Clinical-pathological Evaluation of Pit-NETs (PitNET2024)

September 19, 2024 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Clinical-pathological Assessment of Pit-NETs: Data From a Large Multicenter Patients Cohort

Pituitary adenomas, namely pituitary neuroendocrine tumors (PitNETs), are recognized as rare neoplasia by national and international institutions.

Albeit most PitNETs are slow-growing with an indolent behavior, about one-third do not achieve biochemical control, recur, re-grow, and resist conventional treatments.

The predictors of aggressive behavior have not been identified for PitNETs. In 2013 Trouillas and coworkers developed a five tiered clinicopathological score by mixing histopathological data and clinico-radiological evidence of invasion. This system proved of prognostic value. Nonetheless, unlike for NET of gut and lung, no formal grading and/or staging tools were developed. In addition, PitNETs have not been thoroughly investigated by radiomics to predict clinical behavior, nor have druggable pathways been elucidated in PitNET cells to unveil new potential therapeutic approaches.

The first aim of this project is to define grading and staging tools for PitNETs based on: i) lineage-specific transcription factors ; ii) cell type specification by hormone production (prolactin, TSH, LH, FSH, ACTH, GH or none); iii) integration of standard radiological measures with recognized tools for clinical and pathological staging.

The second aim of this project is to investigate radiomics features as predictors of PitNETs behavior, prognosis, and treatment outcome.

The third aim of this project is to investigate whether the expression of molecular biomarkers [Vascular Endothelial Growth Factor (VEGF), Epithelial Growth Factor Receptor (EGFR), somatostatin receptors 1-5 (SSTRs), Fibroblast Growth Factor (FGF), mTOR (mammalian target of rapamycin), Programmed cells Death 1 (PD1) and its ligands (PD-L1), and Cytotoxic T Lymphocyte Associated protein 4 (CTLA4)] may impact on patients prognosis. Identifying new molecular pathways may help fine-tune and schedule the emerging targeted therapies for aggressive PitNETs, including mTOR inhibitors, VEGF, EGFR, and immune check-point inhibitors.

This study will investigate a large multicenter retrospective series of 740 PitNET patients and a prospective cohort of 200 patients to reach these objectives.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

940

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
    • Lazio
      • Roma, Lazio, Italy, 00168
        • Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC ANATOMIA PATOLOGICA
        • Contact:
        • Principal Investigator:
          • Guido Rindi
        • Sub-Investigator:
          • Francesco Doglietto
        • Sub-Investigator:
          • Sabrina Chiloiro

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

This study will investigate a large multicenter retrospective series of 740 PitNET patients and a prospective cohort of 200 patients

Description

Inclusion Criteria:

  • Consecutive patients older than 18 years;
  • availability of tumor samples for the required pathology analyses;
  • clinico-radiological follow-up of at least 5-10 years

Exclusion Criteria:

- Not applicable for this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Grating and staging
Time Frame: 2 years
To investigate the following pathological features of PitNET cell lineage-specific transcription factors, cell type specification by hormone production, proliferative index, p53, mitotic count, expression of somatostatin receptors, through immunohistochemistry analysis on formalin-fixed paraffin-embedded samples of PitNETs
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PitNET morphology analysis
Time Frame: 2 years
Identification of PitNET morphology features, as tumor maximum diameter, volume, sites of tumor extensions and invasion, and grading of cavernous sinus invasion though the revision of pre-surgical magnetic resonance images
2 years
Radiomics
Time Frame: 2 years
Radiomics features will be extracted and computed using the different standardized methods and platforms for quantitative imaging analysis though different standardized methods and platforms for quantitative imaging analysis. Radiomics analysis will be realized after segmentations test-retest, to evaluate and quantify features' reproducibility.
2 years
Molecular test: proteomics
Time Frame: 2 years
To investigate on PitNets the expression of Vascular Endothelial Growth Factor (VEGF), Epithelial Growth Factor Receptor (EGFR), somatostatin receptors 1-5 (SSTRs), Fibroblast Growth Factor (FGF), mTOR (mammalian target of rapamycin), Programmed cells Death 1 (PD1) and its ligands (PD-L1), and Cytotoxic T Lymphocyte Associated protein 4 (CTLA4)] through proteomic analysis on formalin-fixed paraffin-embedded samples of PitNETs for patients retrospectively included and on frozen tissues for patients prospectively enrolled.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

  • Principal Investigator: Guido Rindi, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2024

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

September 17, 2024

First Submitted That Met QC Criteria

September 19, 2024

First Posted (Actual)

September 23, 2024

Study Record Updates

Last Update Posted (Actual)

September 23, 2024

Last Update Submitted That Met QC Criteria

September 19, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6859

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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