<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/NCT03012789</url>
  </required_header>
  <id_info>
    <org_study_id>Surgery_NETest</org_study_id>
    <nct_id>NCT03012789</nct_id>
  </id_info>
  <brief_title>Surgical Intervention and the NETest</brief_title>
  <acronym>NETest_Sx</acronym>
  <official_title>Diagnosis of Neuroendocrine Neoplasms and Assessment of Response to Surgery by Means of Measurement of Gene Transcripts in Blood</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wren Laboratories LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wren Laboratories LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effect of different surgical resections (R0, R1,&#xD;
      R2) on circulating NET transcripts (PCR score or NETest). A drop in circulating NET levels&#xD;
      will be correlated with surgical excision. Secondly, variation of circulating NET transcripts&#xD;
      will be correlated to NET recurrence to test whether this analysis may constitute an early&#xD;
      predictive marker of disease relapse.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Biomarker-based tools that can accurately predict gastroenteropancreatic neuroendocrine tumor&#xD;
      (GEP-NET) treatment response and tumor recurrence are currently not available. Circulating&#xD;
      biomarkers that are associated with GEP-NETs are limited to measurements of plasma&#xD;
      chromogranin A (CgA). The investigators have developed a PCR-based tool to quantitate (score)&#xD;
      the circulating GEP-NET molecular signature (&quot;liquid&quot; biopsy) with high sensitivity and&#xD;
      specificity. This signature can identify all types of GEP-NETs including small (1cm)&#xD;
      non-metastatic tumors, is significantly reduced after tumor debulking and is decreased&#xD;
      following surgical &quot;cure&quot;. Elevated post-surgical scores are associated with tumor recurrence&#xD;
      within 6 months in ~40% of cases. Current NET treatment protocols are associated with tumor&#xD;
      recurrence (progression free survival) ranging from 5-18 months. The majority of patients&#xD;
      will experience a relapse within 18 months irrespective of the treatment approach. The&#xD;
      investigators hypothesize that a PCR measurement of circulating NET mRNA can accurately&#xD;
      predict the extent of surgical resection (tumor removal) and elevated scores can predict&#xD;
      tumor relapse before this occurs. This biomarker protocol seeks to test this hypothesis and&#xD;
      evaluate whether changes in plasma CgA are as effective in predicting resection and&#xD;
      recurrence.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 15, 2017</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>N/A</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>Biomarker prediction of tumor recurrence</measure>
    <time_frame>24 months</time_frame>
    <description>Analysis of the alterations in the biomarker levels (from post-surgical levels, i.e., month 1) will be utilized to establish when the disease status has altered; a sustained increase in score will be recorded and compared with imaging to assess whether this is associated with disease progression/recurrence.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biomarkers and clinical symptomatology</measure>
    <time_frame>24 months</time_frame>
    <description>Biomarker scores will be compared to the frequency of clinical symptoms, specifically flushing, to assess whether there is a relationship.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers and clinical symptomatology</measure>
    <time_frame>24 months</time_frame>
    <description>Biomarker scores will be compared to the frequency of clinical symptoms, specifically diarrhea, to assess whether there is a relationship.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Alteration in biomarkers and tumor removal</measure>
    <time_frame>24 months</time_frame>
    <description>Analysis of the change in biomarker scores (from baseline to post-surgical levels at 1 month) will be utilized to establish the strength of the relationship between the biomarker and volume of tumor removed (cm3).</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Neuroendocrine Tumor</condition>
  <condition>Gastroenteropancreatic</condition>
  <arm_group>
    <arm_group_label>Post Surgery</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgery</intervention_name>
    <description>Surgical excision</description>
    <arm_group_label>Post Surgery</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically confirmed, well differentiated (G1, G2 or G3), local and advanced&#xD;
             (metastatic), neuroendocrine tumor of gastro-enteropancreatic origin.&#xD;
&#xD;
          -  Treatment-naïve as well as patients who have received previous therapies.&#xD;
&#xD;
          -  Patients currently on LAR with clinically stable disease.&#xD;
&#xD;
          -  CT or MRI documentation of disease.&#xD;
&#xD;
          -  WHO performance status ≤2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known history of HIV seropositivity&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>San Raffaele Hospital IRCCS</name>
      <address>
        <city>Milano</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <results_reference>
    <citation>Modlin IM, Frilling A, Salem RR, Alaimo D, Drymousis P, Wasan HS, Callahan S, Faiz O, Weng L, Teixeira N, Bodei L, Drozdov I, Kidd M. Blood measurement of neuroendocrine gene transcripts defines the effectiveness of operative resection and ablation strategies. Surgery. 2016 Jan;159(1):336-47. doi: 10.1016/j.surg.2015.06.056. Epub 2015 Oct 9.</citation>
    <PMID>26456125</PMID>
  </results_reference>
  <results_reference>
    <citation>Modlin IM, Kidd M, Bodei L, Drozdov I, Aslanian H. The clinical utility of a novel blood-based multi-transcriptome assay for the diagnosis of neuroendocrine tumors of the gastrointestinal tract. Am J Gastroenterol. 2015 Aug;110(8):1223-32. doi: 10.1038/ajg.2015.160. Epub 2015 Jun 2.</citation>
    <PMID>26032155</PMID>
  </results_reference>
  <results_reference>
    <citation>Oberg K, Modlin IM, De Herder W, Pavel M, Klimstra D, Frilling A, Metz DC, Heaney A, Kwekkeboom D, Strosberg J, Meyer T, Moss SF, Washington K, Wolin E, Liu E, Goldenring J. Consensus on biomarkers for neuroendocrine tumour disease. Lancet Oncol. 2015 Sep;16(9):e435-e446. doi: 10.1016/S1470-2045(15)00186-2.</citation>
    <PMID>26370353</PMID>
  </results_reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>May 5, 2022</last_update_submitted>
  <last_update_submitted_qc>May 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 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>Neuroendocrine Tumors</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/NCT03012789
org study id: Surgery_NETest
nct id: NCT03012789
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the effect of different surgical resections (R0, R1,
      R2) on circulating NET transcripts (PCR score or NETest). A drop in circulating NET levels
      will be correlated with surgical excision. Secondly, variation of circulating NET transcripts
      will be correlated to NET recurrence to test whether this analysis may constitute an early
      predictive marker of disease relapse.
