<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/NCT03817866</url>
  </required_header>
  <id_info>
    <org_study_id>Brahms-CASPAR</org_study_id>
    <nct_id>NCT03817866</nct_id>
  </id_info>
  <brief_title>Chromogranin A as Blood Marker in Cancer Patients</brief_title>
  <official_title>Chromogranin A as Surveillance Biomarker in Patients With cARcinoids (The CASPAR Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brahms AG</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Brahms AG</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>
      Gastroentero-pancreatic neuroendocrine tumors (GEP-NETs) are a heterogenous group of&#xD;
      neoplasms that arise from enterochromaffin cells of the gastrointestinal (GI) tract and&#xD;
      pancreas. They account for 50-70% of all incident NETs. Due to the lack of symptoms in the&#xD;
      early stage of disease and the frequency of nonspecific GI symptoms, GEP-NETs are difficult&#xD;
      to diagnose.&#xD;
&#xD;
      Identification of effective biomarkers (such as Chromogranin A) to improve GEP-NET diagnosis,&#xD;
      as well as to assess treatment efficacy, relapse and prognosis, is important for improving&#xD;
      outcomes for patients with GEP-NETs.&#xD;
&#xD;
      The purpose of this study is to validate the performance of Brahms (BRAHMS) Chromogranin A II&#xD;
      Kryptor (KRYPTOR) assay to monitor the course of disease in patients with well-defined&#xD;
      GEP-NETs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A general characteristic for neuroendocrine tumors (NET) is expression of chromogranin A&#xD;
      (CgA), which is released from neuroendocrine cells, occasionally together with cell specific&#xD;
      hormones such as gastrin, insulin, somatostatin, and serotonin in functional tumors. Human&#xD;
      CgA is an acidic 439 amino acid protein with a sequence containing several mono- and dibasic&#xD;
      cleavage sites, and correspondingly, numerous fragments of CgA have been identified in tissue&#xD;
      and plasma. CgA is critical to the formation of secretory granules that characterize NETs,&#xD;
      and is therefore a useful marker for NETs.&#xD;
&#xD;
      Plasma concentrations of CgA and/or CgA fragments are elevated in most NETs. Moreover, since&#xD;
      plasma CgA concentrations seem to be closely related to tumor burden in humans, plasma CgA&#xD;
      concentration is an important prognostic factor. As such, high plasma concentrations of CgA&#xD;
      as well as a dramatic increase in plasma CgA within a short time period, is associated with a&#xD;
      poorer prognosis. Plasma CgA has also been suggested to be useful in the follow-up of&#xD;
      patients with NETs.&#xD;
&#xD;
      Taken together, these observations support the notion that CgA is a promising biomarker&#xD;
      candidate for monitoring treatment effectiveness and disease progression or regression.&#xD;
&#xD;
      Participation in this clinical study requires no additional visits to the oncologist,&#xD;
      radiology or the laboratory. All information needed for the study will be obtained during&#xD;
      typical visits as recommended by the oncologist. Clinical assessment of patients with&#xD;
      GEP-NETs (according to NCCN guidelines) is based on physical exam, imaging (CT or MRI scans)&#xD;
      and laboratory parameters. The course of disease is followed by RECIST 1.1 categorization&#xD;
      including the evaluation of tumor burden by imaging.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 29, 2019</start_date>
  <completion_date type="Actual">December 14, 2021</completion_date>
  <primary_completion_date type="Actual">December 14, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Disease Progression</measure>
    <time_frame>36 months</time_frame>
    <description>Progression vs. non-progression in patients with well-defined GEP-NETs assessed by RECIST 1.1 criteria</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">175</enrollment>
  <condition>Gastric Neoplasms</condition>
  <condition>Pancreatic Neoplasms</condition>
  <condition>Small Intestinal Neoplasms</condition>
  <condition>Colorectal Neoplasms</condition>
  <arm_group>
    <arm_group_label>BRAHMS CgA II KRYPTOR</arm_group_label>
    <description>Adult patients with well defined grade 1 and grade 2 GEP-NETs. Serial serum samples from all patients will be analyzed using the BRAHMS CgA II KRYPTOR Assay.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>BRAHMS CgA II KRYPTOR</intervention_name>
    <description>The BRAHMS CgA II KRYPTOR kit is an automated immunofluorescent assay for the quantitative determination of the concentration of CgA in human serum.&#xD;
