- part A: to identify the pharmacokinetic model that represents the [18F]FES kinetics most optimally and to validate simplified quantitative parameters of [18F]FES uptake. - part B: to investigate the repeatability of simplified quantitative…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- part A: the most optimal pharmacokinetic model (for instance the single
tissue reversible, two tissue reversible or irreversible model) will be
identified.
Depending on the model, the most robust and stable parameter for
quantification of tracer uptake in tumor lesions (for instance the net influx
rate (Ki)
or volume of distribution (VT)) will be correlated with standardized uptake
values (SUVs) and tumor-to-blood ratios (TBRs).
- part B: repeatability of simplified measures of [18F]FES uptake, i.e. SUVs
and TBRs, will be assessed.
Secondary outcome
Not applicable.
Background summary
16a-18F-fluoro-17b-estradiol ([18F]FES) is radioactive labeled estradiol,
developed for in vivo visualization of the estrogen receptor (ER) using
positron emission tomography (PET). To date, [18F]FES PET has been mainly
explored as a diagnostic imaging tool to assess ER expression, thereby
identifying locations of disease and their potential sensitivity to endocrine
therapy, respectively. The primary aim of this project is to extend the
application of [18F]FES PET as a baseline diagnostic imaging biomarker for ER
expression to use it as an (early) treatment response marker. However, for such
an application, visual assessment alone may not be sufficient and a more
rigorous quantitative image analysis is needed. Therefore, in this project we
shall first derive the optimal pharmacokinetic model for full quantitative
analysis of [18F]FES uptake and, subsequently, we shall assess the validity of
simplified, clinically feasible, quantitative parameters of [18F]FES uptake in
5 patients with metastatic estrogen receptor positive (ER+) breast cancer (part
A). In addition, the repeatability of these simplified parameters will then be
investigated in another 10 patients (part B).
Study objective
- part A: to identify the pharmacokinetic model that represents the [18F]FES
kinetics most optimally and to validate simplified quantitative parameters
of [18F]FES uptake.
- part B: to investigate the repeatability of simplified quantitative
parameters of [18F]FES uptake.
Study design
- part A: each patient will receive 2 venous cannulas, one for tracer
administration and the other for venous blood sampling. Prior to infusion,
blood will
be drawn to determine creatinine levels (only if not performed during routine
care), plasma estradiol levels and sex hormone binding globuline
(SHBG). Next, a low-dose CT scan of the thorax will be performed for
attenuation correction of PET and anatomical correlation, followed by a 90-min
dynamic [18F]FES PET scan of the thorax which will start directly after
intravenous administration of 200 MBq (±10%) [18F]FES. During the dynamic
scan, 9 venous blood samples will be drawn to measure parent fraction of
[18F]FES and metabolites.
- part B: all patients will undergo whole body static [18F]FES PET/CT imaging
twice <=1 week. For this, each patient will receive 1 venous cannula
which will first be used for blood sampling (for determining creatinine
levels - only if not performed during standard of care and plasma estradiol and
SHBG levels) and then for tracer administration. Next, a whole body low-dose
CT scan (head to mid-thigh) will be performed for attenuation
correction of PET and anatomical correlation, followed by a whole body
[18F]FES PET scan after intravenous administration of 200 MBq (±10%)
[18F]FES. The precise timing for performing the PET scan after tracer
administration will be determined during part A.
Study burden and risks
Each patient in part A and B will receive intravenous cannula(s) for tracer
injection and blood sampling, causing potentially transient discomfort at the
site of the cannula insertion. For the PET scans, patient will be asked to fast
for 4 hours. Radiation exposure from a [18F]FES PET scan usually ranges between
4.0-5.0 mSv. In part A, the [18F]FES PET scan will be accompanied by a low-dose
CT of the thorax exposing patients to an additional 0.5 mSv whereas in part B a
whole body low-dose CT scan will be performed exposing patients to 3.0 mSv. The
total radiation burden for part A and B is 4.5-5.5 and 7.0-8.0 mSv x 2 (as in
part B patients will receive the scan twice), respectively. This radiation
burden is considered justifiable when compared to the information that can be
obtained from this study, in this patient group with breast cancer. This study
will help to extend the application of [18F]FES PET from a baseline diagnostic
imaging biomarker for ER expression to an (early) treatment response marker,
thus potentially preventing patients from toxic or futile treatments.
De Boelelaan 1118
Amsterdam 1081 HV
NL
De Boelelaan 1118
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
- Histologically proven metastatic ER+ (>10% positive stained cells
usingimmunohistochemistry) breast cancer on the latest biopsy
- Postmenopausal females aged 18 years or older at screening. Postmenopausal
status is defined as one of the following:
a. age >=60 years
b. age <60 years and amenorrhea for >12 months in the
absence of interfering
hormonal therapies (such as LH-RH agonists and
ER-antagonists)
c. patient age <60 years using LH-RH agonists should
continue LH-RH-agonists
until after the PET procedures
d. previous bilateral oophorectomy or medically confirmed
ovarian failure
- [18F]FDG PET, CT and/or a bone scan should be performed as part of routine
clinical staging (<=4 weeks prior to screening)
- Patients should have metastases in the scanning field of view, all located
outside of the liver
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
- Estimated glomerular filtration rate (eGFR) >=30 ml/min
- Written and signed informed consent
Exclusion criteria
- History with another cancer within the last 5 years, except cancer treated
with curative intent and no evidence of disease as judged by the treating
physician.
- Use of selective estrogen receptor modulators (SERMs) or downregulators
(SERDs) for current breast cancer such as Tamoxifen/Fulvestrant (<=5
weeks prior to screening) or investigational drug therapy
- Pregnancy or lactating women
- Any medical, psychological or social condition that may interfere with the
subject*s safety and participation in the study, will lead to exclusion from
this study
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-000610-42-NL |
| CCMO | NL76658.029.21 |