• To perform full kinetic modeling of [18F]F-AraG for the uptake in tumor lesions and healthy organs (e.g. spleen) by exploring different kinetic models and outcome measures as well as its test-retest (TRT) variability to guide the selection of an…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
- Congenital respiratory tract disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Dynamic tumor tracer uptake parameters will be summarized to perform tracer
kinetic modeling using standard nonlinear regression techniques to fit the
dynamic [18F]F-AraG tumor time activity curves (TACs) to different (i.e.,
1-tissue, irreversible 2-tissue, and reversible 2-tissue) compartment models
using the measured metabolite corrected plasma time-activity curve as input
function. The optimal model will be selected based on the goodness of fit. The
most appropriate parameter will be chosen depending on the optimal model and
its test-retest variability. Dynamic uptake parameters of interest will be
correlated with simplified static uptake parameters derived from the whole-body
scans. Correlations will be made between hotspots and cold-spots as seen on the
[18F]F-AraG PET and the corresponding spots on the resection specimen for
automated quantification of CD8+ cells using VECTRA and tumor inflammation
signature using gene expression analyses.
Secondary outcome
-
Background summary
The efficacy of immunotherapy and patient selection for combinatorial
immunotherapy strategies would greatly improve if the tumor microenvironment
(TME) could be characterized more accurately. Positron emission tomography
(PET) using tracers that target immune cell subsets may provide a non-invasive
means to immune profile the TME. Imaging T-cells can help in identifying *hot*
tumors, or parts of the tumor mass that have high concentrations of tumor
infiltrating T-cells and also provide information on its activation.
A promising tracer to image activated T-cells is [18F]F-AraG. We hypothesized
that [18F]F-AraG will accumulate in activated T-cells. Therefore, we expect
that [18F]F-AraG and PET will enable to (reproducibly) identify tumors and
tumor areas with high concentrations of tumor infiltrating activated T-cells on
pathological assessment.
Study objective
• To perform full kinetic modeling of [18F]F-AraG for the uptake in tumor
lesions and healthy organs (e.g. spleen) by exploring different kinetic models
and outcome measures as well as its test-retest (TRT) variability to guide the
selection of an optimal PET pharmacokinetic model
• To correlate the relationship between the tumor uptake of [18F]F-AraG and the
number of CD8 T-cells amongst others as measured by Immunohistochemistry (IHC)
and gene expression
Study design
Open-label, non-controlled, non-randomized single center, single arm, imaging
trial
Intervention
All patients will undergo [18F]F-AraG PET scanning according to the
institutional pharmacokinetic tracer modeling protocols
Study burden and risks
Prior to the injection of the tracer, venous blood will be drawn for
immunological assessment of T-cell subsets. All patients will undergo 2 extra
scanning procedures (test and re-test on consecutive days). Per scanning
procedure, patients will be lying for approximately 90 minutes on the scanner
and will receive a total radiation burden of approximately 12 mSv for both
procedures. In the first 5 patients (part-1), a cannula will be inserted in an
arm vein and in the radial artery (only test, not re-test) to draw blood (7cc),
manually at 7 time points. In part-1, no more than 147+30cc (for test+retest,
respectively) blood will be drawn per patient. In the other 5 patients
(part-2), all procedures will be the same except for the arterial cannula,
which will not be inserted, so, no arterial blood will be drawn, meaning that
no more than 98+30cc of blood will be drawn per patient in part-2. Patients
will derive no direct benefit from participating in this trial. The insights
obtained in the translational part of this study can be of high interest and
benefit assessment of T cell activation state and its treatment related changes
in future cohorts of NSCLC patients.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
1. Histologically confirmed NSCLC, a histological biopsy is mandatory.
2. Patients that are resectable upfront as per multidisciplinary tumor board
evaluation.
3. Be willing and able to provide written informed consent for the trial.
4. Be above 18 years of age on day of signing informed consent.
5. Have a performance status of 0-1 on the ECOG Performance Scale at screening.
Exclusion criteria
1. Subjects with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalent) or other
immunosuppressive medications within 14 days of screening. Inhaled or topical
steroids, and adrenal replacement steroid >10 mg daily prednisone
equivalent, are permitted in the absence of active autoimmune disease.
2. Psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
3. Patient is pregnant or breastfeeding or expecting to conceive within the
projected duration of the trial, starting with the screening visit through 12
weeks after the last [18F]F-AraG PET scan.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-001489-40-NL |
| CCMO | NL77310.029.21 |