Clinical Trial Results:
Diagnostic accuracy of MRI, diffusion-weighted MRI, FDG-PET/CT and Fluoro-ethyl-choline PET/CT in the detection of lymph node metastases in surgically staged endometrial and cervical carcinoma
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Summary
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EudraCT number |
2011-001290-78 |
Trial protocol |
GB |
Global end of trial date |
06 Dec 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Jan 2021
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First version publication date |
02 Jan 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
007697
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Additional study identifiers
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ISRCTN number |
ISRCTN84527805 | ||
US NCT number |
NCT01836484 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Barts Health NHS Trust
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Sponsor organisation address |
5 Walden Street, London, United Kingdom, E1 2EF
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Public contact |
Prof. Andrea Rockall, Imperial College London, 0044 020 7589 5111, a.rockall@imperial.ac.uk
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Scientific contact |
Prof. Andrea Rockall, Imperial College London, 0044 020 7589 5111, a.rockall@imperial.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 Oct 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Dec 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Dec 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
In patients with cancer of the womb (endometrial and cervical cancer), the detection of tumour in adjacent lymph glands (nodes) is very important for optimal treatment planning. Currently the standard method used to identify cancerous spread is to surgically remove and examine the nodes under the micrscope in order to identify tumour spread in the nodes. A technique that does not require surgical intervention would be highly desirable. Standard imaging on MRI or CT, in which size criteria are used to identify whether a node is malignant, is inaccurate.
This study will evaluate three new imaging techniques that may be used to identify malignant nodes preoperatively: (1) Diffusion Weighted MRI, (2) FDG-PET/CT and (3) FEC-PET/CT. The primary objective is to compare the diagnostic performance of each test (detection and false-positive rates) with that of the standard method (size criteria) with histology as the reference standard.
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Protection of trial subjects |
Eligibility criteria for this study were selected to enhance the safety of patients in this trial. Patients were monitored for adverse events during their participation in the trial. Any serious adverse events were recorded until 28 days after the last administration of the PET tracer. A Data Monitoring Committee was appointed to monitor safety during the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Jun 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 162
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Worldwide total number of subjects |
162
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EEA total number of subjects |
162
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
86
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From 65 to 84 years |
76
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85 years and over |
0
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Recruitment
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Recruitment details |
Women with histologically confirmed endometrial or cervical carcinoma who complied with the study entry criteria were recruited at six centres in the UK between 06Jun2012 and 27Jul2017. | ||||||||||||
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Pre-assignment
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Screening details |
162 patients were registered for the trial of which 150 were found to be eligible. | ||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Are arms mutually exclusive |
No
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Arm title
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DW-MRI - primary reference standard | ||||||||||||
Arm description |
The primary reference standard includes all eligible patients who underwent both DW-MRI and FDG-PET/CT and had nodal histology obtained by lymphadenectomy. | ||||||||||||
Arm type |
Imaging technique (no IMP) | ||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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FDG-PET/CT - primary reference standard | ||||||||||||
Arm description |
The primary reference standard includes all eligible patients who underwent both DW-MRI and FDG-PET/CT and had nodal histology obtained by lymphadenectomy | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Fluorodeoxyglucose (FDG)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Administered prior to PET/CT scan with activity of 18F-FDG between 200MBq and 400MBq, +/- 10% of the local diagnostic reference level based on scanner performance and patient body weight.
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Arm title
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FEC-PET/CT - primary reference standard | ||||||||||||
Arm description |
The primary reference standard includes all eligible patients who underwent both DW-MRI and FDG-PET/CT and had nodal histology obtained by lymphadenectomy | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Fluoro-ethyl-choline (FEC)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Administered prior to PET/CT scan with activity of 18F-FEC between 200MBq and 300MBq, +/- 10% of the local diagnostic reference level based on scanner performance and patient body weight.
