<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/NCT04464122</url>
  </required_header>
  <id_info>
    <org_study_id>Reborn Study</org_study_id>
    <nct_id>NCT04464122</nct_id>
  </id_info>
  <brief_title>Rediscovering Biomarkers for the Diagnosis and Early Treatment Response in NEN (REBORN)</brief_title>
  <acronym>REBORN</acronym>
  <official_title>Rediscovering Biomarkers for the Diagnosis and Early Treatment Response in NEN. REBORN Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Roma La Sapienza</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Roma La Sapienza</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>
      This is a multicentre, controlled, observational prospective study on new biomarkers, as&#xD;
      immune profiling, angiogenetic markers and circRNA from TEPs in the diagnosis and in the&#xD;
      evaluation of treatment response in pulmonary and gastro-entero-pancreatic NENs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Neuroendocrine Neoplasm (NEN) are heterogeneous disease in terms of origin, localization and&#xD;
      clinical presentation. Annual incidence of NEN is increasing in the last 30 years, even if&#xD;
      the reasons underlying this rise have not been completely identified.&#xD;
&#xD;
      Many biomarkers have been used in the diagnosis and follow-up of patients with NEN. In&#xD;
      non-functioning NEN general tumor markers, such as chromogranin A (CgA) and neuron specific&#xD;
      enolase (NSE), are commonly used but their sensibility and specificity are quite low.&#xD;
&#xD;
      Recently, high-throughput tissue microarray and immunohistochemistry assessments have been&#xD;
      performed to observe the expression pattern of new potential markers for NEN. In order to&#xD;
      overcome limitations of tissue acquisition, the use of liquid biopsies has been advocated. It&#xD;
      has been reported that tumor-educated platelets (TEPs) may easily enable blood-based cancer&#xD;
      diagnostics. TEPs take up tumor-derived secreted membrane vesicles containing RNAs, of which&#xD;
      circular RNAs (circRNAs) that can serve as a potential biomarker source for cancer&#xD;
      diagnostics. This innovative approach in cancer detection has not yet been transferred to the&#xD;
      NEN field.&#xD;
&#xD;
      Flow cytometric analysis furnishes important insights into the immune status by providing&#xD;
      information about the numbers and phenotypes of the immune cells, which are known to be&#xD;
      altered in many types of neoplasms. In NEN, leukocytes subpopulations and peripheral blood&#xD;
      mononuclear cells (PBMCs) are not been completely investigated but immunological alterations&#xD;
      could represent a signal of neoplastic spread.&#xD;
&#xD;
      Inflammatory and angiogenetic pathways' involvement in NEN behavior has recently received&#xD;
      increasing attention. It is well known that NEN are known to be highly vascularized neoplasms&#xD;
      and somatostatin analogues (SSA), used as first line drugs for most well differentiated NEN,&#xD;
      can reduce tumour proliferation by various direct and indirect mechanism including the&#xD;
      inhibition of angiogenesis.&#xD;
&#xD;
      Tumor angiogenesis is a complicated process consisting of several steps, the angiogenesis&#xD;
      cascade, regulated by endogenous and exogenous factors, including the system Angiopoietin-1&#xD;
      (Ang-1) and -2 (Ang-2) / Tie2 and Prokineticins. These systems are involved in neoplastic&#xD;
      angiogenesis and inflammation in various types of cancer. Despite these evidences, the role&#xD;
      of inflammatory and angiogenic factors in NEN detection and follow-up has not been completely&#xD;
      clarified.&#xD;
&#xD;
      The aim of the study is to evaluate immune profiling, angiogenetic markers and circularRNA&#xD;
      sequencing in patients affected by locally advanced or metastatic pulmonary or GEP NENs and&#xD;
      controls. Moreover, NENs patients will be evaluated also after 1 and 3 months of first line&#xD;
      medical treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 14, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 14, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate the modification of the angiogenetic mediator sTie2 after treatment.</measure>
    <time_frame>baseline - + 1 month - +3 months</time_frame>
    <description>Modification of sTie (soluble Tie2) after treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To evaluate the difference in the angiogenetic mediator sTie2 between patients and controls</measure>
    <time_frame>baseline</time_frame>
    <description>Comparison of basal levels of sTie between patients and controls</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To validate the use of circular RNAs from TEPs in NEN diagnosis</measure>
    <time_frame>baseline</time_frame>
