Primary objectives:• To evaluate safety of repeat doses of [18F]AlF-RESCA-IL2.• To evaluate tumour uptake of [18F]AlF-RESCA-IL2 in patients with cancer.• To evaluate whole body distribution of [18F]AlF-RESCA-IL2 in cancer patients.Secondary…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Safety evaluation through summaries of adverse events per NCI CTCAE v5.0
criteria, changes in laboratory test results and changes in vital signs after
exposure to [18F]AlF-RESCA-IL2
• Evaluation of tumour [18F]AlF-RESCA-IL2 uptake by measuring standardised
uptake values in tumour lesions.
• Evaluation of [18F]AlF-RESCA-IL2 biodistribution in cancer patients on the
PET images by measuring standardised uptake values in healthy tissues and
organs.
Secondary outcome
• Correlation of [18F]AlF-RESCA-IL2 uptake in tumours, with T cell infiltration
in tumour biopsy samples, as determined by IHC.
• Correlation of [18F]AlF-RESCA-IL2 PET measurements with radiologic response
to treatment, according to (i)RECIST v1.1 criteria.
• Assessment of changes in tumour and normal organ tracer uptake after 2 weeks
of treatment, expressed as standardised uptake values.
Background summary
The rapidly evolving fields of tumour immunology and cancer immunotherapy have
resulted in several Food and Drug Administration (FDA) and European Medicines
Agency (EMA) approved immune checkpoint inhibitors (ICI) for different tumour
types. However, not all patients respond to these drugs. Moreover,
immunotherapeutic drugs require careful management of potential side effects.
Therefore, it would be of major interest to be able to know whether a specific
treatment induces an immune response.
The dynamic tumour microenvironment and tumour heterogeneity have raised
significant interest in objectifying the status of the microenvironment. Still,
the ability to monitor changes in the immune status of metastatic cancers is
limited. Current methods to monitor lymphocytes from whole blood or biopsies
from heterogeneous tumours do not necessarily reflect the dynamic and spatial
information required to monitor immune responses to therapeutic intervention.
Moreover, these responses may elicit whole body changes in immune cell numbers
and localization. Molecular imaging can noninvasively monitor whole-body
systemic and intratumoral alterations. Assessing abundance and localization of
immune cells before and during therapy would increase the understanding of the
dynamics of immunotherapeutic mechanisms, with the potential to provide
translatable methods for predicting and/or assessing responses.
IL-2 is a 15 kDa cytokine that plays an important role in the cellular immune
response. Its primary function involves stimulation of growth, proliferation,
activation, and differentiation of T cells. IL-2 induces its effects by binding
to transmembrane IL-2 receptors (IL-2Rs). The high-affinity IL-2R, consisting
of all three subunits (CD25, CD122, and CD132), is primarily present on
activated effector T cells and regulatory T cells (Treg). Whereas the
low-affinity IL-2R, consisting of two subunits (CD122 and CD132), is generally
found on naïve T cells and natural killer cells.
The migration of activated T cells was visualized using [18F]FB-IL2-PET in
mouse xenograft models. Furthermore, a clinical PET study using the tracer
[18F]FB-IL2 was performed in patients with metastatic melanoma before and
during immune checkpoint inhibitor therapy. Also, single-photon emission
computed tomography (SPECT) imaging of the IL-2R has previously been performed
in three patients with metastatic melanoma. However, PET-imaging provides
better spatial resolution and allows for more accurate quantification of tracer
uptake in tumour lesions and other tissues.
[18F]AlF-RESCA-IL2 is an improved version of the PET tracer [18F]FB-IL2, with
better imaging characteristics. The aim of this pilot study is to evaluate the
safety and imaging performance of [18F]AlF-RESCA-IL2.
Study objective
Primary objectives:
• To evaluate safety of repeat doses of [18F]AlF-RESCA-IL2.
• To evaluate tumour uptake of [18F]AlF-RESCA-IL2 in patients with cancer.
• To evaluate whole body distribution of [18F]AlF-RESCA-IL2 in cancer patients.
Secondary objectives:
• To assess changes in tumour and normal organ uptake after 2 weeks of ICI
therapy.
