|- candidate number||28301|
|- NTR Number||NTR6862|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||5-dec-2017|
|- Secondary IDs||EudraCT 2016-002485-31 ABR- nummer 58936.042.16|
|- Public Title||Optimisation of [68Ga] PSMA-11 PET/CT Imaging Protocol for localizing primary prostate cancer prior to radical prostatectomy |
|- Scientific Title||Optimisation of PSMA PET/CT protocol for primary prostate cancer|
|- hypothesis||The primary objectives are to determine the optimal pharmacokinetic model of 68Ga-PSMA PET/CT, so 68Ga-PSMA PET/CT results can be quantified in prostate cancer and to determine whether the optimal kinetic model of 68Ga-PSMA PET/CT is valid (by a repeatability test) and the secondary objective is to see if 68Ga-PSMA PET/CT could be a feasible method to exactly localize the tumour within the prostate.|
|- Healt Condition(s) or Problem(s) studied||Prostate cancer|
|- Inclusion criteria||• Male aged 18 years or older |
• Ability to provide signed informed consent and willingness to comply with protocol requirements.
• Biopsy confirmed presence of adenocarcinoma of the prostate gland
• Planned/already executed mpMRI (standard of care).
• Planned for radical prostatectomy (standard of care).
|- Exclusion criteria||• Have any medical condition or other circumstances that, in the opinion of the investigator, would significantly decrease obtaining reliable data, achieving study objectives, or completing the study. (part A and B)|
• Have a contraindication for mpMRI. (part A and B)
• Will not undergo a radical prostatectomy. (part A and B)
• Claustrophobia (part A and B)
• Multiple malignancies (part A and B)
• Anticoagulant therapy (part A)
• Obese (>120 kg) (part A)
• Have undergone a transurethral resection of prostate in the past (part A and B)
|- mec approval received||yes|
|- multicenter trial||no|
|- planned startdate ||20-dec-2017|
|- planned closingdate||1-jul-2019|
|- Target number of participants||20|
|- Interventions||Not applicable, the study design is: A monocenter, prospective observational study in 20 patients with primary prostate cancer. The study consists of two parts: part A, to determine the tracer kinetic properties and the optimal pharmacokinetic model to quantify and identify 68Ga-PSMA uptake, to assess which (perfusion independent) pharmacokinetic parameter best reflects presence of tumour and to validate simplified (quantitative) metrics that can be used in a clinical setting. The optimal kinetic model and quantitative analysis will be validated in a test-retest setting used in part B. In both study parts, data will be used to determine whether 68Ga-PSMA is feasible to exactly and repeatedly localize the tumour within the prostate, prior to radical prostatectomy. Patients participate in either part A or part B, never both.
A. In the first part, both PSMA (68Ga-PSMA) uptake and perfusion (H215O) will be measured quantitatively. Eight patients will be injected with two tracers: H215O and 68Ga-PSMA followed by dynamic scans of one bed position, namely the pelvis. Accuracy of blood and plasma activity concentrations, plasma metabolite measurements derived from arterial and venous samples as well the reliability of using Image Derived Input Functions (IDIF) for quantification of 68Ga-PSMA kinetics will be tested. |
B. In the second step of the protocol, depending on the obtained validation in part A, the clinically feasible imaging procedure will be used in 12 other patients, e.g. using a simplified 68Ga-PSMA PET-CT imaging study. Repeat PSMA PET/CT scanning will be performed in these 12 patients, to do a test-retest study on tumor tracer uptake and localization.
|- Primary outcome||To establish the ideal timing of performing the WB 68Ga-PSMA PET after administration of the radiotracer and to determine the optimal (quantitative) pharmacokinetic model for describing 68Ga-PSMA uptake (Part A).|
To study test-retest characteristics of 68Ga PSMA PET (Part B).
|- Secondary outcome||- To determine whether it is feasible to exactly identify and localize the tumour within the prostate with PSMA PET/CT(Part A and B).|
- Comparison of 68Ga-PSMA PET (study visit) versus mpMRI (standard of care) regarding to tumour localization within the prostate.
|- Timepoints||Patients participating in the study will need to undergo their 68Ga-PSMA PET +/- H215O PET scan before the clinically performed radical prostatectomy. Preferably, the first 68Ga-PSMA PET scan is performed within one week from the routinely performed mpMRI (maximal 3 weeks apart)|
The 68Ga PSMA PET is not blinded for the treating physician and patient.
