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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03322592




Registration number
NCT03322592
Ethics application status
Date submitted
19/10/2017
Date registered
26/10/2017
Date last updated
6/02/2019

Titles & IDs
Public title
EUS-FNB With ROSE Vs. EUS-FNB Without ROSE
Scientific title
A Multicenter Randomized Trial, Comparing EUS Fine Needle Biopsy (EUS-FNB) With Rapid On-Site Evaluation (ROSE) Versus EUS-FNB Alone for the Evaluation of Patients With Solid Pancreatic Lesions
Secondary ID [1] 0 0
1481CESC
Universal Trial Number (UTN)
Trial acronym
FROSENOR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Biopsy, Fine-needle 0 0
Pancreatic Neoplasm 0 0
Condition category
Condition code
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Diagnosis / Prognosis - Rapid on-site evaluation (ROSE)
Diagnosis / Prognosis - Histologic evaluation

Active Comparator: EUS-FNB with ROSE - Intervention: Rapid on-site evaluation (ROSE) In the EUS-FNB with ROSE arm, the material obtained with the first pass will be processed for ROSE using the touch imprint technique. The biopsy specimen is carefully pressed onto the slide, allowing the superficial cells to adhere, and then gently lifted with forceps thereby creating a touch imprint of the specimen on the slide. In case of inadequate sample, a second pass will be done and the touch imprint technique will be repeated up to a maximum of 3 passes. In case of adequate ROSE at the first or the second pass, the additional passes will be performed as EUS-FNB and the material obtained placed directly into formalin or other fixative for subsequent histopathological evaluation.

Active Comparator: EUS-FNB without ROSE - Intervention: histologic evaluation In the FNB alone arm, 3 needle passes will be performed and the samples obtained will be placed directly in a vial containing formalin (or other fixative according to the local individual protocol). Macroscopic on-site evaluation (MOSE) of acquired sample will be then performed by the endoscopist.


Diagnosis / Prognosis: Rapid on-site evaluation (ROSE)
On-site evaluation of the acquired samples will be performed by pathologist

Diagnosis / Prognosis: Histologic evaluation
Samples collected in the EUS-FNB without ROSE will be processed as histologic samples

Intervention code [1] 0 0
Diagnosis / Prognosis
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
EUS-FNB diagnostic accuracy - Defined as the ratio between the sum of true positive and true negative values divided by the number of lesions.
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
Procurement yield of tissue "core" - Procurement percentage of a "core" (defined as a piece of tissue at least 550 micron in the greatest axis) in the two arms and using three different needles types.
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
Samples tissue integrity - Tissue integrity will be evaluated by attributing a score from zero to 6 (6 represents the better outcome), according to the following score system:
0=Insufficient material for interpretation. 1=Sufficient material for limited cytological interpretation; probably not representative. 2=Sufficient material for adequate cytological interpretation. 3=Sufficient material for low quality histological interpretation (microfragments < 550 micron in greatest axis). 4=Sufficient material for good quality histological interpretation (1 to 5 cores > 550 micron in greatest axis). 5=Sufficient material for high quality histological interpretation (6 to 10 cores > 550 micron in greatest axis). 6=Sufficient material for excellent quality histological interpretation (more than 10 cores > 550 micron in greatest axis or total tissue length > 5.500 micron).
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
Samples blood contamination - Blood contamination will be evaluated by attributing a score from zero to 3 (3 represents the better outcome), according to the following score system:
0=Only blood. 1=Much blood contamination, surface area > 50 % of the slide. 2=Medium blood contamination, surface area 25-50 % of the slide. 3=Little blood contamination, surface area < 25 % of slide.
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
Time (minutes) of the procedures with and without ROSE - Time of the procedure is defined by the time from the insertion of the needle into the working channel of the echoendoscope for the first pass to the removal of the needle after the third pass
Timepoint [4] 0 0
6 months
Secondary outcome [5] 0 0
Percentage of procedure related adverse events [Safety] - Intra-procedural and post-procedural adverse events in the 2 arms and using three different needle types will be evaluated
Timepoint [5] 0 0
6 months
Secondary outcome [6] 0 0
Macroscopic on-site evaluation [MOSE] - Concordance between presence of a core at Macroscopic on-site evaluation (MOSE) and presence of core at histopathological evaluation, in the EUS-FNB without ROSE arm.
Timepoint [6] 0 0
6 months

