Clinical Trial Results:
Accuracy of lymph node imaging in prostate cancer: A prospective cohort study to determine the concordance between two imaging modalities, “Combidex” magnetic resonance imaging (Nano MRI) and 68Ga-PSMA positron emission tomography (PET).
Summary
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EudraCT number |
2015-005016-15 |
Trial protocol |
NL |
Global end of trial date |
30 Oct 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Oct 2024
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First version publication date |
30 Oct 2024
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Other versions |
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 |
NL55589.091.16
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03223064 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Radboudumc
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Sponsor organisation address |
Geert Grooteplein Zuid 10,, Nijmegen, Netherlands,
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Public contact |
Radiology and Nuclear Medicine, Radboudumc, 0031 243615105, trialbureau.radng@radboudumc.nl
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Scientific contact |
Radiology and Nuclear Medicine, Radboudumc, 0031 243615105, trialbureau.radng@radboudumc.nl
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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 |
01 Oct 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Sep 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Oct 2017
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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 |
This study aimed to evaluate the effectiveness of ePLND in removing metastatic LNs in men with primary intermediate and high-risk prostate cancer and assess the value of nMRI and PSMA-PET/CT in detecting small metastatic LNs.
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Protection of trial subjects |
Both 68 Ga-PSMA-PET/CT and Nano-MR Lymphography (Ferumoxtran-10) have been used for over 5 years for the detection of metastases in patients with prostate cancer at intermediate to high risk. Pelvic Lymph Node Dissection and image directed dissection can be considered as the gold standard for such patients. All patients received both imaging modalities by 2 experienced (> 5 years experience) radiologists (nMRI) and four experienced (> 5 years experience) nuclear medicine physicians (68 Ga-PSMA-PET/CT). The standard imaging protocol within the hospital was used including patient and physician safety measures. Similarly for Pelvic Lymphnode dissection (PLND), the standard surgical protocol was used within the hospital with its patient and physician safety measures. Pelvic Lymphnode dissection was performed by an experienced surgeon (> 20 years) with the outcome of the nMRI and 68 Ga-PSMA-PET/CT imaging procedures. If suspicious lymphnodes on pre-operative imaging were also visible on postoperative MRI (six weeks after PLND) these were considered as not removed by PNLD. Positive LNs on preoperative nMRI and/or 68 Ga-PSMA-PET/CT were re-identified on postoperative MRI based on location, size and shape. The protocol was approved by the local institution review boards (NL55589.091.16).
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Background therapy |
Extended lymph node dissection (ePLND) is the current reference-standard for nodal (N)-staging and should be performed in men with prostate cancer (PCa) and >5% risk of lymph node metastases (LNMs) according to the European Association of Urology (EAU) guidelines. | ||
Evidence for comparator |
Conventional imaging techniques such as CT and MRI rely on lymph node (LN) size and morphology and therefore are of limited value. Two new molecular imaging techniques have demonstrated their ability to detect small LNMetastases (LNMs), combined with high specificity. These are nano-(n)MRI, which uses ultra-small iron oxide particles as contrast agent (ferumoxtran-10, Ferrotran®, SPL-Medical, Nijmegen, The Netherlands) and 68Ga PSMA-HBED-CC PET/CT (PSMA-PET/CT). With nMRI, very small LNMs can be detected with high sensitivity (91%). PSMA-PET/CT uses radio-labelled tracers that target the PSMA receptors which are overexpressed in prostate cancer cells. This enables total-body body imaging of LNMs and other metastases. Both techniques have the potential to improve N-staging and could be valuable tools to complement PLND. However, validation studies using PLND as a reference-standard are scarce and show high differences in sensitivity and specificity. Most studies are limited by the abscence of postoperative imaging to verify whether LNMs are removed. They also lack detailed histological validation on a node-by-node or regional basis and follow-up. Nevertheless, initial retrospective comparison of PSMA-PET/CT and nMRI has shown that both are able to identify small suspicious LNs in all anatomical regions of the pelvis, with nMRI detecting more and smaller suspicious LNs. However, a prospective validation study is needed to compare the diagnostic performance of PSMA-PET/CT and nMRI. | ||
Actual start date of recruitment |
01 Apr 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Netherlands: 42
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Worldwide total number of subjects |
42
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EEA total number of subjects |
42
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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) |
22
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From 65 to 84 years |
20
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85 years and over |
0
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Recruitment
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Recruitment details |
