Escalation Frequency:
Cohort 1: 75 mCi x 3 (maximum cumulative administered activity, 225mCi) + 100 μgr IAC Cohort 2: 150 mCi x 3 (maximum cumulative administered activity, 450mCi) + 100 μgr IAC Cohort 3: 200 mCi x 3 (maximum cumulative administered activity, 600mCi) + 100 μgr IAC
Three cycles each 8 weeks apart.
intervention type: Drug
intervention name: Lutetium-177-DOTAGA-PEG-IAC
description: Study participants be administered therapeutic doses of Lutetium-177-PEG-DOTAGA-PEG-IAC up to three treatments spaced 6-8 weeks apart and a CT scan immediately after. A Ga-68-PEG-αvβ3-IAC PET/CT scan will be performed four weeks before and four weeks after the initial dose of the Lutetium-177-DOTAGA-PEG-IAC.
arm group label: Arm 1
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Stanley Satz, Ph.D.
role: Study Director
affiliation: Advanced Imaging Projects
last name: Stanley Satz, Ph.D.
phone: 561-561 286-6842
email: ssatz@advancedimagingprojects.com
last name: Rose Satz
phone: 5617578666
email: rsatz@advancedimagingprojects.com
facility: 
contact: 
facility: 
contact: 
facility: 
contact: 
country: India
country: United States
country: Chile
country: Italy
country: South Africa
country: Switzerland
citation: Baum RP, Kulkarni HR, Muller D, Satz S, Danthi N, Kim YS, Brechbiel MW. First-In-Human Study Demonstrating Tumor-Angiogenesis by PET/CT Imaging with (68)Ga-NODAGA-THERANOST, a High-Affinity Peptidomimetic for alphavbeta3 Integrin Receptor Targeting. Cancer Biother Radiopharm. 2015 May;30(4):152-9. doi: 10.1089/cbr.2014.1747.
PMID: 25945808
citation: Kim YS, Nwe K, Milenic DE, Brechbiel MW, Satz S, Baidoo KE. Synthesis and characterization of alphavbeta(3)-targeting peptidomimetic chelate conjugates for PET and SPECT imaging. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5517-22. doi: 10.1016/j.bmcl.2012.07.024. Epub 2012 Jul 14.
PMID: 22853992
responsible party type: Sponsor
mesh term: Breast Neoplasms
sharing ipd: Yes
ipd description: IPD is to be shared with researchers
ipd info type: Clinical Study Report (CSR)
ipd time frame: 1 Yr.
ipd access criteria: Contact Sponsor