The assay is to be used as an aid in monitoring disease progression during the course of disease and treatment in patients with GEP-NETs (grade 1 and grade 2).&#xD;
Serial testing for patient BRAHMS CgA II KRYPTOR assay values should be used in conjunction with other clinical methods for monitoring GEP-NETs (grade 1 and grade 2).</description>
    <arm_group_label>BRAHMS CgA II KRYPTOR</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients with diagnosed well-differentiated G1 and G2 GEP-NETs&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primary well-differentiated G1 and G2 neuroendocrine tumor located in jejunum, ileum,&#xD;
             colon, rectum, duodenum, appendix, stomach, or pancreas&#xD;
&#xD;
          -  Measurable disease according to RECIST criteria (Version 1.1)&#xD;
&#xD;
          -  Eighteen years of age or older&#xD;
&#xD;
          -  CT or MRI order obtained and within 4 weeks of CgA measurement&#xD;
&#xD;
          -  BRAHMS CgA II KRYPTOR baseline measurement available&#xD;
&#xD;
          -  Patient has discontinued the following treatments for at least 3 weeks before study&#xD;
             start: i) proton pump Inhibitors (PPI), ii) corticoids, iii) H2-receptor antagonists&#xD;
&#xD;
          -  Baseline Eastern Cooperative Oncology Group Performance Scale (ECOG PS) &lt;2&#xD;
&#xD;
          -  Written informed consent signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other active malignancy with the exclusion of melanoma or other cancers that occurred&#xD;
             more than 5 years ago&#xD;
&#xD;
          -  Participation in another clinical trial involving an investigational therapeutic&#xD;
             (exception: diagnostic studies and studies evaluating known therapies)&#xD;
&#xD;
          -  No measurable disease by RECIST criteria (Version 1.1)&#xD;
&#xD;
          -  Severe renal dysfunction defined as creatinine of 1.5x upper limit of normal (ULN)&#xD;
&#xD;
          -  Severe liver dysfunction in the absence of liver metastasis defined by aspartate&#xD;
             aminotransferase (AST), serum total bilirubin and/or alanine transaminase (ALT) 1.5x&#xD;
             ULN; severe liver dysfunction in the presence of liver metastasis defined by AST and&#xD;
             ALT over 5x ULN and total bilirubin over 1.5x ULN&#xD;
&#xD;
          -  Severe gastrointestinal disorders (chronic atrophic gastritis, pancreatitis,&#xD;
             inflammatory bowel disease, irritable bowel syndrome)&#xD;
&#xD;
          -  Severe cardiovascular disease (severe symptomatic congestive heart failure, pulmonary&#xD;
             artery hypertension, acute coronary syndrome)&#xD;
&#xD;
          -  Patients receiving active treatment with the following medications and samples were&#xD;
             collected less than 3 weeks after discontinuing: i) proton pump Inhibitors (PPI), ii)&#xD;
             corticoids, iii) H2-receptor antagonists&#xD;
&#xD;
          -  Chronic alcohol and/or substance abuse&#xD;
&#xD;
          -  Known pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel M Halperin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Texas MD Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité - Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.nccn.org/professionals/physician_gls/default.aspx</url>
    <description>National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines</description>
  </link>
  <results_reference>
    <citation>Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.</citation>
    <PMID>19097774</PMID>
  </results_reference>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>December 19, 2022</last_update_submitted>
  <last_update_submitted_qc>December 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Endocrine tumors</keyword>
  <keyword>Carcinoids</keyword>
  <keyword>Functional NETs</keyword>
  <keyword>Non-functional NETs</keyword>
  <keyword>Immunoassay</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
    <mesh_term>Stomach Neoplasms</mesh_term>
    <mesh_term>Intestinal Neoplasms</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/NCT03817866
org study id: Brahms-CASPAR
nct id: NCT03817866
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Gastroentero-pancreatic neuroendocrine tumors (GEP-NETs) are a heterogenous group of
      neoplasms that arise from enterochromaffin cells of the gastrointestinal (GI) tract and
      pancreas. They account for 50-70% of all incident NETs. Due to the lack of symptoms in the
      early stage of disease and the frequency of nonspecific GI symptoms, GEP-NETs are difficult
      to diagnose.