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Baseline characteristics reporting groups [1]
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Reporting group title |
DW-MRI - primary reference standard
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Reporting group description |
The primary reference standard includes all eligible patients who underwent both DW-MRI and FDG-PET/CT and had nodal histology obtained by lymphadenectomy. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
FDG-PET/CT - primary reference standard
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Reporting group description |
The primary reference standard includes all eligible patients who underwent both DW-MRI and FDG-PET/CT and had nodal histology obtained by lymphadenectomy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
FEC-PET/CT - primary reference standard
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Reporting group description |
The primary reference standard includes all eligible patients who underwent both DW-MRI and FDG-PET/CT and had nodal histology obtained by lymphadenectomy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same. Justification: The primary analysis of this data is based on the subset of patients who are assessable by the primary reference standard. This is all patients who underwent both DW-MRI and FDG-PET/CT imaging and had definitive histology obtained by lymphadenectomy. Data is presented for patients in the subset. |
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End points reporting groups
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Reporting group title |
DW-MRI - primary reference standard
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Reporting group description |
The primary reference standard includes all eligible patients who underwent both DW-MRI and FDG-PET/CT and had nodal histology obtained by lymphadenectomy. | ||
Reporting group title |
FDG-PET/CT - primary reference standard
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Reporting group description |
The primary reference standard includes all eligible patients who underwent both DW-MRI and FDG-PET/CT and had nodal histology obtained by lymphadenectomy | ||
Reporting group title |
FEC-PET/CT - primary reference standard
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Reporting group description |
The primary reference standard includes all eligible patients who underwent both DW-MRI and FDG-PET/CT and had nodal histology obtained by lymphadenectomy | ||
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End point title |
Comparing sensitivity of imaging techniques with nodal size [1] | ||||||||||||||||||||||||||||
End point description |
Sensitivity and false-positive rates for each imaging technique were calculated using strictly confirmed nodal histology as the reference standard. By specifying a cut-off value for diagnosis based on nodal size that matched the false-positive rate of each imaging technique, we could compare the sensitivity of each imaging technique with nodal size while assuming them to have equal false-positive rates.
For each imaging technique assessed, the nodal size cut-off which provided a false-positive rate closest to the imaging technique was >10mm.
Paired comparisons of sensitivity were performed only in patients with confirmed positive histology.
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End point type |
Primary
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End point timeframe |
Each patient underwent imaging before having lymphadenectomy.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: McNemar p-values from comparing sensitivity of each imaging technique with nodal size (10mm cut-off) are as follows: DW-MRI - p=0.22 FDG-PET/CT - p=0.017 FEC-PET/CT - p=0.13 |
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| Notes [2] - Only patients with confirmed positive histology included in this analysis. [3] - Only patients with confirmed positive histology included in this analysis. [4] - Only patients with confirmed positive histology included in this analysis. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the day of consent until 28 days after the last administration of the PET tracer.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
All patients who received any trial scan
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Date |
Amendment |
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12 Apr 2012 |
Change in Sponsor name to Barts Health NHS Trust |
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30 Aug 2012 |
Removal of quality of life objective.
Updates to image analysis scale.
Inclusion of tissue banking of lymph nodes. |
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17 Jun 2013 |
Inclusion criteria clarification.
Update to Informed Consent Procedures.
Update to Enrolment Procedures.
Inclusion of the dynamic FEC-PET/CT protocol.
Removal of FEC safety assessment.
Tissue banking made optional for sites to take part.
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01 May 2014 |
PET tracer doses: incorporation of +/- 10% diagnostic reference level (DRL).
NCRI PET – sending scans for central review instructions update (appendix).
Tissue banking – addition of primary tissue as well as lymph nodes.
SAE reporting clarification.
IMP clarifications. |
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31 Oct 2017 |
Allowing post-surgical imaging review without obtaining further consent in patients with positive imaging and negative histology and patients for whom histology was not performed but all mandatory imaging was done. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
