Clinical Trial Results:
"An exploratory study regarding the use of the biomarker DAT for image diagnosis of clear cell renal cell carcinoma"
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Summary
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EudraCT number |
2016-005182-31 |
Trial protocol |
SE |
Global end of trial date |
04 Jul 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Nov 2018
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First version publication date |
14 Nov 2018
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Other versions |
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Summary report(s) |
Synopsis |
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 |
RCCSCAN
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03185182 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Lund University
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Sponsor organisation address |
Scheelevägen 8, Lund, Sweden,
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Public contact |
Håkan Axelson, Lund University, +46 0462226434, hakan.axelson@med.lu.se
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Scientific contact |
Håkan Axelson, Lund University, +46 0462226434, hakan.axelson@med.lu.se
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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 |
18 Oct 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Jul 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Jul 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 |
The main objective is to investigate whether DaTSCAN with subsequent SPECT can detect elevated DAT levels in at least a lesion identified with CT in patients with clear cell renal cell carcinoma, as assesed by pathologist?
DaTSCAN signal will be seen as positive, displaying intensity ≥3ggr higher than the background and correlating anatomically with at least one lesion found with CT.
DaTSCAN is used routinely to detect the loss of dopaminergic neurons in the striatum of patients with clinically uncertain Parkinsonian Syndromes. The active substance in DaTSCAN, Ioflupane specifically binds to DAT. By analyzing the focal uptake of Ioflupane (123I) with SPECT / CT the progression of the disease may be clarified. In light of our findings that clear cell renal cancer express significantly elevated levels of DAT, we postulate that DaTSCAN can be used for detection of clear cell renal cell carcinoma.
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Protection of trial subjects |
Very few adverse effects are reported for DatSCAN use. In this study we used the same dose and route of administration as is praxis for DaTSCAN when used for diagnostic investigation of Parkinsons disease . Al beit uncommon, pain at the injection site has been previously reported when the solution was injected into a small vain. To minimise the potential for pain at the injection site during administration in this study, a slow intravenous injection (not less than 15 to 20 seconds) via an arm vein was therefore applied. The injections were performed by routined staff at Skåne University Hospital, Department of Clinical Physiology / Nuclear Medicine in Malmö, where usual clinical preparedness for allergic reactions after injection was available.
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Background therapy |
Patients underwent appropriate thyroid blocking treatment prior to injection of DaTSCAN, to minimise thyroid uptake of radioactive iodine. In this study, this was achieved by oral administration of 2x 65 mg potassium iodide tablettes on the night before the DaTSCAN investigation and another 2x 65 mg potassium iodine tabletts 1 hour prior to injection of DaTSCAN. | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
14 Jul 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 |
Sweden: 5
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Worldwide total number of subjects |
5
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EEA total number of subjects |
5
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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) |
4
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited continously in this study. Five patients were recruited, all at the Urological Clinic at Skåne University Hospital, Jan Waldenströms gata 7, 205 02 Malmö, Sweden. The first patient was recruited 2017-07-14 and the last patient was recruited at 2018-05-23. | ||||||||
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Pre-assignment
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Screening details |
Patients were recruited continously in this study. Screening critera: suspected dissiminated renal cancer, age 18-70. Five patients were screened for the study and all five patients were considered suitable for enrollment. | ||||||||
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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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Arm title
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Study population | ||||||||
Arm description |
This is a exploratory open single arm trial, including a small number of patients with suspected disseminated renal cell carcinoma. The objective of the trial is to investigate whether DaTSCAN with subsequent SPECT can be used for detection of clear cell renal cell carcinoma (ccRCC) tumors. Recruited patients with suspected disseminated kidney cancer will, after informed consent to participate in the study, be examined using CT and DaTSCAN followed by SPECT. DaTSCAN is injected intravenously and followed by SPECT examination 5h later. The images from the DaTSCAN investigation will be analyzed and anatomically compared to CT-scan from the same the patient. Any adverse effects during the study will be reported. | ||||||||
Arm type |
Experimental | ||||||||
Investigational medicinal product name |
DaTSCAN
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Investigational medicinal product code |
PR1
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Other name |
Ioflupane (I123)
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Pharmaceutical forms |
Injection, Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
A one time dose is given via intravenous injection of 185 MBq.
The patient takes potassium iodine tablets prior to the DatSCAN injection to protect the thyroid gland. At the time of the DaTSCAN examination, the patient is injected intravenously at slow rate with 185MBq DaTSCAN solution.
With the help of activity gauge, the responsible nurse draws the right amount of DaTSCAN, 185MBq, into the syringe to be given to the subject. The exact time is recorded and specified in the label machine. The label is printed and put on the syringe with the following information: patient name, drug, batch, dose and draw time. Thereafter, the drug is administered directly to the patient. Afterwards, the remaining activity in the syringe is measured and the exact dose is recorded in the patient's journal.