    <description>Validation of the use of circular RNAs sequencing from tumor educated platelets (TEPs) in NETs diagnosis, through the comparison between patients and controls</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the changing in circular RNAs from TEPs in NEN patients after somatostatin analogs treatment</measure>
    <time_frame>baseline - + 1 month - +3 months</time_frame>
    <description>Modification in circular RNAs sequencing from tumor educated platelets (TEPs) in patients after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare circular and cellular angiogenesis mediators between patients and controls</measure>
    <time_frame>baseline</time_frame>
    <description>Comparison of basal level of other circular and cellular angiogenesis mediators between patients and controls (Angiogenic factors: ANG1, ANG2, FGF1, FGF2, NRP1, NRP2, VEGFA, VEGFB, VEGFC, HIF1A, NOS3, PROK1, PROK2; Cytokines: CCL11, CCL2, CXCL1, CXCL10, CXCL5, CXCL6, CXCL9, IL1B, IL6, TNF; Receptors and other angiogenic factors: VEGFR1, VEGFR2, TIE2, PDGFR, TGFBR, MMP14, MMP2, MMp9, TIMP1, TIMP2, TIMP3, PROKR1, PROKR2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the changing in circular and cellular angiogenesis mediators after treatment.</measure>
    <time_frame>baseline - + 1 month - +3 months</time_frame>
    <description>Modification of other circular and cellular angiogenesis mediators in patients after treatment (Angiogenic factors: ANG1, ANG2, FGF1, FGF2, NRP1, NRP2, VEGFA, VEGFB, VEGFC, HIF1A, NOS3, PROK1, PROK2; Cytokines: CCL11, CCL2, CXCL1, CXCL10, CXCL5, CXCL6, CXCL9, IL1B, IL6, TNF; Receptors and other angiogenic factors: VEGFR1, VEGFR2, TIE2, PDGFR, TGFBR, MMP14, MMP2, MMp9, TIMP1, TIMP2, TIMP3, PROKR1, PROKR2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To quantify PBMC subpopulation in patients and controls</measure>
    <time_frame>baseline</time_frame>
    <description>Quatification of peripheral blood mononuclear cells (PBMC) subpopulations in patients and controls</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the modification of PBMC subpopulation in patients after treatment</measure>
    <time_frame>baseline - + 1 month - +3 months</time_frame>
    <description>Modification of peripheral blood mononuclear cells (PBMC) subpopulations in patients after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare classical neuroendocrine markers serum levels between patients and controls</measure>
    <time_frame>baseline</time_frame>
    <description>Comparison of basal serum level of classical neuroendocrine markers (chromogranin a and neuron specific enolase) between patients and controls</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the modification of classical neuroendocrine markers in patients after treatment</measure>
    <time_frame>baseline - + 1 month - +3 months</time_frame>
    <description>Modification of classical neuroendocrine markers (chromogranin a and neuron specific enolase) in patients after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate infectious diseases frequency and severity between patients and controls</measure>
    <time_frame>baseline</time_frame>
    <description>Frequencies and severity of infectious diseases will be evaluated by modified Infectious Diseases Questionnaire (GNC). This questionnaire includes questions on infectious diseases of upper and lower respiratory tract, gastrointestinal tract, skin and urogenital tract contracted during the previous 12 months. Questions investigate on the number and duration of infections, necessity of antibiotic or antifungal therapy, hospital stay and days of absence from work. Final score represents the frequency of infections. Moreover, some questions investigate possible susceptible or protective factors for infectious diseases: vaccinations, use of corticosteroids, concomitant diseases, previous appendectomy, tonsillectomy, adenoidectomy, splenectomy or thymectomy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the difference in quality of life questionnaire in patients and controls</measure>
    <time_frame>baseline</time_frame>
    <description>Quality of life will be evaluated by the Physical Component score and the Mental Component score of the self-administered questionnaire SF-36-Item Health Survey questionnaire. This questionnaire measures eight scales: physical functioning, role physical, bodily pain, general health (physical component) and vitality, social functioning, role emotional, mental health (mental component).&#xD;
Interpretation of the score will be the following: at each item of the questionnaire corresponds a percentage value (from 0% to 100%). The average of the single items constitutes the scale total percentage (from 0% to 100%); missing data are not considered during calculation. High score defines a more favorable health state.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the modification in quality of life questionnaire in patients after treatment</measure>