• To determine whether changes in visual and semi-quantitative
[18F]AlF-RESCA-IL2 PET measurements correlate with RECIST v1.1. radiology
responses.
• To correlate tumour tracer uptake with tumour immune cell infiltration as
assessed by immunohistochemistry (IHC).
Study design
An investigator-initiated, open-label clinical trial designed to evaluate the
safety and in vivo biodistribution of the PET tracer [18F]AlF-RESCA-IL2.
Intervention
Patients will be enrolled to undergo [18F]AlF-RESCA-IL2 PET imaging twice; the
first [18F]AlF-RESCA-IL2 PET scan will be performed at baseline, before
starting therapy. The second [18F]AlF-RESCA-IL2 PET scan will be performed
after 2 weeks of treatment, to minimize morphological changes in tumours
responding to the therapy.
Study burden and risks
For this study, patients have to make a maximum of 4 extra visits to the clinic
for screening, to have 2 PET-scan visits, and one biopsy taken before starting
treatment. In practice, most procedures will be combined with visits to the
hospital in the context of clinical care to minimse the burden.
[18F]AlF-RESCA-IL2 is a radioactive compound and therefore, will cause
radiation burden to the patient. The effective dose equivalent of [18F] tracers
was estimated to be roughly 0.02 mSv/MBq (8). For a diagnostic dose of
[18F]AlF-RESCA-IL2 equal to 200 MBq, the absorbed radiation dose will be around
4 mSv. Each PET scan will be made with a low dose attenuation correction CT
scan, which has an effective dose of 1.5 mSv. The radiation exposure will be
approximately (2x4) + (2x1.5) = 11 mSv.
Besides PET imaging, patients will be asked to provide a total of 5 blood
samples (38 mL).
A tumour lesion will be biopsied. Based on a literature review, the risk of
tumour biopsies is considered low, with a small risk of significant or major
complications or death. To keep this risk as low as possible only patients that
have safely accessible tumour lesions will be included in the study.
The risk associated with [18F]AlF-RESCA-IL2 is considered very low based on
preclinical testing. The tracer will be intravenously injected as a single dose
that will not exceed 50 microgram of protein, which is substantially lower than
the dose of interleukin-2 (Proleukin) that is clinically applied. Although
patients do not directly benefit from this study, results from this study will
be valuable for our understanding of the tumour immune response and will guide
further prospective research and hopefully treatment decisions.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
1. Age >= 18 years at the time of signing informed consent.
2. Patients with histologically confirmed diagnosis of locally advanced or
metastatic solid cancer, eligible for ICI therapy as part of routine care.
3. At least 1 lesion that is accessible per investigator*s assessment and
eligible for biopsy according to standard clinical care procedures.
4. Measurable disease, as defined by standard RECIST v1.1. Previously
irradiated lesions should not be counted as target lesions except for lesions
that have progressed after radiotherapy.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Life expectancy >= 12 weeks.
7. Signed informed consent.
8. Willingness and ability to comply with all protocol required procedures.
9. For female patients of childbearing potential and male patients with
partners of childbearing potential, agreement (by patient and/or partner) to
use a highly effective form(s) of contraception (i.e., one that results in a
low failure rate (< 1% per year) when used consistently and correctly)).
Exclusion criteria
1. Treatment with any other investigational agent or participation in another
clinical trial with therapeutic intent within 28 days prior to
[18F]AlF-RESCA-IL2 injection.
2. Evidence of an active infection that requires systemic antibiotics within 2
weeks prior to [18F]AlF-RESCA-IL2 injection.
3. Active HIV, Hepatitis-B or Hepatitis-C infection.
4. Any other diseases, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or
condition that contraindicates the use of [18F]AlF-RESCA-IL2, or that may
affect the interpretation of the results or render the patient at high risk
from complications.
5. Altered mental status, or any psychiatric condition that would prohibit the
understanding or rendering of informed consent.
6. Sponsor employee/member of the clinical site study team and/or his or her
immediate family
7. Pregnant or lactating females.
8. Concurrent use of systemic corticosteroids > 10 mg daily prednisone
equivalent.
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 | EUCTR2022-000040-30-NL |
| ClinicalTrials.gov | NCT05471271 |
| CCMO | NL81955.042.22 |