The patient then waits for 5h before diagnostic examination with SPECT.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
All included subjects in the study, which comply with the inclusion and exclusion criteria | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
subjects with verified ccRCC
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Included subjects with pathologically verified clear cell renal cell carcinoma ccRCC
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Subject analysis set title |
Subjects with non-ccRCC
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Subject analysis set type |
Sub-group analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subjects included in the study that were not of the clear cell subtype, according to pathological assessment
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End points reporting groups
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Reporting group title |
Study population
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Reporting group description |
This is a exploratory open single arm trial, including a small number of patients with suspected disseminated renal cell carcinoma. The objective of the trial is to investigate whether DaTSCAN with subsequent SPECT can be used for detection of clear cell renal cell carcinoma (ccRCC) tumors. Recruited patients with suspected disseminated kidney cancer will, after informed consent to participate in the study, be examined using CT and DaTSCAN followed by SPECT. DaTSCAN is injected intravenously and followed by SPECT examination 5h later. The images from the DaTSCAN investigation will be analyzed and anatomically compared to CT-scan from the same the patient. Any adverse effects during the study will be reported. | ||
Subject analysis set title |
subjects with verified ccRCC
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Included subjects with pathologically verified clear cell renal cell carcinoma ccRCC
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Subject analysis set title |
Subjects with non-ccRCC
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects included in the study that were not of the clear cell subtype, according to pathological assessment
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End point title |
Proportion of subjects with pathologically verified ccRCC wich displayed positive DaTSCAN signal in at least one of the lesions identified with CT [1] | ||||||||||||||||||||||||
End point description |
Proportion of subjects with pathologically verified clear cell renal cell carcinoma (ccRCC) wich displayed positive DaTSCAN signal in at least one of the lesions identified with CT
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End point type |
Primary
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End point timeframe |
From start to end of trial. 2017-07-14 to 2018-07-04
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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: The results of the trial were planned to be presented with descriptive statistics. However, the “early stopping rule” was applied and the study was stopped after analysis of five patients, where four patients had ccRCC and all five displayed negative DaTSCAN-signal. Thus, no statistical calculations could be performed on this material. |
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Attachments |
Primary endpoint DaTSCAN analysis Demography |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
proportion of Datscan positivity in non-clear cell RCC | |||||||||||||||
End point description |
To investigate whether DaTSCAN displays no positive signal in CT lesions in research subjects with tumors classified as non-clear cell renal cell carcinoma by pathologist. Negative signal was considered <3 times background signal in lesion identified by CT.
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End point type |
Secondary
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End point timeframe |
All patients was consequtively evaluated after completed examination. Timeframe is thus from first included patient 2017-07-14 to the last included patient 2018-07-04
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| Notes [2] - One out of five enrolled patients had non-ccRCC subtype according to pathological assessment |
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Infiltration of cancer cells in surgically removed DaTSCAN positive lymph nodes | ||||||||||||||||
End point description |
Does surgically removed DaTSCAN positive lymph nodes exhibit infiltration of clear cell renal cell carcinoma cells, regardless of the CT status? Measured as proportion of patients with DaTSCAN positive lymph nodes that contained tumor cells.
DaTSCAN signal was considered positive when >3 times higher signal intensity to background.
N.B. No lymph nodes displayed positive DaTSCAN-signal in any of the included patients, neither were any lymphnodes removed and analyzed for infiltrationg tumor cells in any of the patients.
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End point type |
Secondary
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End point timeframe |
Full trial from surgery of first inrolled subject to surgery of last enrolled subject.
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Attachments |
Characterization of lesions identified byCT |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Does DAT mRNA levels reflect DaTSCAN signal in surgically removed tumor material? | ||||||||
End point description |
DAT-mRNA expression in primary tumor correlate with DaTSCAN signal where the surgically removed tumor material with high DaTSCAN intensity also exhibit high mRNA levels of DAT?
Surgically removed material from patients whom had given consent according to ethical approvals: LU680-08 and LU289-07, would be analyzed for mRNA levels of DAT expressed as mRNA expression relative to b-actin.
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End point type |
Secondary
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End point timeframe |
From first operated patient 2017-08-03 to end of study 2018-09-12
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Attachments |
compiled endpoint results |
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| Notes [3] - No surgically removed material was accessible for analysis and no positive DATSCAN signal was seen |
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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 |
AE were reported consecutively for each patient while included in the trial at the following timepoints: datscan injection, spect analysis, followup phone call.
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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 |
10
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Reporting groups
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Reporting group title |
Study population
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Reporting group description |
This is a exploratory open single arm trial, including a small number of patients with suspected disseminated renal cell carcinoma. The objective of the trial is to investigate whether DaTSCAN with subsequent SPECT can be used for detection of clear cell renal cell carcinoma (ccRCC) tumors. Recruited patients with suspected disseminated kidney cancer will, after informed consent to participate in the study, be examined using CT and DaTSCAN followed by SPECT. DaTSCAN is injected intravenously and followed by SPECT examination 5h later. The images from the DaTSCAN investigation will be analyzed and anatomically compared to CT-scan from the same the patient. Any adverse effects during the study will be reported. | ||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||
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| 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: The were no events reported during this study. Incidents may be observed by a doctor / nurse or reported by the subjects themselves. The subjects were asked an open question "Have you had any health problems since taking potassium iodide?" at each relevant study visit (below). • When injecting DaTSCAN (Ioflupan I123) • Immediately after the SPECT investigation • 2 days after the DaTSCAN examination (through telephone interview from research nurse) |
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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. | |||
| Only 5 out of 10 intended patients were recruited in the study due to "early stopping rule": "End study if 4 patients with verified ccRCC all display negative DaTSCAN signal in all lesions. | |||
