Clinical trial NCT01673906: 68-Ga-labeled Octreotide Analogues PET in Duodenal-pancreatic Neuroendocrine Tumours
Official title: Accuracy and Clinical Impact of 68-Ga-labeled Octreotide Analogues PET in Diagnosis and Staging of Duodenal-pancreatic Neuroendocrine Tumours; Proposal of a Multicenter, Prospective Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Tumours
Keywords: positron-emission tomography
neuroendocrine tumors
endosonography
tomography, X-ray computed
biopsy, fine needle
sensitivity and sensibility
Lead sponsor: Azienda USL Reggio Emilia - IRCCS
Sponsor class: OTHER_GOV
First posted: 2012-08-28
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: Inclusion Criteria:

1. Patients affected by proved MEN-I, in whom a neoplasm in the duodenal-pancreatic area is suspected.
2. Patients with clinical diagnosis of carcinoid syndrome.
3. Patients with clinical diagnosis of Zollinger-Ellison syndrome.
4. Patients with insulinoma, as proved by fasting test.
5. Patient with clinical pictures and laboratory findings suggesting other functional or non-functional NET.
6. Patients who had previously undergone surgery, including total and subtotal pancreatectomy, or a duodenotomy, intended as curative for a histologically confirmed NET.
7. Patients who were diagnosed with NET metastasis with unknown primary location of the disease.
8. 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.
9. 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.

Exclusion criteria:

1. Patient unwilling, or unable to consent.
2. Pregnancy, or lactation.
3. Age \<18 years
4. Known diagnosis of duodenal-pancreatic NET.
5. Patients with concomitant life-threatening disease.
6. 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.
7. Patients who had previously undergone total gastrectomy or pancreatectomy will be included in the study, but they will not undergo EUS.

Primary outcomes:
measure: Accuracy of the diagnostic test.
timeFrame: one year
measure: Accuracy of the diagnostic test (after exclusion of patients enrolled due to a incidentally diagnosed lesion)
timeFrame: one year
Secondary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety.
timeFrame: one year
measure: Sensitivity of the diagnostic tests.
timeFrame: one year
measure: Specificity of the diagnostic tests.
timeFrame: one year
measure: Clinical impact of PET.
timeFrame: one year
measure: Diameter of lesions.
timeFrame: one year
Other outcomes:
measure: Accuracy of EUS-FNA
timeFrame: one year
Locations:
city: Innsbruck
country: Austria
facility: Irene Virgolini
city: Guastalla
country: Italy
facility: Laura Scaltriti
state: Reggio Emilia
city: Reggio Emilia
country: Italy
facility: ASMN IRCCS Reggio Emilia
state: RE
city: Albano Laziale
country: Italy
facility: Enrico Papini
state: Roma
city: Bologna
country: Italy
facility: Nadia Cremonini
city: Cremona
country: Italy
facility: Fernando Cirillo
city: Genova
country: Italy
facility: Diego Ferone
city: Milano
country: Italy
facility: Giovanna Pepe
city: Modena
country: Italy
facility: Rita Conigliaro
city: Modena
country: Italy
facility: Luppi Gabriele
city: Parma
country: Italy
facility: Pellegrino Crafa
city: Perugia
country: Italy
facility: Piero Ferolla
city: Pisa
country: Italy
facility: Antonio Chella
city: Roma
country: Italy
facility: Roberto Baldelli
city: Roma
country: Italy
facility: Vittoria Rufini
city: Torino
country: Italy
facility: Claudio De Angelis
city: Torino
country: Italy
facility: Marco Gallo
city: Torino
country: Italy
facility: Paolo Limone
city: Udine
country: Italy
facility: Franco Grimaldi
city: Verona
country: Italy
facility: Massimo Falconi
city: Verona
country: Italy
facility: Roberto Castello
Study officials:
affiliation: Gastroenterology and Digestive Endoscopy Unit, Santa Maria Hospital, Reggio Emilia, Italy.
name: Lorenzo Camellini, MD
role: STUDY_DIRECTOR
affiliation: Unit of Pathology, Santa Maria Nuova Hospital, Reggio Emilia, Italy
name: Gabriele Carlinfante, MD
role: STUDY_DIRECTOR
affiliation: Department of Endocrinology, Thyroid Disease Center-Arcispedale Santa Maria Nuova of Reggio Emilia, Reggio Emilia, Italy.
name: Andrea Frasoldati, MD
role: STUDY_DIRECTOR
affiliation: Nuclear Medicine Unit, Santa Maria Nuova Hospital
name: Armando Froio, Biologist
role: STUDY_DIRECTOR
affiliation: Gastroenterology and Digestive Endoscopy Unit, Santa Maria Hospital, Reggio Emilia, Italy.
name: Tiziana Cassetti, Biologist
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.