<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/NCT04485286</url>
  </required_header>
  <id_info>
    <org_study_id>2020P001899</org_study_id>
    <secondary_id>R44CA250771</secondary_id>
    <secondary_id>K08CA259626</secondary_id>
    <nct_id>NCT04485286</nct_id>
  </id_info>
  <brief_title>Evaluation of PET Probe [68Ga]CBP8 in the Detection of Radiation Induced Tissue Injury</brief_title>
  <official_title>Evaluation of PET Probe [68Ga]CBP8 in the Detection of Radiation Induced Tissue Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</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>
      The goal of this study is to investigate the efficacy of [68Ga]CBP8 to detect collagen&#xD;
      deposition in radiation induced tissue injury.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Detailed Description:&#xD;
&#xD;
      The investigators have developed [68Ga]CBP8, a gallium-68 labeled collagen binding PET&#xD;
      imaging probe, which selectively binds collagen type I. Collagen deposition is a pivotal&#xD;
      event in several human conditions including radiation induced lung injury and in response to&#xD;
      radiation therapy in pancreatic cancer. The investigator's studies in murine models of lung&#xD;
      injury including radiation induced lung injury showed that [68Ga]CBP8 binds collagen with&#xD;
      high affinity and has excellent pharmacological and pharmacokinetic profiles with high target&#xD;
      uptake and low retention in background tissues and organs. [68Ga]CBP8 was shown in a mouse&#xD;
      model to be effective for detecting lung fibrosis. [68Ga]CBP8 showed high specificity for&#xD;
      pulmonary fibrosis and high target:background ratios in diseased animals. In addition,&#xD;
      [68Ga]CBP8 could be used to monitor response to treatment. Ex vivo analysis of lung tissue&#xD;
      from patients with idiopathic pulmonary fibrosis (IPF) supported the animal findings.&#xD;
&#xD;
      The investigators have conducted preliminary studies in humans with IPF and demonstrated a&#xD;
      significant increase in [68Ga]CBP8 signal in subjects with IPF vs healthy controls.&#xD;
&#xD;
      The investigators thus aim to evaluate [68Ga]CBP8 in human subjects with radiation induced&#xD;
      lung injury and in patients undergoing radiation therapy for pancreatic cancer:&#xD;
&#xD;
      To establish the ability of [68Ga]CBP8-PET to detect radiation-induced fibrosis in lung or&#xD;
      pancreatic cancer patients through the course of disease development with repeated measures,&#xD;
      and correlate signal with standard measures of radiation induced tissue injury such as HRCT&#xD;
      or MRI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 19, 2020</start_date>
  <completion_date type="Anticipated">July 2027</completion_date>
  <primary_completion_date type="Anticipated">May 2027</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>
    <intervention_model_description>Eligible subjects planning on receiving radiation for lung cancer or pancreatic cancer will be enrolled to undergo imaging with the PET Probe [68Ga]CBP8.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ability of [68Ga]CBP8 to detect collagen deposition in areas of radiation injury.</measure>
    <time_frame>3-6 Months</time_frame>
    <description>Probe uptake will be measured in lung cancer or pancreatic cancer patients 1) prior to radiation therapy and 2) 3-6 months after radiation therapy. We expect [68Ga]CBP8 signal to be increased in post radiation measurements over pre-radiation measurements in areas of irradiated tissue. Furthermore we expect that these areas will go on to develop radiation fibrosis.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">72</enrollment>
  <condition>Lung Cancer</condition>
  <condition>Radiation Fibrosis</condition>
  <condition>Radiation Induced Lung Injury</condition>
  <condition>Pancreas Cancer</condition>
  <arm_group>
    <arm_group_label>Lung Cancer or Pancreatic Cancer Subjects Undergoing Radiation Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lung cancer or pancreatic cancer patients will receive [68Ga]CBP8 and undergo PET imaging 1) prior to radiation therapy and 2) 3-6 months after radiation therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[68Ga]CBP8</intervention_name>
