Clinical Trial Results:
An open-label, single-arm, rater-blinded, multicenter phase 1/2 study to assess safety and diagnostic accuracy and radiotherapeutic implications of pre-operative Ga-68-PSMA-11 PET/CT imaging in comparison to histopathology, in newly-diagnosed prostate cancer (PCA) patients at high risk for metastasis, scheduled for radical prostatectomy (RP) with extended pelvic lymph node dissection (EPLND).
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Summary
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EudraCT number |
2016-001815-19 |
Trial protocol |
DE AT |
Global end of trial date |
03 Jul 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Sep 2022
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First version publication date |
15 Sep 2022
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Other versions |
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Summary report(s) |
Clinical Study Report (Synopse) |
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 |
Ga-68-PSMA-11
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03362359 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Deutsches Krebsforschungszentrum (DKFZ)
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Sponsor organisation address |
Im Neuenheimer Feld 280, Heidelberg, Germany, 69120
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Public contact |
Dr. Julia Ritzerfeld, Deutsches Krebsforschungszentrum (DKFZ)
Clinical Trial Office (M130)
, +49 6221 42-1678, j.ritzerfeld@dkfz.de
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Scientific contact |
Dr Klaus Kopka, Helmholtz-Zentrum Dresden-Rossendorf, +49 351 260 2060, k.kopka@hzdr.de
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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 |
30 Nov 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Jul 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Jul 2020
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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 |
1. To assess the ability of Ga-68-PSMA-11 PET/CT imaging to detect prostate cancer tissue within
a. the prostate gland on level of quadrant (or octant if possible) and
b. pelvic lymph node metastases on level of 8 defined sub-regions.
2. To assess the clinical safety of Ga-68-PSMA-11.
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Protection of trial subjects |
To minimise irradiation of the urinary bladder, subjects will be encouraged to increase fluid intake and to void frequently through the first day after administration.
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Background therapy |
All patients were scheduled for radical prostatectomy (RP) with extended pelvic lymph node dissection (EPLND). | ||
Evidence for comparator |
no comparator used | ||
Actual start date of recruitment |
01 Sep 2017
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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 |
Austria: 3
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Country: Number of subjects enrolled |
Germany: 169
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Country: Number of subjects enrolled |
Switzerland: 1
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Worldwide total number of subjects |
173
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EEA total number of subjects |
172
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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) |
0
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From 65 to 84 years |
173
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited in 9 uro-oncological sites in Germany, Austria, and Switzerland, with access to a radiopharmaceutical laboratory, experienced to prepare 68Ga-labelled compounds, and high-quality PET/CT imaging. | ||||||||||
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Pre-assignment
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Screening details |
Histologically confirmed adenocarcinoma of the prostate. High risk for metastasis, defined by either: a. stadium cT3 according to TNM classification, or b. Gleason Score >7, or c. PSA >20 ng/mL. Patient scheduled for radical prostatectomy (RP) with extended pelvic lymph node dissection (EPLND) according to current guidelines 7–60 days after | ||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Single blind | ||||||||||
Roles blinded |
Assessor [1] | ||||||||||
Blinding implementation details |
Histology analysis were made centrally by a single pathologist blind to imaging results. Conversely, PET/CT (PET/MR) images were analysed by two central readers plus a central adjudication reader blind to histology results.
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Arms
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Arm title
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Single arm study | ||||||||||
Arm description |
Study subjects were not divided into different arms i.e. single arm. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
68Ga-complex of Glu-NH-CO-NHLys-(Ahx)-HBED-CC
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Investigational medicinal product code |
Ga-68-PSMA-11
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Total dose (number and unit): ≤ 6 µg microgram(s)
Route of administration (relevant to the maximum dose): Intravenous use
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| Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: Investigator and subject were unblinded. Only entral assessments of pathology and image data were blinded to each other. |
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
ddd | ||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Single arm study
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Reporting group description |
Study subjects were not divided into different arms i.e. single arm. | ||
Subject analysis set title |
Full analysis
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All patients who were enrolled and were given a treatment number, irrespective of whether or not they received Ga-68-PSMA-11
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Subject analysis set title |
Safety analysis
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All patients who received Ga-68-PSMA-11.
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Subject analysis set title |
Image data set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Also called IDS (= image data set).