    <time_frame>baseline - + 1 month - +3 months</time_frame>
    <description>Quality of life will be evaluated by the Physical Component score and the Mental Component score of the self-administered questionnaire SF-36-Item Health Survey questionnaire. This questionnaire measures eight scales: physical functioning, role physical, bodily pain, general health (physical component) and vitality, social functioning, role emotional, mental health (mental component).&#xD;
Interpretation of the score will be the following: at each item of the questionnaire corresponds a percentage value (from 0% to 100%). The average of the single items constitutes the scale total percentage (from 0% to 100%); missing data are not considered during calculation. High score defines a more favorable health state.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Neuroendocrine Tumors</condition>
  <condition>Neuroendocrine Neoplasm</condition>
  <condition>Neuroendocrine Tumor Grade 1</condition>
  <condition>Neuroendocrine Tumor Grade 2</condition>
  <condition>Neuroendocrine Carcinoma</condition>
  <arm_group>
    <arm_group_label>Neuroendocrine toumor group</arm_group_label>
    <description>30 patients (18-80 years, males and females) affected by histologically-proven neuroendocrine neoplasms, locally advanced or metastatic, originating from pulmonary or gastro-entero-pancreatic (GEP) tract, candidate to medical therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <description>Patients affected by other non-malignant endocrine disease, e.g. benign thyroid disfunction (18-80 years, males and females)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Somatostatin analog; chemotherapy</intervention_name>
    <description>According to current ENETS guidelines, patients will be treated by somatostatin analogs or chemotherapy, recommended respectively as first line therapy in neuroendocrine tumours or neuroendocrine neoplasms.</description>
    <arm_group_label>Neuroendocrine toumor group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with histologically-proven NENs, locally advanced or metastatic, originating from&#xD;
        pulmonary or gastro-entero-pancreatic tract&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically-proven NENs, locally advanced or metastatic, originating from pulmonary&#xD;
             or gastro-entero-pancreatic (GEP) tract, candidate to first line medical therapy&#xD;
             (study group);&#xD;
&#xD;
          -  Patients affected by other non-malignant endocrine disease, e.g. benign thyroid&#xD;
             disfunction (control group).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe chronic kidney disease (stage 4-5);&#xD;
&#xD;
          -  Clinical or laboratory signs of significant respiratory, cardiological and&#xD;
             hepatobiliary disease;&#xD;
&#xD;
          -  Other non-neuroendocrine malignancies.&#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>Andrea M Isidori, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Experimental Medicine, Sapienza University of Rome</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Andrea M Isidori, MD, PhD</last_name>
    <phone>+390649970540</phone>
    <email>andrea.isidori@uniroma1.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Elisa M Giannetta, MD, PhD</last_name>
    <phone>+390649970540</phone>
    <email>elisa.giannetta@uniroma1.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Andrea M Isidori</name>
      <address>
        <city>Rome</city>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrea M Isidori, MD, PhD</last_name>
      <phone>00390649970540</phone>
      <email>andrea.isidori@uniroma1.it</email>
    </contact>
    <investigator>
      <last_name>Andrea M Isidori, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Elisa Giannetta, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Antongiulio Faggiano, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mary Anna Venneri, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Maria Grazia Tarsitano, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Giulia Puliani, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tiziana Feola, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Franz Sesti, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Francesca Sciarra, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Sol N, Wurdinger T. Platelet RNA signatures for the detection of cancer. Cancer Metastasis Rev. 2017 Jun;36(2):263-272. doi: 10.1007/s10555-017-9674-0.</citation>
    <PMID>28681241</PMID>
  </reference>
  <reference>
    <citation>Joosse SA, Pantel K. Tumor-Educated Platelets as Liquid Biopsy in Cancer Patients. Cancer Cell. 2015 Nov 9;28(5):552-554. doi: 10.1016/j.ccell.2015.10.007.</citation>
    <PMID>26555171</PMID>
  </reference>
  <reference>