    <description>Up to 15 mCi of [68Ga]CBP8 will be administered to each subject. Each subject will undergo baseline imaging prior to radiation and again 3-6 months after radiation therapy.</description>
    <arm_group_label>Lung Cancer or Pancreatic Cancer Subjects Undergoing Radiation Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for lung cancer subjects:&#xD;
&#xD;
          -  Eligible patients will be those harboring locally advanced clinical stage I-III NSCLC&#xD;
             who are not eligible for surgical resection, or those with stage IIIa NSCLC who are&#xD;
             deemed candidates for multi-modality therapy, i.e. concurrent chemotherapy and&#xD;
             radiation followed by pulmonary resection.&#xD;
&#xD;
          -  Age greater than 18 years&#xD;
&#xD;
          -  Have the ability to give written informed consent.&#xD;
&#xD;
          -  No tobacco use within the prior 6 months.&#xD;
&#xD;
        Inclusion Criteria for pancreatic cancer subjects:&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Life expectancy of greater than 3 months.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
          -  Histologically or cytologically confirmed diagnosis of PDAC.&#xD;
&#xD;
          -  Tumor should be confirmed with imaging based on the standard-of-care baseline&#xD;
             abdominal CT performed within 1 month before study visit 1.&#xD;
&#xD;
          -  Core samples for initial diagnosis must be available at the Department of Pathology at&#xD;
             Massachusetts General Hospital.&#xD;
&#xD;
          -  Participants with a prior or concurrent malignancy whose natural history or treatment&#xD;
             does not have the potential to interfere with the safety or efficacy assessment of the&#xD;
             investigational imaging and standard treatment regimen are eligible for this trial.&#xD;
&#xD;
          -  Scheduled study visit 1 within 1 month prior to starting neoadjuvant chemoradiotherapy&#xD;
             (CRT)&#xD;
&#xD;
          -  Subjects undergo neoadjuvant chemotherapy followed by radiotherapy (CRT) as part of&#xD;
             their standard clinical care and based on institutional standards.&#xD;
&#xD;
          -  Scheduled surgical pancreas resection within 1 month after post-CRT study visit.&#xD;
&#xD;
          -  Subjects are required to undergo pre-surgical CT of abdomen within 1 month after&#xD;
             completion of standard neoadjuvant CRT as part of routine clinical work-up.&#xD;
&#xD;
        Exclusion Criteria for lung cancer subjects:&#xD;
&#xD;
          -  Electrical implants such as cardiac pacemaker or perfusion pump&#xD;
&#xD;
          -  Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial&#xD;
             hearts, valves with steel parts, metal fragments, shrapnel, metallic tattoos anywhere&#xD;
             on the body, tattoos near the eye, or steel implants ferromagnetic objects such as&#xD;
             jewelry or metal clips in clothing;&#xD;
&#xD;
          -  Pregnant or breastfeeding (a negative quantitative serum hCG pregnancy test is&#xD;
             required for females having child-bearing potential before the subject can&#xD;
             participate);&#xD;
&#xD;
          -  Claustrophobic reactions;&#xD;
&#xD;
          -  Research-related radiation exposure exceeds current Radiology Department guidelines&#xD;
             (i.e. 50 mSv in the prior 12 months);&#xD;
&#xD;
          -  Unable to lie comfortably on a bed inside the MR-PET;&#xD;
&#xD;
          -  Body weight of &gt; 300 lbs (weight limit of the MRI table);&#xD;
&#xD;
          -  Determined by the investigator(s) to be clinically unsuitable for the study (e.g.&#xD;
             based on screening visit and/or during study procedures);&#xD;
&#xD;
          -  Known history of pulmonary disease (Except lung cancer or smoking related lung&#xD;
             disease,)&#xD;
&#xD;
          -  Pneumonia or other acute respiratory illness within 6 weeks of study entry, pneumonia&#xD;
             defined with elevated WBC, fever, infiltrate on CXR and need for antibiotics&#xD;
&#xD;
        Exclusion Criteria for pancreatic cancer subjects:&#xD;
&#xD;
          -  History of radiotherapy to the upper abdomen in the past.&#xD;
&#xD;
          -  History of reaction to MRI contrast (Gadoterate meglumine)&#xD;
&#xD;
          -  Clinical or imaging diagnosis of acute pancreatitis within 6 weeks prior to study&#xD;
