NCT Number: NCT04464122
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.
Interested in participating?
Request Info18 year–80 year
All sexes
Observational
Rome, Italy, 00161
Location status: Recruiting
Andrea M Isidori, MD, PhD
CONTACT
Andrea M Isidori, MD, PhD
PRINCIPAL_INVESTIGATOR
Antongiulio Faggiano, MD, PhD
SUB_INVESTIGATOR
Elisa Giannetta, MD, PhD
SUB_INVESTIGATOR
Francesca Sciarra, PhD
SUB_INVESTIGATOR
Franz Sesti, MD
SUB_INVESTIGATOR
Giulia Puliani, MD
SUB_INVESTIGATOR
Maria Grazia Tarsitano, MD, PhD
SUB_INVESTIGATOR
Mary Anna Venneri, PhD
SUB_INVESTIGATOR
Tiziana Feola, MD
SUB_INVESTIGATOR
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.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
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.
Time frame: baseline - + 1 month - +3 months
Modification of sTie (soluble Tie2) after treatment
Time frame: baseline
Comparison of basal levels of sTie between patients and controls
Time frame: baseline
Validation of the use of circular RNAs sequencing from tumor educated platelets (TEPs) in NETs diagnosis, through the comparison between patients and controls
Time frame: baseline - + 1 month - +3 months
Modification in circular RNAs sequencing from tumor educated platelets (TEPs) in patients after treatment
Time frame: baseline
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)
Time frame: baseline - + 1 month - +3 months
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)
Time frame: baseline
Quatification of peripheral blood mononuclear cells (PBMC) subpopulations in patients and controls
Time frame: baseline - + 1 month - +3 months
Modification of peripheral blood mononuclear cells (PBMC) subpopulations in patients after treatment
Time frame: baseline
Comparison of basal serum level of classical neuroendocrine markers (chromogranin a and neuron specific enolase) between patients and controls
Time frame: baseline - + 1 month - +3 months
Modification of classical neuroendocrine markers (chromogranin a and neuron specific enolase) in patients after treatment
Time frame: baseline
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.
Time frame: baseline
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.
Time frame: baseline - + 1 month - +3 months
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.
Contact information is provided by the study sponsor or research team.
Andrea M Isidori, MD, PhD
CONTACT
Elisa M Giannetta, MD, PhD
CONTACT
University of Roma La Sapienza
Other
Rediscovering Biomarkers for the Diagnosis and Early Treatment Response in NEN. REBORN Study
Acronym: REBORN
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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