    <citation>Fiedler U, Augustin HG. Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol. 2006 Dec;27(12):552-8. doi: 10.1016/j.it.2006.10.004. Epub 2006 Oct 12.</citation>
    <PMID>17045842</PMID>
  </reference>
  <reference>
    <citation>Monnier J, Samson M. Prokineticins in angiogenesis and cancer. Cancer Lett. 2010 Oct 28;296(2):144-9. doi: 10.1016/j.canlet.2010.06.011. Epub 2010 Jul 14.</citation>
    <PMID>20633984</PMID>
  </reference>
  <reference>
    <citation>Best MG, Sol N, Kooi I, Tannous J, Westerman BA, Rustenburg F, Schellen P, Verschueren H, Post E, Koster J, Ylstra B, Ameziane N, Dorsman J, Smit EF, Verheul HM, Noske DP, Reijneveld JC, Nilsson RJA, Tannous BA, Wesseling P, Wurdinger T. RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics. Cancer Cell. 2015 Nov 9;28(5):666-676. doi: 10.1016/j.ccell.2015.09.018. Epub 2015 Oct 29.</citation>
    <PMID>26525104</PMID>
  </reference>
  <reference>
    <citation>Harris AL, Reusch P, Barleon B, Hang C, Dobbs N, Marme D. Soluble Tie2 and Flt1 extracellular domains in serum of patients with renal cancer and response to antiangiogenic therapy. Clin Cancer Res. 2001 Jul;7(7):1992-7.</citation>
    <PMID>11448916</PMID>
  </reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>November 22, 2022</last_update_submitted>
  <last_update_submitted_qc>November 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Roma La Sapienza</investigator_affiliation>
    <investigator_full_name>Andrea M. Isidori</investigator_full_name>
    <investigator_title>Full Professor</investigator_title>
  </responsible_party>
  <keyword>Neuroendocrine Tumours</keyword>
  <keyword>Prognostic markers</keyword>
  <keyword>Tumour educated platelets</keyword>
  <keyword>angiogenesis</keyword>
  <keyword>immune function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Neuroendocrine Tumors</mesh_term>
    <mesh_term>Carcinoma, Neuroendocrine</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Somatostatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04464122
org study id: Reborn Study
nct id: NCT04464122
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a multicentre, controlled, observational prospective study on new biomarkers, as
      immune profiling, angiogenetic markers and circRNA from TEPs in the diagnosis and in the
      evaluation of treatment response in pulmonary and gastro-entero-pancreatic NENs.
Neuroendocrine Neoplasm (NEN) are heterogeneous disease in terms of origin, localization and
      clinical presentation. Annual incidence of NEN is increasing in the last 30 years, even if
      the reasons underlying this rise have not been completely identified.

      Many biomarkers have been used in the diagnosis and follow-up of patients with NEN. In
      non-functioning NEN general tumor markers, such as chromogranin A (CgA) and neuron specific
      enolase (NSE), are commonly used but their sensibility and specificity are quite low.

      Recently, high-throughput tissue microarray and immunohistochemistry assessments have been
      performed to observe the expression pattern of new potential markers for NEN. In order to
      overcome limitations of tissue acquisition, the use of liquid biopsies has been advocated. It
      has been reported that tumor-educated platelets (TEPs) may easily enable blood-based cancer
      diagnostics. TEPs take up tumor-derived secreted membrane vesicles containing RNAs, of which
      circular RNAs (circRNAs) that can serve as a potential biomarker source for cancer
      diagnostics. This innovative approach in cancer detection has not yet been transferred to the
      NEN field.

      Flow cytometric analysis furnishes important insights into the immune status by providing
      information about the numbers and phenotypes of the immune cells, which are known to be
      altered in many types of neoplasms. In NEN, leukocytes subpopulations and peripheral blood
      mononuclear cells (PBMCs) are not been completely investigated but immunological alterations
      could represent a signal of neoplastic spread.

      Inflammatory and angiogenetic pathways' involvement in NEN behavior has recently received
      increasing attention. It is well known that NEN are known to be highly vascularized neoplasms
      and somatostatin analogues (SSA), used as first line drugs for most well differentiated NEN,
      can reduce tumour proliferation by various direct and indirect mechanism including the
      inhibition of angiogenesis.

      Tumor angiogenesis is a complicated process consisting of several steps, the angiogenesis
      cascade, regulated by endogenous and exogenous factors, including the system Angiopoietin-1
      (Ang-1) and -2 (Ang-2) / Tie2 and Prokineticins. These systems are involved in neoplastic
      angiogenesis and inflammation in various types of cancer. Despite these evidences, the role
      of inflammatory and angiogenic factors in NEN detection and follow-up has not been completely
      clarified.

