Clinical Trial Results:
Can 89Zr-atezolizumab PET scan identify patients with metastatic invasive lobular breast cancer who will respond to chemotherapy-immune checkpoint inhibition?
Summary
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EudraCT number |
2019-001197-28 |
Trial protocol |
NL |
Global end of trial date |
01 May 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Oct 2022
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First version publication date |
12 Oct 2022
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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 |
201900180
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04222426 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
University Medical Centre Groningen
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Sponsor organisation address |
Hanzeplein 1, Groningen, Netherlands, 9713 GZ
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Public contact |
Department of Medical Oncology, University Medical Center Groningen, +31 503612821, c.p.schroder@umcg.nl
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Scientific contact |
Dr. C.P. Schröder, University Medical Center Groningen, +31 503612821, c.p.schroder@umcg.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 May 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 May 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
01 May 2022
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the feasibility to detect a change in tumor PD-L1 expression on a 89Zr-atezolizumab PET scan, before and after two carboplatin induction treatments.
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Protection of trial subjects |
89Zr-atezolizumab injection is safe, only one related low-grade adverse event (pruritus) has been noted in 1 out of 22 patients who completed the full imaging series of up to four 89Zr-atezolizumab PET scans. Whenever possible, to minimize the burden, intervention and patients’visits are preferably planned on the same day. If not possible, for this study, patients will make max. 3 extra visits to the hospital. Since 89Zr-atezolizumab is a radioactive compound, it will cause radiation burden to the patient.89Zr-atezolizumab PET implements a radiation burden of about 18 mSv for 37 MBq 89Zr-atezolizumab and 1.5 mSv for each low dose CT scan. For patients participating in the study, this implies a maximum additional radiation burden of 2 x (18 + 1.5) = 39 mSv. This additional radiation burden (moderate risk) is justifiable in this category of adult patients with metastatic cancer.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Dec 2019
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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: 1
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Worldwide total number of subjects |
1
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EEA total number of subjects |
1
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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) |
1
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Due to the COVID pandemic inclusions were possibly slow. Due to the closure of the main study (GELATO) only 1 patient has been included in the study. | ||||||
Pre-assignment
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Screening details |
Due to the closure of the main study (GELATO) only 1 patient has been included in the study. | ||||||
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 | ||||||
Blinding implementation details |
not applicable.
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Arms
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Arm title
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89Zr-atezolizumab PET scan | ||||||
Arm description |
All patients will undergo two 89Zr-atezolizumab PET scans, one at baseline and one after two doses carboplatin induction treatment. The 89Zr-atezolizumab PET scan will be performed 4 days after tracer injection. Procedures within the ImaGelato study will be completed after the two 89Zr-atezolizumab PET scans, but patients will continue treatment with carboplatin combined with atezolizumab in the GELATO trial. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
[89Zr]-Atezolizumab
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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 |
Total of 37 MBq megabecquerel(s)
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Baseline characteristics reporting groups
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Reporting group title |
89Zr-atezolizumab PET scan
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Reporting group description |
All patients will undergo two 89Zr-atezolizumab PET scans, one at baseline and one after two doses carboplatin induction treatment. The 89Zr-atezolizumab PET scan will be performed 4 days after tracer injection. Procedures within the ImaGelato study will be completed after the two 89Zr-atezolizumab PET scans, but patients will continue treatment with carboplatin combined with atezolizumab in the GELATO trial. | ||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
89Zr-atezolizumab PET scan
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Reporting group description |
All patients will undergo two 89Zr-atezolizumab PET scans, one at baseline and one after two doses carboplatin induction treatment. The 89Zr-atezolizumab PET scan will be performed 4 days after tracer injection. Procedures within the ImaGelato study will be completed after the two 89Zr-atezolizumab PET scans, but patients will continue treatment with carboplatin combined with atezolizumab in the GELATO trial. |
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End point title |
Change in tumor uptake between 89Zr-atezolizumab PET scan at baseline and after two carboplatin induction treatments, defined as decline or increase of standardized uptake value [1] | ||||||
End point description |
Change in tumor uptake between 89Zr-atezolizumab PET scan at baseline and after two carboplatin induction treatments, defined as decline or increase of standardized uptake value (SUV) of 30% or more, described as per lesion and per patient. For the two different time points we will calculate the SUV for all lesions and patients. Relative decrease or increase in SUV units between different time points will be calculated for all lesions and patients, and recorded as percentage of SUV decrease or increase.
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End point type |
Primary
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End point timeframe |
2 years
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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: descriptive statistics |
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No statistical analyses for this end point |
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End point title |
The relation between standardized uptake value (SUV) on 89Zr-atezolizumab PET scan, to response to carboplatin-atezolizumab | ||||||
End point description |
Relation of 89Zr-atezolizumab tumor uptake (at baseline, after carboplatin induction, and change between the two scans) per lesion and per patient with response to carboplatin-atezolizumab per lesion and per patient. For the 89Zr-atezolizumab PET scans, uptake will be quantified with SUV units for both time points.
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End point type |
Secondary
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End point timeframe |
2 years
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No statistical analyses for this end point |
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End point title |
The relation of 89Zr-atezolizumab tumor uptake at baseline and after two courses of carboplatin, with tumor biopsy assessments | ||||||
End point description |
Relation of 89Zr-atezolizumab tumor uptake at baseline and after carboplatin induction, with tumor biopsy assessments (for example PD-L1 immunohistochemistry (IHC)). We will investigate whether PD-L1 expression is associated with 89Zr-atezolizumab uptake. The relationship between tumor PD-L1 expression (measured in pre-treatment biopsy and induction treatment biopsy), and 89Zr-atezolizumab tumor uptake will be described.
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End point type |
Secondary
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End point timeframe |
2 years
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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 |
SAEs within 7 days of first knowledge for SAEs that result in death or are life threatening followed by a period of maximum of 8 days to complete initial report. All other SAEs within 15 days after sponsor has first knowledge.
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Assessment type |
Systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||
Dictionary version |
4
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Frequency threshold for reporting non-serious adverse events: 2% | |||
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: no adverse events observed |
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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. | |||
The main study, and thus this trial, has a slow inclusion known by criteria such as: no bone biopsies possible, measurable disease required, which certainly in this exceptional subpopulation of lobular breast cancer patients proved to be very severe |