In case of contradictional or coincidental findings on the experimental 68Ga-PSMA PET;
- If MRI shows no extraprostatic growth, but the 68Ga-PSMA PET does, then a prostatectomy will be performed as standard of care.
- If MRI shows extraprostatic growth, regardless of the 68Ga-PSMA PET findings, there will be acted upon standard of care (no prostatectomy will be performed).
- If MRI shows no lymph node metastases in the pelvic area, but the 68Ga-PSMA PET shows a suspicious lesion, the concerning lymph node(s) will be resected according to the judgements of the urologist performing the prostatectomy.
- If MRI shows lymph node metastases in the pelvic area, regardless of the 68Ga-PSMA PET findings, there will be acted upon according to standard of care.
- If the 68Ga-PSMA PET shows coincidental findings outside the pelvic area, for example a suspicious lung lesion, the referring physician will be informed. Confirmation of the finding will be sought and treatment will be according to the findings.
- Drop outs will be replaced in part A of the study. Not in part B.
|- Trial web site||not applicable|
|- CONTACT FOR PUBLIC QUERIES||Mw. dr. MD PhD A.H. Brouwers|
|- CONTACT for SCIENTIFIC QUERIES||Mw. dr. MD PhD A.H. Brouwers|
|- Sponsor/Initiator ||University Medical Center Groningen (UMCG)|
(Source(s) of Monetary or Material Support)
|University Medical Center Groningen (UMCG)|
|- Publications||not applicable|
|- Brief summary||Prostate Specific Membrane Antigen (PSMA) is a epithelial cell surface trans-membrane protein. It is overexpressed in prostate cancer, but is also present in normal prostate cells, kidney, liver, salivary glands and upper large intestine1. This protein can be labelled to different radionuclides, but most experience has been gathered with Gallium-68 (68Ga). The PSMA-inhibitor Glu-NH-CO-NHLys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA-11) was developed by the group of Afshar-Oromieh et al. in Heidelberg. Numerous studies in recurrent prostate cancer showed that PSMA PET/CT is superior to an older phospholipid derivate used in molecular imaging of prostate cancer; choline PET/CT2-4. Although the first studies on PSMA PET/CT focused on recurrent prostate cancer, PSMA PET/CT(or MRI) is currently also used and studied in primary prostate cancer, with encouraging results5-9. There are a lot of treatment methods available for patients with prostate cancer, ideally we would be able to monitor treatment response. Because PET/CT images both in vivo anatomical and metabolic information it can be the ideal imaging bio-marker. To serve as a biomarker, 68 Ga-PSMA PET/CT results have to be quantified. The primary goal of this study is to find the optimal model that fits the pharmacokinetics of 68 Ga-PSMA-11 PET/CT, so that simplified quantification methods can be found. It is important to validate simplified quantification mehods, as there is need to monitor disease and treatment response in-vivo, without invasive treatment, to make a tailored individualized therapy approach possible in prostate cancer. The validity and repeatability of the simplified quantification method will then be tested as secondary aim of this study. Because this study will be performed in patients who will undergo prostatectomy, we will also be able to compare the properties of 68 Ga-PSMA PET/CT to localize intraprostatetic cancer lesions to the current standard, multi-parameter Magnetic Resonance Imaging (mpMRI). According to a recent meta-analysis, MRI has a high specificity for localizing primary prostate cancer10. However, a relative poor sensitivity was shown, especially for extrapostatic growth. |
|- Main changes (audit trail)|
|- RECORD||5-dec-2017 - 11-jan-2018|