A) To quantify the difference in 18F-FDG uptake (expressed as SUVmax, SUVmean and SUVpeak) in tumor lesions within 7 days before and between 7 and 14 days after treatment initiation with immune checkpoint inhibitors with or without chemotherapy. B)…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
For each tumor, a volume of interest (VOI) will be drawn on the PET scan images
and standard uptake values (SUVmax, SUVmean, SUVpeak), metabolically active
tumor volume (MATV) and total lesion glycolysis (TLG) will be measured and the
change in parameter values calculated and related to treatment outcome in terms
of PFS and OS; response evaluation criteria in solid tumors). Change in the
percentage, activation status and ratio of selected immune cells in PBMC's and
if avaible in TDLNs will be calculated and related to the PET results and
outcome in terms PFS and OS.
Secondary outcome
N.A.
Background summary
To identify patients that will benefit from treatment with mAbs like nivolumab
or pembrolizumab, it is important to find a predictive biomarker. In this study
we will explore potential biomarkers, 18F-FDG uptake assessed by FDG-PET and
immunophenotyping of peripheral blood mononuclear cells (PBMC) and if avaible
tumor-draining lymph nodes (TDLNs).
In the research setting, PET is increasingly being used to study early changes
of biologic effects during and after cancer therapy. Migration and activation
of immune cells lead to an increase of FDG uptake. In the early phase of immune
therapy, we expect an influx of inflammatory cells in the tumor to cause a
higher metabolic activity in patients who respond to immune checkpoint
inhibitors.
Change in subsets of immunce cells in peripheral blood cells after nivolumab
treatment is known. We will explorate these changes further and correlate them
with respons to nivolumab.
Recently we showed in a pilot study that fine needle aspiration (FNA) combined
with multi parameter flow cytometry (FACS) immunophenotyping is a feasible,
rapid and sensitive method to detect lymphoid marker expression that is unique
to TDLNs and different from blood and non-tumor draining lymph nodes (NTDLNs)
(manuscript in preparation). We hypothesize that an early read-out of TDLN
immunophenotyping predicts the efficacy of immune checkpoint inhibitors.
Study objective
A) To quantify the difference in 18F-FDG uptake (expressed as SUVmax, SUVmean
and SUVpeak) in tumor lesions within 7 days before and between 7 and 14 days
after treatment initiation with immune checkpoint inhibitors with or without
chemotherapy.
B) To analyse immune cell subsets in PBMC and TDLNs and compare changes before
and one week after treatment initiation.
Study design
A pilot study with biomarker exploration
Study burden and risks
The burden and risks associated with participation are considered low. The
study procedures are part of the routine diagnostic workup of NSCLC patients
and thus common practice for pulmonologists on a weekly basis. Use of positron
emitting radionuclides means exposure to ionizing radiation. The radiation
exposure will be 9 mSv in total per patient (4.5 mSv per PET scan). One PET
scan is part of routine care and the other is solely for the purpose of this
study. The long term risk of developing a secondary malignancy due to radiation
exposure is theoretical, because of the limited life expectancy of patients
with stage IV NSCLC. Patients do not derive benefit from the PET scan results.
Patients who will be approached for study participation already have an
indication for a pretreatment PET-CT and EBUS procedure. The early on-treatment
endoscopy (not mandatory) and PET scan are however not part of regular care and
are performed for the purpose of this study. Since there is a lack of a well
performing predictive biomarker of response, the results of this imaging
biomarker study can be of high interest for NSCLC patients that are eligible
for treatment with checkpoint inhibitors in the future. Blood withdrawal is
considered as a safe procedure.
Plesmanlaan 121
Amsterdam 1066CX
NL
Plesmanlaan 121
Amsterdam 1066CX
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
* willing and able to provide written informed consent for the study.
* * 18 years of age on day of signing informed consent.
* confirmed diagnosis of NSCLC.
* Histological tumor biopsy for PD-L1 IHC assessment (DAKO assay) available.
* Eligible for first line chemo-immunotherapy or 2nd line and beyond PD-(L)1
immunotherapy monotherapy.
* Measurable disease according to RECIST v1.1.
* WHO performance status of 0*2.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
* Has had prior chemotherapy, targeted small molecule therapy, or radiation
therapy within 2 weeks prior to the baseline PET-scan.
* Has an active infection or had an active infection within 2 weeks prior to
baseline PET-scan.
* Has a known history of hypersensitivity to contrast material.
Design
Recruitment
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 |
|---|---|
| CCMO | NL62294.031.17 |