Eligibility
Key inclusion criteria
- Solid pancreatic mass referred for EUS-guided tissue acquisition

- Lesion can be visualized with EUS and needle puncturing can be technically feasible

- Written informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known bleeding disorder that cannot be sufficiently corrected with co-fact or fresh
frozen plasma (FFP)

- Use of anticoagulants that cannot be discontinued

- International Normalized Ratio (INR) >1.5 or platelet count <50.000

- Cystic lesions even with solid component

- Previous inclusion in other or present study

- Pregnancy

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Virginia
Country [2] 0 0
Belgium
State/province [2] 0 0
Brussels
Country [3] 0 0
Italy
State/province [3] 0 0
Milano
Country [4] 0 0
Italy
State/province [4] 0 0
Palermo
Country [5] 0 0
Italy
State/province [5] 0 0
Verona
Country [6] 0 0
Japan
State/province [6] 0 0
Tokyo
Country [7] 0 0
Japan
State/province [7] 0 0
Wakayama
Country [8] 0 0
Netherlands
State/province [8] 0 0
Rotterdam
Country [9] 0 0
Spain
State/province [9] 0 0
Barcellona
Country [10] 0 0
Spain
State/province [10] 0 0
Santiago De Compostela
Country [11] 0 0
Sweden
State/province [11] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Other
Name
Azienda Ospedaliera Universitaria Integrata Verona
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Rationale: Rapid on-Site Evaluation (ROSE) of cytologic specimens acquired with EUS-guided
fine needle aspiration (EUS-FNA) represents the most accurate available technique to reach a
definitive diagnosis in patients with pancreatic solid masses. Cytologic interpretation,
however, requires a high degree of expertise rarely found outside high volume centers and
ROSE is not available in many countries. This has created a barrier to the widespread
dissemination of EUS in the community and throughout the world, because the lack of cytologic
expertise has resulted in a low diagnostic accuracy and, therefore, in a limited perceived
utility of EUS. A device that is able to: (i) acquire histologic core biopsy samples usually
easier to be interpreted; (ii) be used by most of the endosonographers and not only by the
experts; (iii) have a performance at least not inferior to ROSE, will represent a major
breakthrough in the field of EUS tissue acquisition. The availability of such needles will
determine a shift from cytology to histology that will overcome some of the limitations of
cytology and ROSE, thus strongly contributing to the diffusion of EUS throughout the world
and in the community.

Objectives: To compare the performance and the diagnostic accuracy of EUS-guided fine needle
biopsy (EUS-FNB) coupled with ROSE with that of EUS-FNB alone using an FNB needle.

Study design: International randomized multicenter trial. Study population: Patients =18
years old, referred for EUS-guided tissue sampling of a solid pancreatic mass.

Intervention: EUS-guided tissue acquisition by means of either EUS-FNB with ROSE or EUS-FNB
alone, using one of the following FNB needles: Procore 20-gauge, SharkCore 22-gauge or
Acquire 22-gauge.

Main study parameters/endpoints: The main endpoint is the diagnostic accuracy, measured
against the gold standard diagnosis that will be surgical resection specimen or in
non-operated patients the results of other diagnostic work-up (other tissue sampling
techniques and imaging studies) or the clinical course of the disease. Secondary endpoints
include: i) safety; ii) presence of tissue core; iii) feasibility to perform additional
immunohistochemical/molecular biology analyses; iv) time of the sampling procedure.
Trial website
https://clinicaltrials.gov/show/NCT03322592
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Stefano Francesco Crinò, MD
Address 0 0
Azienda Ospedaliera Integrata Verona
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Stefano Francesco Crinò, MD
Address 0 0
Country 0 0
Phone 0 0
00390458126169
Fax 0 0
Email 0 0
stefanofrancesco.crino@aovr.veneto.it
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03322592