68-Ga-labeled Octreotide Analogues PET in Duodenal-pancreatic Neuroendocrine Tumours

NCT01673906 | Completed Phase 2 DMC

• 1 other identifier: 2012-000994-22
• Study Type: interventional
• Target: 142
• Locations: 2 countries
• Sites: 21

Brief Summary

The diagnostic work-up of patients suspected of having neuroendocrine tumours (NETs) has traditionally been a challenging issue. The last two decades have been marked by the application to use in the diagnosis of NETs of 3 newly available diagnostic techniques: endoscopic ultrasonography (EUS), multidetector CT (MDCT), and more recently, positron emission tomography using 68Ga-labelled octreotide analogues (PET). In a prospective study conducted at a single referral centre that compared PET with conventional somatostatin receptor scintigraphy and MDCT in diagnosis, staging and follow-up of patients affected by NET, PET detected more primary and secondary lesions than other methods. Recent studies investigated the clinical impact of PET in the management of patients affected by NET, previously studied by MDCT. The investigators recently reported the results of the investigation of 19 patients suspected of having primary pancreatic NET and studied by PET, MDCT and EUS. The investigators preliminary data suggest that PET may be slightly more sensitive than MDCT in detecting small (\<2cm) pancreatic lesions; accuracy of PET and EUS is probably similar. No prospective study has yet been devoted to evaluate the accuracy of PET in the diagnosis and staging of primary duodenal-pancreatic NETs. Furthermore, the clinical impact of the adjunct of PET to the traditional protocols of diagnosis and staging of these tumours waits to be thoroughly evaluated. Thus the appropriate place of PET in the diagnostic algorithm of patients suspected of having duodenal-pancreatic NET remains undefined. The main aim of this project is to prospectively compare the accuracy of PET and MDCT in the diagnosis and staging of patients suspected of having duodenal-pancreatic NETs. The investigators hypothesised that PET is superior to MDCT in the diagnosis of these neoplasm (the dimension of the study sample is estimated in order to detect a 10% difference). The impact of PET on management plan of affected patients will also be evaluated. As a secondary endpoint of the study, the investigators will compare EUS, PET and MDCT in the diagnosis of primary duodenal-pancreatic NET. The study is designed as a multicentre, prospective, non-randomised clinical trial. All patients will undergo MDCT, PET and EUS in this fixed order.

Conditions

Neuroendocrine Tumours

Keywords

positron-emission tomography; neuroendocrine tumors; endosonography; tomography, X-ray computed; biopsy, fine needle; sensitivity and sensibility

Outcome Measures

Primary Outcomes (2)

• Accuracy of the diagnostic test.

  Accuracy was computed as: (number of true positives + true negatives)/(number + true positives + true negatives + false positives + false negatives). Accuracy of MDCT and PET in the diagnosis of primary duodenal-pancreatic NET will be calculated on a patient basis and they will be compared using McNemar test. Reference standard will be considered the diagnoses of primary NET, when supported by unambiguous cytology, histology or by at least one year of follow up.In cases of disagreement between cytological and histological findings, histology will be the gold standard.

  one year

• Accuracy of the diagnostic test (after exclusion of patients enrolled due to a incidentally diagnosed lesion)

  Accuracy was calculated as above, but based on subjects matching criteria 1-7 of the list of clinical situations suggestive for NET (see below, inclusion criteria). Patients with a lesion suspicion of NET incidentally diagnosed during abdominal ultrasound or MDCT not performed for clinical suspicion of NET were excluded.

  one year

Secondary Outcomes (5)

• Number of Participants with Adverse Events as a Measure of Safety.

  one year

• Sensitivity of the diagnostic tests.

  one year

• Specificity of the diagnostic tests.

  one year

• Clinical impact of PET.

  one year

• Diameter of lesions.

  one year

Other Outcomes (1)

• Accuracy of EUS-FNA

  one year

Study Arms (1)

Diagnostic work up

EXPERIMENTAL

The patients enrolled in the study (see below), with a consistent clinical suspicion of a primary duodenal-pancreatic NET.

Drug: Diagnostic work up

Interventions

Diagnostic work up DRUG

Patients will undergo MDCT, PET and EUS. Every attempt will be made to achieve a pre-operative cytologic diagnosis of any primary lesion by EUS-FNA. All diagnostic tests (MDCT, PET, EUS) should be performed during a two month time span, in this fixed order. The nuclear medicine doctor will be blinded of findings of MDCT. The gastroenterologist will be blinded about the findings of MDCT and PET until he has completed the diagnostic EUS. For ethical reasons, the findings of MDCT and PET will be disclosed to her/him, while the patient is still sedated in the operating room, just before the FNA. The minimal technical requirement for the techniques, the requested levels of clinical competence of the operators and the procedure for critical revision of radiological and cytological and histological specimens are detailed in the protocol. For PET any 68Ga -labeled-octreotide analogue will be allowed. Before EUS, an extended-esophagogastroduodenoscopy (until the Treitz) until will be performed.