Biomarker-based tools that can accurately predict gastroenteropancreatic neuroendocrine tumor
      (GEP-NET) treatment response and tumor recurrence are currently not available. Circulating
      biomarkers that are associated with GEP-NETs are limited to measurements of plasma
      chromogranin A (CgA). The investigators have developed a PCR-based tool to quantitate (score)
      the circulating GEP-NET molecular signature ("liquid" biopsy) with high sensitivity and
      specificity. This signature can identify all types of GEP-NETs including small (1cm)
      non-metastatic tumors, is significantly reduced after tumor debulking and is decreased
      following surgical "cure". Elevated post-surgical scores are associated with tumor recurrence
      within 6 months in ~40% of cases. Current NET treatment protocols are associated with tumor
      recurrence (progression free survival) ranging from 5-18 months. The majority of patients
      will experience a relapse within 18 months irrespective of the treatment approach. The
      investigators hypothesize that a PCR measurement of circulating NET mRNA can accurately
      predict the extent of surgical resection (tumor removal) and elevated scores can predict
      tumor relapse before this occurs. This biomarker protocol seeks to test this hypothesis and
      evaluate whether changes in plasma CgA are as effective in predicting resection and
      recurrence.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Biomarker prediction of tumor recurrence
time frame: 24 months
description: Analysis of the alterations in the biomarker levels (from post-surgical levels, i.e., month 1) will be utilized to establish when the disease status has altered; a sustained increase in score will be recorded and compared with imaging to assess whether this is associated with disease progression/recurrence.
measure: Biomarkers and clinical symptomatology
time frame: 24 months
description: Biomarker scores will be compared to the frequency of clinical symptoms, specifically flushing, to assess whether there is a relationship.
measure: Biomarkers and clinical symptomatology
time frame: 24 months
description: Biomarker scores will be compared to the frequency of clinical symptoms, specifically diarrhea, to assess whether there is a relationship.
measure: Alteration in biomarkers and tumor removal
time frame: 24 months
description: Analysis of the change in biomarker scores (from baseline to post-surgical levels at 1 month) will be utilized to establish the strength of the relationship between the biomarker and volume of tumor removed (cm3).
arm group label: Post Surgery
arm group type: Other
intervention type: Procedure
intervention name: Surgery
description: Surgical excision
arm group label: Post Surgery
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Italy
citation: Modlin IM, Frilling A, Salem RR, Alaimo D, Drymousis P, Wasan HS, Callahan S, Faiz O, Weng L, Teixeira N, Bodei L, Drozdov I, Kidd M. Blood measurement of neuroendocrine gene transcripts defines the effectiveness of operative resection and ablation strategies. Surgery. 2016 Jan;159(1):336-47. doi: 10.1016/j.surg.2015.06.056. Epub 2015 Oct 9.
PMID: 26456125
citation: Modlin IM, Kidd M, Bodei L, Drozdov I, Aslanian H. The clinical utility of a novel blood-based multi-transcriptome assay for the diagnosis of neuroendocrine tumors of the gastrointestinal tract. Am J Gastroenterol. 2015 Aug;110(8):1223-32. doi: 10.1038/ajg.2015.160. Epub 2015 Jun 2.
PMID: 26032155
citation: Oberg K, Modlin IM, De Herder W, Pavel M, Klimstra D, Frilling A, Metz DC, Heaney A, Kwekkeboom D, Strosberg J, Meyer T, Moss SF, Washington K, Wolin E, Liu E, Goldenring J. Consensus on biomarkers for neuroendocrine tumour disease. Lancet Oncol. 2015 Sep;16(9):e435-e446. doi: 10.1016/S1470-2045(15)00186-2.
PMID: 26370353
responsible party type: Sponsor
mesh term: Neuroendocrine Tumors