      Identification of effective biomarkers (such as Chromogranin A) to improve GEP-NET diagnosis,
      as well as to assess treatment efficacy, relapse and prognosis, is important for improving
      outcomes for patients with GEP-NETs.

      The purpose of this study is to validate the performance of Brahms (BRAHMS) Chromogranin A II
      Kryptor (KRYPTOR) assay to monitor the course of disease in patients with well-defined
      GEP-NETs.
A general characteristic for neuroendocrine tumors (NET) is expression of chromogranin A
      (CgA), which is released from neuroendocrine cells, occasionally together with cell specific
      hormones such as gastrin, insulin, somatostatin, and serotonin in functional tumors. Human
      CgA is an acidic 439 amino acid protein with a sequence containing several mono- and dibasic
      cleavage sites, and correspondingly, numerous fragments of CgA have been identified in tissue
      and plasma. CgA is critical to the formation of secretory granules that characterize NETs,
      and is therefore a useful marker for NETs.

      Plasma concentrations of CgA and/or CgA fragments are elevated in most NETs. Moreover, since
      plasma CgA concentrations seem to be closely related to tumor burden in humans, plasma CgA
      concentration is an important prognostic factor. As such, high plasma concentrations of CgA
      as well as a dramatic increase in plasma CgA within a short time period, is associated with a
      poorer prognosis. Plasma CgA has also been suggested to be useful in the follow-up of
      patients with NETs.

      Taken together, these observations support the notion that CgA is a promising biomarker
      candidate for monitoring treatment effectiveness and disease progression or regression.

      Participation in this clinical study requires no additional visits to the oncologist,
      radiology or the laboratory. All information needed for the study will be obtained during
      typical visits as recommended by the oncologist. Clinical assessment of patients with
      GEP-NETs (according to NCCN guidelines) is based on physical exam, imaging (CT or MRI scans)
      and laboratory parameters. The course of disease is followed by RECIST 1.1 categorization
      including the evaluation of tumor burden by imaging.
observational model: Cohort
time perspective: Prospective
measure: Disease Progression
time frame: 36 months
description: Progression vs. non-progression in patients with well-defined GEP-NETs assessed by RECIST 1.1 criteria
arm group label: BRAHMS CgA II KRYPTOR
description: Adult patients with well defined grade 1 and grade 2 GEP-NETs. Serial serum samples from all patients will be analyzed using the BRAHMS CgA II KRYPTOR Assay.
intervention type: Diagnostic Test
intervention name: BRAHMS CgA II KRYPTOR
description: The BRAHMS CgA II KRYPTOR kit is an automated immunofluorescent assay for the quantitative determination of the concentration of CgA in human serum.
The assay is to be used as an aid in monitoring disease progression during the course of disease and treatment in patients with GEP-NETs (grade 1 and grade 2).
Serial testing for patient BRAHMS CgA II KRYPTOR assay values should be used in conjunction with other clinical methods for monitoring GEP-NETs (grade 1 and grade 2).
arm group label: BRAHMS CgA II KRYPTOR
Serum samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Daniel M Halperin, MD
role: Principal Investigator
affiliation: The University of Texas MD Anderson Cancer Center
facility: 
facility: 
facility: 
facility: 
country: Germany
country: United States
url: https://www.nccn.org/professionals/physician_gls/default.aspx
description: National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines
citation: Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PMID: 19097774
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Colorectal Neoplasms
mesh term: Pancreatic Neoplasms
mesh term: Stomach Neoplasms
mesh term: Intestinal Neoplasms
sharing ipd: No