Diagnostic work up

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients affected by proved MEN-I, in whom a neoplasm in the duodenal-pancreatic area is suspected.
• Patients with clinical diagnosis of carcinoid syndrome.
• Patients with clinical diagnosis of Zollinger-Ellison syndrome.
• Patients with insulinoma, as proved by fasting test.
• Patient with clinical pictures and laboratory findings suggesting other functional or non-functional NET.
• Patients who had previously undergone surgery, including total and subtotal pancreatectomy, or a duodenotomy, intended as curative for a histologically confirmed NET.
• Patients who were diagnosed with NET metastasis with unknown primary location of the disease.
• Patients undergoing diagnostic work-up for a periduodenal or pancreatic lesion incidentally found during abdominal ultrasound (not performed for suspicion of a NET) and with ultrasonographic characteristics (rounded, hypoechoic or egg-eye, well demarcated) suspicious for NET.
• Patients undergoing diagnostic work-up for a periduodenal or pancreatic lesion incidentally found during TC (not performed for suspicion of a NET) and with radiological characteristics (well demarcated, hypervascular) suspicious for NET.

You may not qualify if:

• Patient unwilling, or unable to consent.
• Pregnancy, or lactation.
• Age \<18 years
• Known diagnosis of duodenal-pancreatic NET.
• Patients with concomitant life-threatening disease.
• Patients who had already undergone PET or EUS, in the last six months. In particular patients should be excluded from the study, when a lesion in the duodenal-pancreatic area, with characteristic suspicious for a NET, is incidentally diagnosed by PET, or EUS, or when a previously unsuspected diagnosis of NET is suggested by EUS-FNA of a pancreatic lesion.
• Patients who had previously undergone total gastrectomy or pancreatectomy will be included in the study, but they will not undergo EUS.

Sponsors & Collaborators

• Azienda USL Reggio Emilia - IRCCS: lead

Study Sites (21)

Irene Virgolini

Innsbruck, Innsbruck, Austria

Location

Nadia Cremonini

Bologna, Bologna, Italy

Location

Fernando Cirillo

Cremona, Cremona, Italy

Location

Diego Ferone

Genova, Genova, Italy

Location

Giovanna Pepe

Milan, Milano, Italy

Location

Rita Conigliaro

Modena, Modena, 41121, Italy

Location

Luppi Gabriele

Modena, Modena, Italy

Location

Pellegrino Crafa

Parma, Parma, 43121, Italy

Location

Piero Ferolla

Perugia, Perugia, Italy

Location

Antonio Chella

Pisa, Pisa, Italy

Location

Laura Scaltriti

Guastalla, Reggio Emilia, 42100, Italy

Location

ASMN IRCCS Reggio Emilia

Reggio Emilia, RE, 42100, Italy

Location

Enrico Papini

Albano Laziale, Roma, Italy

Location

Roberto Baldelli

Roma, Roma, Italy

Location

Vittoria Rufini

Roma, Roma, Italy

Location

Claudio De Angelis

Torino, Torino, Italy

Location

Marco Gallo

Torino, Torino, Italy

Location

Paolo Limone

Torino, Torino, Italy

Location

Franco Grimaldi

Udine, Udine, Italy

Location

Massimo Falconi

Verona, Verona, Italy

Location

Roberto Castello

Verona, Verona, Italy

Location

Related Publications (3)

• Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C, Kovacs P, Von Guggenberg E, Bale R, Virgolini IJ. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med. 2007 Apr;48(4):508-18. doi: 10.2967/jnumed.106.035667.

  PMID: 17401086 BACKGROUND

• Ambrosini V, Campana D, Bodei L, Nanni C, Castellucci P, Allegri V, Montini GC, Tomassetti P, Paganelli G, Fanti S. 68Ga-DOTANOC PET/CT clinical impact in patients with neuroendocrine tumors. J Nucl Med. 2010 May;51(5):669-73. doi: 10.2967/jnumed.109.071712. Epub 2010 Apr 15.

  PMID: 20395323 BACKGROUND

• Versari A, Camellini L, Carlinfante G, Frasoldati A, Nicoli F, Grassi E, Gallo C, Giunta FP, Fraternali A, Salvo D, Asti M, Azzolini F, Iori V, Sassatelli R. Ga-68 DOTATOC PET, endoscopic ultrasonography, and multidetector CT in the diagnosis of duodenopancreatic neuroendocrine tumors: a single-centre retrospective study. Clin Nucl Med. 2010 May;35(5):321-8. doi: 10.1097/RLU.0b013e3181d6677c.

  PMID: 20395703 BACKGROUND

MeSH Terms

Conditions

Neuroendocrine Tumors; Hypersensitivity

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Immune System Diseases

Study Officials

• Lorenzo Camellini, MD

  Gastroenterology and Digestive Endoscopy Unit, Santa Maria Hospital, Reggio Emilia, Italy.

  STUDY DIRECTOR

• Gabriele Carlinfante, MD

  Unit of Pathology, Santa Maria Nuova Hospital, Reggio Emilia, Italy

  STUDY DIRECTOR

• Andrea Frasoldati, MD

  Department of Endocrinology, Thyroid Disease Center-Arcispedale Santa Maria Nuova of Reggio Emilia, Reggio Emilia, Italy.

  STUDY DIRECTOR

• Armando Froio, Biologist

  Nuclear Medicine Unit, Santa Maria Nuova Hospital

  STUDY DIRECTOR

• Tiziana Cassetti, Biologist

  Gastroenterology and Digestive Endoscopy Unit, Santa Maria Hospital, Reggio Emilia, Italy.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2012
• First Posted: August 28, 2012
• Study Start: August 1, 2012
• Primary Completion: August 1, 2015
• Study Completion: July 5, 2016
• Last Updated: June 24, 2025

Record last verified: 2018-03

Locations

IT (20); AU (1)