      The aim of the study is to evaluate immune profiling, angiogenetic markers and circularRNA
      sequencing in patients affected by locally advanced or metastatic pulmonary or GEP NENs and
      controls. Moreover, NENs patients will be evaluated also after 1 and 3 months of first line
      medical treatment.
observational model: Case-Control
time perspective: Prospective
measure: To evaluate the modification of the angiogenetic mediator sTie2 after treatment.
time frame: baseline - + 1 month - +3 months
description: Modification of sTie (soluble Tie2) after treatment
measure: To evaluate the difference in the angiogenetic mediator sTie2 between patients and controls
time frame: baseline
description: Comparison of basal levels of sTie between patients and controls
measure: To validate the use of circular RNAs from TEPs in NEN diagnosis
time frame: baseline
description: Validation of the use of circular RNAs sequencing from tumor educated platelets (TEPs) in NETs diagnosis, through the comparison between patients and controls
measure: To evaluate the changing in circular RNAs from TEPs in NEN patients after somatostatin analogs treatment
time frame: baseline - + 1 month - +3 months
description: Modification in circular RNAs sequencing from tumor educated platelets (TEPs) in patients after treatment
measure: To compare circular and cellular angiogenesis mediators between patients and controls
time frame: baseline
description: Comparison of basal level of other circular and cellular angiogenesis mediators between patients and controls (Angiogenic factors: ANG1, ANG2, FGF1, FGF2, NRP1, NRP2, VEGFA, VEGFB, VEGFC, HIF1A, NOS3, PROK1, PROK2; Cytokines: CCL11, CCL2, CXCL1, CXCL10, CXCL5, CXCL6, CXCL9, IL1B, IL6, TNF; Receptors and other angiogenic factors: VEGFR1, VEGFR2, TIE2, PDGFR, TGFBR, MMP14, MMP2, MMp9, TIMP1, TIMP2, TIMP3, PROKR1, PROKR2)
measure: To evaluate the changing in circular and cellular angiogenesis mediators after treatment.
time frame: baseline - + 1 month - +3 months
description: Modification of other circular and cellular angiogenesis mediators in patients after treatment (Angiogenic factors: ANG1, ANG2, FGF1, FGF2, NRP1, NRP2, VEGFA, VEGFB, VEGFC, HIF1A, NOS3, PROK1, PROK2; Cytokines: CCL11, CCL2, CXCL1, CXCL10, CXCL5, CXCL6, CXCL9, IL1B, IL6, TNF; Receptors and other angiogenic factors: VEGFR1, VEGFR2, TIE2, PDGFR, TGFBR, MMP14, MMP2, MMp9, TIMP1, TIMP2, TIMP3, PROKR1, PROKR2)
measure: To quantify PBMC subpopulation in patients and controls
time frame: baseline
description: Quatification of peripheral blood mononuclear cells (PBMC) subpopulations in patients and controls
measure: To evaluate the modification of PBMC subpopulation in patients after treatment
time frame: baseline - + 1 month - +3 months
description: Modification of peripheral blood mononuclear cells (PBMC) subpopulations in patients after treatment
measure: To compare classical neuroendocrine markers serum levels between patients and controls
time frame: baseline
description: Comparison of basal serum level of classical neuroendocrine markers (chromogranin a and neuron specific enolase) between patients and controls
measure: To evaluate the modification of classical neuroendocrine markers in patients after treatment
time frame: baseline - + 1 month - +3 months
description: Modification of classical neuroendocrine markers (chromogranin a and neuron specific enolase) in patients after treatment
measure: To evaluate infectious diseases frequency and severity between patients and controls
time frame: baseline
description: Frequencies and severity of infectious diseases will be evaluated by modified Infectious Diseases Questionnaire (GNC). This questionnaire includes questions on infectious diseases of upper and lower respiratory tract, gastrointestinal tract, skin and urogenital tract contracted during the previous 12 months. Questions investigate on the number and duration of infections, necessity of antibiotic or antifungal therapy, hospital stay and days of absence from work. Final score represents the frequency of infections. Moreover, some questions investigate possible susceptible or protective factors for infectious diseases: vaccinations, use of corticosteroids, concomitant diseases, previous appendectomy, tonsillectomy, adenoidectomy, splenectomy or thymectomy.
measure: To evaluate the difference in quality of life questionnaire in patients and controls
time frame: baseline
description: Quality of life will be evaluated by the Physical Component score and the Mental Component score of the self-administered questionnaire SF-36-Item Health Survey questionnaire. This questionnaire measures eight scales: physical functioning, role physical, bodily pain, general health (physical component) and vitality, social functioning, role emotional, mental health (mental component).
