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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Arcispedale Santa Maria Nuova-IRCCS
Sponsor:
Information provided by (Responsible Party):
Annibale Versari, Arcispedale Santa Maria Nuova-IRCCS
ClinicalTrials.gov Identifier:
NCT01673906
First received: August 9, 2012
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Neuroendocrine Tumours
Drug: Diagnostic work up
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
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

Resource links provided by NLM:


Further study details as provided by Arcispedale Santa Maria Nuova-IRCCS:

Primary Outcome Measures:
  • Accuracy of the diagnostic test. [ Time Frame: one year ] [ Designated as safety issue: No ]
    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.

  • Accuracy of the diagnostic test (after exclusion of patients enrolled due to a incidentally diagnosed lesion) [ Time Frame: one year ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety. [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    Number of patients with adverse events of each procedure: PET, MDCT, endoscopic ultrasonography-fine needle aspiration (EUS-FNA)

  • Sensitivity of the diagnostic tests. [ Time Frame: one year ] [ Designated as safety issue: No ]
    Sensitivity (Number of true positive results/number of true positive + false negative results) of the diagnostic tests in the diagnosis of primary duodenal-pancreatic NET. Sensitivity of each diagnostic test (MDCT, PET, EUS) will be calculated separately on patient (number of true affected patients/number of true affected + number of false non affected patients) and on lesion basis (number of true positive lesions/number of true positive + false positive lesions)with its 95% confidence interval based on normal approximation.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.

  • Specificity of the diagnostic tests. [ Time Frame: one year ] [ Designated as safety issue: No ]
    Specificity (Number of true negative results/number of true negative + false positive results) of the diagnostic tests in the diagnosis of primary duodenal-pancreatic NET. Specificity of each diagnostic test (MDCT, PET, EUS) will be calculated separately on patient (number of true non affected patients/number of true non affected + number of false affected patients) and on lesion basis (number of true negative lesions/number of true negative positive + false positive lesions)with its 95% confidence interval based on normal approximation.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.

  • Clinical impact of PET. [ Time Frame: one year ] [ Designated as safety issue: No ]
    Changes in management plan in consequence of PET results. Prior to receiving the results of the PET scans, the referring clinician will be required to explicit a management plan for the patient. Following the release of the PET results, a second management plan will be recorded, including any changes resulting from the PET findings. The number of patients with changes in their management plan will be recorded.

  • Diameter of lesions. [ Time Frame: one year ] [ Designated as safety issue: No ]
    Median diameter (cm) and ranges of lesions diagnosed by each technique will be calculated.


Other Outcome Measures:
  • Accuracy of EUS-FNA [ Time Frame: one year ] [ Designated as safety issue: No ]
    Accuracy was computed as: (number of true positives + true negatives)/(number + true positives + true negatives + false positives + false negatives). Reference standard will be considered the diagnoses of primary NET, when supported by histology or by at least one year of follow up.


Estimated Enrollment: 142
Study Start Date: August 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Diagnostic work up
The patients enrolled in the study (see below), with a consistent clinical suspicion of a primary duodenal-pancreatic NET.
Drug: Diagnostic work up
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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01673906

Contacts
Contact: Annibale Versari, MD +390522296313 annibale.versari@asmn.re.it

Locations
Austria
Irene Virgolini Not yet recruiting
Innsbruck, Austria
Contact: Irene Virgolini, MD         
Principal Investigator: Irene Virgolini, MD         
Italy
Federica Matteucci Not yet recruiting
Forlì, Meldola, Italy
Contact: Federica Matteucci, MD         
Principal Investigator: Federica Matteucci, MD         
Laura Scaltriti Recruiting
Guastalla, Reggio Emilia, Italy, 42100
Contact: Laura Scaltriti, MD       laura.scaltriti@ausl.re.it   
Principal Investigator: Laura Scaltriti, MD         
ASMN IRCCS Reggio Emilia Recruiting
Reggio Emilia, RE, Italy, 42100
Contact: Annibale Versari, MD         
Principal Investigator: Annibale Versari, MD         
Enrico Papini Not yet recruiting
Albano Laziale, Roma, Italy
Contact: Enrico Papini, MD         
Principal Investigator: Enrico Papini, MD         
Paola Tomassetti Withdrawn
Bologna, Italy
Nadia Cremonini Recruiting
Bologna, Italy
Contact: Nadia Cremonini, MD       nadia.cremonini@ausl.bo.it   
Principal Investigator: Nadia Cremonini, MD         
Fernando Cirillo Not yet recruiting
Cremona, Italy
Contact: Fernando Cirillo, MD         
Principal Investigator: Fernando Cirillo, MD         
Diego Ferone Recruiting
Genova, Italy
Contact: Diego Ferone, MD         
Principal Investigator: Diego Ferone, MD         
Giovanna Pepe Not yet recruiting
Milano, Italy
Contact: Giovanna Pepe, MD         
Principal Investigator: Giovanna Pepe, MD         
Rita Conigliaro Active, not recruiting
Modena, Italy, 41121
Luppi Gabriele Active, not recruiting
Modena, Italy
Pellegrino Crafa Active, not recruiting
Parma, Italy, 43121
Piero Ferolla Not yet recruiting
Perugia, Italy
Contact: Piero Ferolla, MD         
Principal Investigator: Piero Ferolla, MD         
Antonio Chella Not yet recruiting
Pisa, Italy
Contact: Antonio Chella, MD         
Principal Investigator: Antonio Chella, MD         
Roberto Baldelli Active, not recruiting
Roma, Italy
Vittoria Rufini Recruiting
Roma, Italy
Contact: Paolo Limone, MD         
Principal Investigator: Paolo Limone, MD         
Claudio De Angelis Not yet recruiting
Torino, Italy
Contact: Claudio De Angelis, MD         
Principal Investigator: Claudio De Angelis, MD         
Marco Gallo Active, not recruiting
Torino, Italy
Paolo Limone Recruiting
Torino, Italy
Contact: Paolo Limone, MD         
Principal Investigator: Paolo Limone, MD         
Franco Grimaldi Active, not recruiting
Udine, Italy
Roberto Castello Not yet recruiting
Verona, Italy
Contact: Roberto Castello, MD         
Principal Investigator: Roberto Castello, MD         
Massimo Falconi Active, not recruiting
Verona, Italy
Sponsors and Collaborators
Arcispedale Santa Maria Nuova-IRCCS
Investigators
Study Director: 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.
  More Information

Publications:
Responsible Party: Annibale Versari, Director of Nuclear Medicine Department, Arcispedale Santa Maria Nuova-IRCCS
ClinicalTrials.gov Identifier: NCT01673906     History of Changes
Other Study ID Numbers: 2012-000994-22, 2012-000994-22
Study First Received: August 9, 2012
Last Updated: July 1, 2014
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Arcispedale Santa Maria Nuova-IRCCS:
positron-emission tomography
neuroendocrine tumors
endosonography
tomography, X-ray computed
biopsy, fine needle
sensitivity and sensibility

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Neoplasms, Glandular and Epithelial
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Pancreatic Diseases
Adenoma, Islet Cell
Adenoma
Digestive System Diseases
Endocrine System Diseases
Octreotide
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 27, 2014