- The development of blood-based tests, either platelet or EV-based, for the detection of (the type of) tumors in RB1-mutation carriers.- Determine the non-cancerous baseline in adult RB1-mutation carriers (heritable-Rb-survivors).- Contribute to…
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
- Ocular neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- The development of a test which can detect cancers in the RB1-mutation
carriers.
Secondary outcome
- The determination whether either the EV or the platelet-based technique
performs superior as a test, or that both test will be complementary.
- The cell free DNA fraction will also be isolated from collected blood
samples. This material will serve as part of an contingency plan when EV or
platelet testing is not discriminative enough. Furthermore, if additional
funding is acquired by the Curie site, cfDNA from patients with SPMs (10
patients are expected with SPMs) will be used for additional testing. Results
will be compared to germline DNA isolated from leukocytes present in the buffy
coat and to second tumor material if available. The samples will be whole exome
sequenced, combined with targeted sequencing of specific regions. For this
study, involving whole genome sequencing, an extra consent form will be signed
by the patients.
Background summary
Individuals with a cancer predisposition due to a mutation in the paradigm
tumor suppressor gene RB1, have a high risk to develop the childhood cancer
retinoblastoma (Rb). Biopsies are not possible in Rb, before treatment
selection. Heritable Rb patients have also a high risk to develop other types
of second primary, either childhood or adult, malignancies (SPMs), notably
sarcomas and melanomas. Remarkably, SPMs are now the leading cause of death in
heritable-Rb-survivors. Unfortunately, there are no well-developed regular
surveillance protocols for SPMs in Rb survivors available right now. Recently,
new non-invasive cancer test have been developed, based on either
RNA-sequencing data from platelets (ThromboSeq), on extracellular membrane
vesicles (EVs) on cell free DNA (cfDNA) or on other blood fractions derived
from tumor cells present in blood.
Study objective
- The development of blood-based tests, either platelet or EV-based, for the
detection of (the type of) tumors in RB1-mutation carriers.
- Determine the non-cancerous baseline in adult RB1-mutation carriers
(heritable-Rb-survivors).
- Contribute to the biobanking of blood and cancerous tissues from RB1-mutation
carriers with SPMs.
Study design
Cross-sectional multicenter trial.
Study burden and risks
Two blood samples totalling 10ml blood will be collected for every participant.
Additionally, a short questionnaire has to be filled in concerning their and
their family*s cancer history. In addition questions will be asked about the
presence of infectious diseases in the week before blood draws. Blood draws
will be done, when participants are already present in the hospital for other
appointments, and thus no extra visits are required. For all children, blood
will be collected through an already present IV, and so no extra venepuncture
is required. Children have to be included because Rb is a tumor only present in
this patient group.
De Boelelaan 1118
Amsterdam 1081 HZ
NL
De Boelelaan 1118
Amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
- Adult:
Group 1: germline mutation RB1
Group 2 (control): no germline mutation RB1
- Pediatric:
Group 1: mutation RB1 and retinoblastoma
Group 2 (control): no mutation RB1
Exclusion criteria
- Adult:
Group 1: concomitant heritable (inherited) disorder other than caused by
monoallelic mutation of RB1
Group 2 (control): cancer or already known cancer predisposition syndrome
- Pediatric:
Group 1: concomitant heritable (inherited) disorder other than caused by
monoallelic mutation of RB1
Group 2: cancer or already known cancer predisposition syndrome
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 | NL64672.029.18 |