Interpretation of the score will be the following: at each item of the questionnaire corresponds a percentage value (from 0% to 100%). The average of the single items constitutes the scale total percentage (from 0% to 100%); missing data are not considered during calculation. High score defines a more favorable health state.
measure: To evaluate the modification in quality of life questionnaire in patients after treatment
time frame: baseline - + 1 month - +3 months
description: Quality of life will be evaluated by the Physical Component score and the Mental Component score of the self-administered questionnaire SF-36-Item Health Survey questionnaire. This questionnaire measures eight scales: physical functioning, role physical, bodily pain, general health (physical component) and vitality, social functioning, role emotional, mental health (mental component).
Interpretation of the score will be the following: at each item of the questionnaire corresponds a percentage value (from 0% to 100%). The average of the single items constitutes the scale total percentage (from 0% to 100%); missing data are not considered during calculation. High score defines a more favorable health state.
arm group label: Neuroendocrine toumor group
description: 30 patients (18-80 years, males and females) affected by histologically-proven neuroendocrine neoplasms, locally advanced or metastatic, originating from pulmonary or gastro-entero-pancreatic (GEP) tract, candidate to medical therapy.
arm group label: Control group
description: Patients affected by other non-malignant endocrine disease, e.g. benign thyroid disfunction (18-80 years, males and females)
intervention type: Drug
intervention name: Somatostatin analog; chemotherapy
description: According to current ENETS guidelines, patients will be treated by somatostatin analogs or chemotherapy, recommended respectively as first line therapy in neuroendocrine tumours or neuroendocrine neoplasms.
arm group label: Neuroendocrine toumor group
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Andrea M Isidori, MD, PhD
role: Principal Investigator
affiliation: Department of Experimental Medicine, Sapienza University of Rome
last name: Andrea M Isidori, MD, PhD
phone: +390649970540
email: andrea.isidori@uniroma1.it
last name: Elisa M Giannetta, MD, PhD
phone: +390649970540
email: elisa.giannetta@uniroma1.it
facility: 
status: Recruiting
contact: 
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country: Italy
citation: Sol N, Wurdinger T. Platelet RNA signatures for the detection of cancer. Cancer Metastasis Rev. 2017 Jun;36(2):263-272. doi: 10.1007/s10555-017-9674-0.
PMID: 28681241
citation: Joosse SA, Pantel K. Tumor-Educated Platelets as Liquid Biopsy in Cancer Patients. Cancer Cell. 2015 Nov 9;28(5):552-554. doi: 10.1016/j.ccell.2015.10.007.
PMID: 26555171
citation: Fiedler U, Augustin HG. Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol. 2006 Dec;27(12):552-8. doi: 10.1016/j.it.2006.10.004. Epub 2006 Oct 12.
PMID: 17045842
citation: Monnier J, Samson M. Prokineticins in angiogenesis and cancer. Cancer Lett. 2010 Oct 28;296(2):144-9. doi: 10.1016/j.canlet.2010.06.011. Epub 2010 Jul 14.
PMID: 20633984
citation: Best MG, Sol N, Kooi I, Tannous J, Westerman BA, Rustenburg F, Schellen P, Verschueren H, Post E, Koster J, Ylstra B, Ameziane N, Dorsman J, Smit EF, Verheul HM, Noske DP, Reijneveld JC, Nilsson RJA, Tannous BA, Wesseling P, Wurdinger T. RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics. Cancer Cell. 2015 Nov 9;28(5):666-676. doi: 10.1016/j.ccell.2015.09.018. Epub 2015 Oct 29.
PMID: 26525104
citation: Harris AL, Reusch P, Barleon B, Hang C, Dobbs N, Marme D. Soluble Tie2 and Flt1 extracellular domains in serum of patients with renal cancer and response to antiangiogenic therapy. Clin Cancer Res. 2001 Jul;7(7):1992-7.
PMID: 11448916
responsible party type: Principal Investigator
investigator affiliation: University of Roma La Sapienza
investigator full name: Andrea M. Isidori
investigator title: Full Professor
mesh term: Neoplasms
mesh term: Neuroendocrine Tumors
mesh term: Carcinoma, Neuroendocrine
mesh term: Somatostatin
sharing ipd: Undecided