Objectives: The immunogenic effects of adrenal SMART schemes may vary even though the local tumor control rates are high. Our objective is to study the dose-related immunological signals accompanying the delivery of SMART to adrenal metastases using…
ID
Source
Brief title
Condition
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters/endpoints: This hypothesis generating study aims to
characterize the immunological effects of different well-tolerated risk-adapted
SMART schedules. The primary study endpoints will be the immune responses in
the peripheral blood. The endpoints will be assessed by examination liquid
biopsies and FACS analysis on peripheral blood to detect immune modulation.
Secondary outcome
Secondary endpoints will be local tumor control rates and correlation of
measured immune parameters with PTV coverage and rates of tumor regression.
Background summary
Rationale: A meta-analysis revealed that the local control rates with SABR make
it a good alternative to surgery for adrenal metastases (Chen et al., IJROBP
2020). Ablative SABR doses were not uniformly used due to concerns about
toxicity. An explanation for the favorable outcomes with SABR may be a
radiation-induced immunological response against tumor cells, which can enhance
systemic immune responses. However, this so-called abscopal response appears to
be dose/schedule dependent. SMART was introduced at our center in 2016,
allowing for a safe delivery of high dose SABR. SMART is now the most
frequently used local modality for adrenal metastases at our center [van Vliet
C, ESTRO submission]. We propose an exploratory study of MR-guided SABR in
patients with adrenal metastases to evaluate: 1) the immune responses induced
by different SABR schemes used to treat adrenal metastases and 2) SABR schemes
that may be preferred for use in trials of oligometastastic disease. We believe
this information will provide a basis for future study designs in which the
immunological response resulting from a certain fractionation schedule of SABR
could be leveraged to improve outcome further, e.g. by combination therapy of
radiotherapy and immunotherapy.
Study objective
Objectives: The immunogenic effects of adrenal SMART schemes may vary even
though the local tumor control rates are high. Our objective is to study the
dose-related immunological signals accompanying the delivery of SMART to
adrenal metastases using standard SABR schedules. Specifically, we will explore
the pre- during- and post- SABR immune status in blood using FACS analyses,
NanoString PlexSet* analyses of IFN type-I related response genes in peripheral
blood mononuclear cells (PBMC) and Tumor Educated Platelet (TEP) analyses
Study design
Study design: Single-arm, non-randomized, exploratory trial evaluating
immunological and molecular effects of SABR for adrenal metastases
Study burden and risks
Burden and risks are limited, since we ask only for peripheral blood samples
3-4 times during this trial.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
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:
1. Have adrenal metastases, for which MR-guided SABR has been recommended
following dis-cussions within a multi-disciplinary tumor board.
2. Be willing and able to provide written informed consent for the trial.
3. Be 18 years of age on day of signing informed consent.
Exclusion criteria
1. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy
or any other form of immunosuppressive therapy within 30 days prior to the
MR-guided SABR.
2. Has had prior chemotherapy, targeted small molecule therapy, or radiotherapy
within 30 days prior to MR-guided SABR.
3. Has a known additional malignancy that is progressing or requires active
treatment. Exceptions include basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, or in situ cervical cancer that has undergone
potentially curative therapy.
4. Has an active autoimmune disease requiring systemic treatment within the
past 3 months or a syndrome that requires systemic steroids or
immunosuppressive agents. Subjects that require intermittent use of
bronchodilators or local steroid injections would not be excluded from the
study. Subjects with hypothyroidism stable on hormone replacement will not be
excluded from the study.
5. Has an active infection requiring systemic therapy.
6. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject*s participation for the full du-ration of the trial, or is not in the
best interest of the subject to participate, in the opinion of the treating
investigator.
7. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2
antibodies) or a known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C
(e.g., HCV RNA [qualitative] is detected).
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 | NL77647.029.21 |