The primary objective of this study is to optimize a workflow for identification of circulating melanoma cells in LA using flow cytometry. Secondary objectives include the detection of known mutations in different CMC subsets.
ID
Source
Brief title
Condition
- Skin neoplasms malignant and unspecified
- Skin neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study will be to determine the percentage of
patients with cells positive for any melanoma specific marker identified by
flow cytometric analysis of LA product.
Secondary outcome
Secondary endpoints are the comparison of putative CMC counts as identified by
flow cytometry and CellSearch in blood and LA product and mutation status of a
mutation, present on primary- or metastatic tumor tissue, in different CMC
subsets as identified by flow cytometry.
Background summary
Recent developments on the treatment of metastatic melanoma have changed
perspectives of patients with a previously poor prognosis. Promising results of
immuno- and targeted therapy in the metastatic setting has shifted current
focus to the application of those treatments in the adjuvant setting. However,
treatment with these modalities yields significant toxicity leading to
hospitalization and treatment withdrawal 15% of the patients. Furthermore, in
studies conducted in the adjuvant setting, the number needed to treat was
rather high, indicating a significant proportion of the patients do not benefit
from adjuvant systemic treatment. This emphasizes the need for the
identification of a prognostic biomarker enabling to discriminate patients who
would benefit from adjuvant therapy. In other cancer types, circulating tumor
cells (CTCs) are of significant prognostic value. However, regular methods to
identify CTCs are not suitable for identification of melanoma cells since those
methods are based on Epithelial Cell Adhesion Molecule (EpCAM) isolation
techniques. Moreover, literature has reported melanoma cells to be
phenotypically heterogenic, complicating capture methods based on one or two
antibodies. Therefore, we plan to identify circulating melanoma cells (CMCs)
using multicolor flow cytometry targeting different melanoma specific antigens.
Given the expected low numbers of CMCs in the adjuvant setting, we aim to
identify CMCs in leukapheresis (LA) material, enabling detection of CMCs in
larger volumes of blood. Furthermore, we aim to confirm true CMC identity of
cells designated as CMCs by flow cytometry by downstream identification of a
known mutation.
Study objective
The primary objective of this study is to optimize a workflow for
identification of circulating melanoma cells in LA using flow cytometry.
Secondary objectives include the detection of known mutations in different CMC
subsets.
Study design
Prospective, observational study
Study burden and risks
All patients are asked to undergo a single LA procedure which will take a
maximum of 2 hours. A maximum volume of calculated total body volume, which is
approximately 5 L peripheral blood will be processed with the use of an Optia
Spectra Cell Separator. Patients do not benefit from this study. The most
common adverse events to be expected are pain or bruising at the venipuncture
site (1-5%), apprehension or fainting associated with venipuncture (1-5%),
fluid imbalance (0.01-0.1%) and citrate anticoagulant infusion-related symptoms
resulting in tingling or buzzing around the mouth or fingers (20-50%). All
patients will receive intravenous calcium to prevent this. The risk of adverse
events associated with LA is considered negligible.
Dr Molewaterplein 40 40
Rotterdam 3015 GD
NL
Dr Molewaterplein 40 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
* Patients with metastatic melanoma
* Starting new line of systemic treatment for metastatic disease, irrespective
of treatment modality (i.e. BRAF-targeted therapy or immunotherapy) or with
progression under current treatment
* Age *18 years
Exclusion criteria
* Known hypersensitivity to the anticoagulant used for apheresis
* Inadequate cardiac function or severe cardiovascular comorbidity
a. Heart failure NYHA class III/IV
* Hemoglobin level < 6.0 mmol/L
NOTE: red blood cell transfusions are allowed to increase the hemoglobin level
at the discretion of the investigator
* Coagulation disorders as defined by one of the following:
NOTE: the use of all types of anticoagulant therapy is permitted
a. Coagulation disorder in medical history
b. Platelet count < 40 x 109/L;
Patients not on anticoagulant therapy which affects PT or APTT if:
c. PT > 1.5 x ULN or PT-INR > 1.5 x ULN
d. APTT > 1.5 x ULN
Patients who take anticoagulant therapy which affects PT or APTT if:
e. PT or APTT > 1.5 x the upper limit of the desired therapeutic window
f. Total bilirubin > 2.5 x ULN
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 | NL67262.078.18 |