All patients who:
• had Ga-68-PSMA-11 PET image data with sufficient technical quality allowing to determine
at least one of the imaging variables (see Section 9.5.8.1)
• underwent the planned RP / EPLND, and
• did not have major protocol deviations
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Subject analysis set title |
Per protocol
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All patients who had data available for the primary variable and did not have major protocol deviations (ICH E9).
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End point title |
Sensitivity and Specificity of 68Ga-PSMA-11 PET/CT Imaging in Detecting Prostate Cancer Tissue Within the Prostate Gland on Level of Patient [1] | ||||||||||
End point description |
The ability of Ga-68-PSMA-11 PET/CT imagining to detect prostate cancer tissue within the prostate
gland was performed per patient . Histopathology results were the reference
for assessment.
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End point type |
Primary
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End point timeframe |
overall trial
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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: We did not succeed at entering the data on statistics given in the CSR into the existing fields of this website |
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Attachments |
14.2.1.1 Sensitivity, Specificity, PPV, NPV And Ac |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Sensitivity and Specificity of 68Ga-PSMA-11 PET/CT Imaging in Detecting Prostate Cancer Tissue Within the Prostate Gland on Level of Quadrant [2] | ||||||||||
End point description |
The ability of Ga-68-PSMA-11 PET/CT imagining to detect prostate cancer tissue within the prostate
gland was performed per quadrant of the prostate gland. Histopathology results were the reference
for assessment
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End point type |
Primary
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End point timeframe |
overall trial
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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: We did not succeed at entering the data on statistics given in the CSR into the existing fields of this website |
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Attachments |
Detection of tracer uptake |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Sensitivity and Specificity of 68Ga-PSMA-11 PET/CT Imaging in detecting Prostate Cancer Tissue within Pelvic Lymph Node Metastases at the Level of 8 defined Sub-regions [3] | ||||||||||
End point description |
Sensitivity and specificity of Ga-68-PSMA-11 PET/CT imaging in detecting prostate cancer tissue
within the pelvic lymph node metastases at the level of 8 defined sub-regions were evaluated. The
evaluation was done at patient, gross-region (pelvic left/right) and sub-region level
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End point type |
Primary
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End point timeframe |
overall trial
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| Notes [3] - 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: We did not succeed at entering the data on statistics given in the CSR into the existing fields of this website |
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Attachments |
pelvic lymph nodes |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Safety [4] | ||||||||
End point description |
Quantity and Severity of Adverse Events
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End point type |
Primary
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End point timeframe |
day0-day7
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| Notes [4] - 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: We did not succeed at entering the data on statistics given in the CSR into the existing fields of this website |
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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 treatment until day 7 (end of study)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.1
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Reporting groups
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Reporting group title |
overall trial
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Reporting group description |
A total of 173 patients received the study treatment within the stipulated dose range and were included in safety analysis. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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24 Mar 2017 |
Only PSMA expression in lymph nodes and not in prostate to be analysed following a 2nd injection of Ga-68-PSMA-11
• Addition of an exclusion criterion of simultaneous participation in other clinical trials
• Increase in number of patients considering a 15% drop out rate
• Redefinition of negative histological result
• Change of study start dates
• Addition of an examination/evaluation
• Removal of categorising of AE assessment as optional
• Detailed information on pharmacovigilance system
• Correction of calculation error related to total volume of blood collected from each patient
• Update of monitoring process |
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05 Jul 2017 |
• Change of study dates
• Correction of radioactivity concentration of the study drug |
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22 Mar 2018 |
• Increase the number of days after start of the study for patients scheduled for RP with EPLND
provided in the current guidelines in the inclusion criteria
• Increase the number of days in the inclusion criteria which the pelvic MRI or CT and 99mTc
bone scintigraphy should be prior to inclusion
• Inclusion of a document name to improve clarity related to histological guidance
• Update of the contact person in the administrative structure (Histology reference laboratory)
• Update of the reference pathologist
• Inclusion of a document name related to histological guidance in sample shipment |
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30 Sep 2019 |
• Increase in the number of days after the start of the study for patients scheduled for RP with EPLND provided in the current guidelines in the inclusion criteria
• To let pelvic MRI or CT be used at the discretion of the investigators in preoperative PCA staging inclusion criteria
• Clarification that central readers to be used and that a central adjudication reader to be involved in case of ambiguous results
• Clarification that if surgery and sampling of tissue specimens is performed after the study as part of standard care, it is to be done between Day 7 (after EOS) and Day 60 after the start of the study.
• Extend the end of recruitment date |
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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 | |||