             visit&#xD;
&#xD;
          -  Participants with uncontrolled intercurrent illness or if determined by the&#xD;
             investigator(s) to be clinically unsuitable for the study (e.g. based on screening&#xD;
             and/or during study).&#xD;
&#xD;
          -  Participants with psychiatric illness/social situations that would limit compliance&#xD;
             with study requirements.&#xD;
&#xD;
          -  Electrical implants such as cardiac pacemaker or perfusion pump;&#xD;
&#xD;
          -  Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial&#xD;
             hearts, valves with steel parts, metal fragments, shrapnel, metallic tattoos anywhere&#xD;
             on the body, tattoos near the eye, or steel implants ferromagnetic objects such as&#xD;
             jewelry or metal clips in clothing;&#xD;
&#xD;
          -  eGFR of less than 30 mL/min/1.73 m2 within the past 90 days;&#xD;
&#xD;
          -  Pregnant or breastfeeding (a negative quantitative serum hCG pregnancy test is&#xD;
             required for females having child-bearing potential at each PET/MRI study visit;&#xD;
&#xD;
          -  Claustrophobic reactions;&#xD;
&#xD;
          -  Research-related radiation exposure exceeds current Radiology Department guidelines&#xD;
             (i.e. 50 mSv in the prior 12 months);&#xD;
&#xD;
          -  Unable to lie comfortably on a bed inside the MR-PET;&#xD;
&#xD;
          -  BMI &gt; 33 (limit of the PET-MRI table)&#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>Michael Lanuti, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Shadi Esfahani, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Michael Lanuti, MD</last_name>
    <phone>6176430193</phone>
    <email>mlanuti@mgh.harvard.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Shadi Esfahani, MD</last_name>
    <email>AbdarEsfahani.Shadi@mgh.harvard.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael Lanuti, MD</last_name>
      <phone>617-726-6751</phone>
      <email>MLANUTI@mgh.harvard.edu</email>
    </contact>
    <contact_backup>
      <last_name>Eric Abston, MD</last_name>
      <phone>920-286-3773</phone>
      <email>EABSTON@mgh.harvard.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Michael Lanuti, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Montesi SB, Izquierdo-Garcia D, Desogere P, Abston E, Liang LL, Digumarthy S, Seethamraju R, Lanuti M, Caravan P, Catana C. Type I Collagen-targeted Positron Emission Tomography Imaging in Idiopathic Pulmonary Fibrosis: First-in-Human Studies. Am J Respir Crit Care Med. 2019 Jul 15;200(2):258-261. doi: 10.1164/rccm.201903-0503LE. No abstract available.</citation>
    <PMID>31161770</PMID>
  </reference>
  <reference>
    <citation>Desogere P, Tapias LF, Rietz TA, Rotile N, Blasi F, Day H, Elliott J, Fuchs BC, Lanuti M, Caravan P. Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. J Nucl Med. 2017 Dec;58(12):1991-1996. doi: 10.2967/jnumed.117.193532. Epub 2017 Jun 13.</citation>
    <PMID>28611243</PMID>
  </reference>
  <reference>
    <citation>Desogere P, Tapias LF, Hariri LP, Rotile NJ, Rietz TA, Probst CK, Blasi F, Day H, Mino-Kenudson M, Weinreb P, Violette SM, Fuchs BC, Tager AM, Lanuti M, Caravan P. Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Sci Transl Med. 2017 Apr 5;9(384):eaaf4696. doi: 10.1126/scitranslmed.aaf4696.</citation>
    <PMID>28381537</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>April 30, 2023</last_update_submitted>
  <last_update_submitted_qc>April 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Peter Caravan</investigator_full_name>
    <investigator_title>Professor of Radiology</investigator_title>
  </responsible_party>
  <keyword>fibrosis</keyword>
  <keyword>positron emission tomography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Lung Injury</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
    <mesh_term>Radiation Fibrosis Syndrome</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <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/NCT04485286
org study id: 2020P001899
secondary id: R44CA250771
secondary id: K08CA259626
nct id: NCT04485286
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The goal of this study is to investigate the efficacy of [68Ga]CBP8 to detect collagen
      deposition in radiation induced tissue injury.