Forty-two men with newly diagnosed PCa and an estimated risk of metastatic LNs exceeding 5%, based on the Memorial Sloan Kettering Cancer Center nomogram (https://www.mskcc.org/nomograms/prostate/pre_op), were included in the study. These men underwent a nMRI and a 68Ga PSMA-HBED-CC PET/CT (PSMA-PET/CT) scan. | ||||||
Pre-assignment
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Screening details |
42 Patients were included after giving verbal and written informed consent. | ||||||
Pre-assignment period milestones
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Number of subjects started |
42 | ||||||
Number of subjects completed |
42 | ||||||
Period 1
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Period 1 title |
nano-MRI and PLND and PSMA-PET-CT (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Blinding implementation details |
No Blinding implementation details
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Arms
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Arm title
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Nano-MRI and PSMA-PET-CT and PLND | ||||||
Arm description |
Patients with nano-MRI, PSMA-PET/CT and PLND | ||||||
Arm type |
1-arm study | ||||||
Investigational medicinal product name |
ferumoxtran
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solvent for parenteral use
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Routes of administration |
Intravenous use
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Dosage and administration details |
(2.6 mg/kg body weight
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Investigational medicinal product name |
PSMA-PET-CT
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
2 MBq/kg body weight
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Baseline characteristics reporting groups
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Reporting group title |
nano-MRI and PLND and PSMA-PET-CT
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Per Protocol Analysis
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
38 Patients received all study procedures and are included in the final analysis
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End points reporting groups
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Reporting group title |
Nano-MRI and PSMA-PET-CT and PLND
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Reporting group description |
Patients with nano-MRI, PSMA-PET/CT and PLND | ||
Subject analysis set title |
Per Protocol Analysis
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
38 Patients received all study procedures and are included in the final analysis
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End point title |
Correlation ePLND with postoperative MRI [1] | ||||||
End point description |
On the postoperative MRI 60 of the 74 (81%) nMRI-positive LNs and 23 of the 29 (79%) PSMA-PET/CT-positive LNs were still present. On a per-patient level, this was 17 of the 29 (59%) men for nMRI and 13 of the 19 (68%) for PSMA-PET/CT. No LNs with positive findings on imaging were extracted from the para-aortic, common iliac, presacral, and para-rectal regions. The largest number of LNs with suspected positive findings on imaging were removed from the external iliac region (48%).
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End point type |
Primary
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End point timeframe |
6 weeks
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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: Simple comparative statistics was used. |
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No statistical analyses for this end point |
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End point title |
Histopathologic results [2] | ||||||
End point description |
Among the 38 men analyzed, 13 (34%) had histopathological confirmed metastatic LN. Of the 915 resected LNs, 22 (2.4%) contained metastasis with a median size of 3 mm (range 2-18 mm). Fifteen (68%) of these metastatic LNs were smaller than 4 mm. Nano-MRI identified 13 out of 22 lymph nodes as true positives (TP), 1 as false positive (FP), and missed 9 as false negatives (FN; Table 2). Among the 13 correctly identified LNs, 5 were larger than 5mm, 6 ranged from 2-5mm, and 2 were smaller than 2mm. The PSMA-PET/CT examination revealed 6 out of 22 (27%) true positive LNs, 1 out of 22 (4.5%) false positive LN, and 16 out of 22 (73%) false negative LNs. Among these, 6 out of 22 LNs were metastatic, with 4 being larger than 5 mm, 1 between 2 to 5 mm, and 1 smaller than 2 mm. At the patient level, nMRI identified 1 out of 13 (8%) false negative patients, while PSMA-PET/CT identified 7 out of 13 (54%) false negative patients.
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End point type |
Primary
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End point timeframe |
4 weeks
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Notes [2] - 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: Simple comparative statistics was used. |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
from 2016-2017
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Adverse event reporting additional description |
No adverse events
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Assessment type |
Non-systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
LAREB | ||
Dictionary version |
1
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Frequency threshold for reporting non-serious adverse events: 0.1% | |||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: To our knowledge there were no adverse events reported |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
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. | |||
A major limitation of the study is the presence of a high number of non-removed, preoperatively suspected LNs on imaging, which hinders the validation of the diagnostic accuracy of both imaging methods using histopathology as the reference standard. |