Detailed Description:

      The investigators have developed [68Ga]CBP8, a gallium-68 labeled collagen binding PET
      imaging probe, which selectively binds collagen type I. Collagen deposition is a pivotal
      event in several human conditions including radiation induced lung injury and in response to
      radiation therapy in pancreatic cancer. The investigator's studies in murine models of lung
      injury including radiation induced lung injury showed that [68Ga]CBP8 binds collagen with
      high affinity and has excellent pharmacological and pharmacokinetic profiles with high target
      uptake and low retention in background tissues and organs. [68Ga]CBP8 was shown in a mouse
      model to be effective for detecting lung fibrosis. [68Ga]CBP8 showed high specificity for
      pulmonary fibrosis and high target:background ratios in diseased animals. In addition,
      [68Ga]CBP8 could be used to monitor response to treatment. Ex vivo analysis of lung tissue
      from patients with idiopathic pulmonary fibrosis (IPF) supported the animal findings.

      The investigators have conducted preliminary studies in humans with IPF and demonstrated a
      significant increase in [68Ga]CBP8 signal in subjects with IPF vs healthy controls.

      The investigators thus aim to evaluate [68Ga]CBP8 in human subjects with radiation induced
      lung injury and in patients undergoing radiation therapy for pancreatic cancer:

      To establish the ability of [68Ga]CBP8-PET to detect radiation-induced fibrosis in lung or
      pancreatic cancer patients through the course of disease development with repeated measures,
      and correlate signal with standard measures of radiation induced tissue injury such as HRCT
      or MRI.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Eligible subjects planning on receiving radiation for lung cancer or pancreatic cancer will be enrolled to undergo imaging with the PET Probe [68Ga]CBP8.
primary purpose: Diagnostic
masking: None (Open Label)
measure: Ability of [68Ga]CBP8 to detect collagen deposition in areas of radiation injury.
time frame: 3-6 Months
description: Probe uptake will be measured in lung cancer or pancreatic cancer patients 1) prior to radiation therapy and 2) 3-6 months after radiation therapy. We expect [68Ga]CBP8 signal to be increased in post radiation measurements over pre-radiation measurements in areas of irradiated tissue. Furthermore we expect that these areas will go on to develop radiation fibrosis.
arm group label: Lung Cancer or Pancreatic Cancer Subjects Undergoing Radiation Therapy
arm group type: Experimental
description: Lung cancer or pancreatic cancer patients will receive [68Ga]CBP8 and undergo PET imaging 1) prior to radiation therapy and 2) 3-6 months after radiation therapy
intervention type: Drug
intervention name: [68Ga]CBP8
description: Up to 15 mCi of [68Ga]CBP8 will be administered to each subject. Each subject will undergo baseline imaging prior to radiation and again 3-6 months after radiation therapy.
arm group label: Lung Cancer or Pancreatic Cancer Subjects Undergoing Radiation Therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Michael Lanuti, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
last name: Shadi Esfahani, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
last name: Michael Lanuti, MD
phone: 6176430193
email: mlanuti@mgh.harvard.edu
last name: Shadi Esfahani, MD
email: AbdarEsfahani.Shadi@mgh.harvard.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
citation: Montesi SB, Izquierdo-Garcia D, Desogere P, Abston E, Liang LL, Digumarthy S, Seethamraju R, Lanuti M, Caravan P, Catana C. Type I Collagen-targeted Positron Emission Tomography Imaging in Idiopathic Pulmonary Fibrosis: First-in-Human Studies. Am J Respir Crit Care Med. 2019 Jul 15;200(2):258-261. doi: 10.1164/rccm.201903-0503LE. No abstract available.
PMID: 31161770
citation: Desogere P, Tapias LF, Rietz TA, Rotile N, Blasi F, Day H, Elliott J, Fuchs BC, Lanuti M, Caravan P. Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. J Nucl Med. 2017 Dec;58(12):1991-1996. doi: 10.2967/jnumed.117.193532. Epub 2017 Jun 13.
PMID: 28611243
citation: Desogere P, Tapias LF, Hariri LP, Rotile NJ, Rietz TA, Probst CK, Blasi F, Day H, Mino-Kenudson M, Weinreb P, Violette SM, Fuchs BC, Tager AM, Lanuti M, Caravan P. Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Sci Transl Med. 2017 Apr 5;9(384):eaaf4696. doi: 10.1126/scitranslmed.aaf4696.
PMID: 28381537
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Peter Caravan
investigator title: Professor of Radiology
mesh term: Pancreatic Neoplasms
mesh term: Lung Injury
mesh term: Fibrosis
mesh term: Radiation Fibrosis Syndrome
mesh term: Wounds and Injuries
sharing ipd: No