NCT04164134: NIRBTEST

New Strategies to Detect Cancers in Carriers of Mutations in RB1

Completed Last updated 25 July 2023

What this trial tests

trial testing blood draw in Retinoblastoma in 378 participants. Completed in 31 March 2023.

Timeline

13 December 2018

Primary endpoint
31 March 2023

31 March 2023

Quick facts

Lead sponsor	Amsterdam UMC, location VUmc
Status	Completed
Study type	OBSERVATIONAL
Enrollment	378
Start date	13 December 2018
Primary completion	31 March 2023
Estimated completion	31 March 2023
Sites	3 locations across France, Netherlands, Germany

Drugs / interventions tested

• blood draw — full drug profile →

Conditions studied

• Retinoblastoma — all drugs for Retinoblastoma →
• Secondary Primary Malignancies After Retinoblastoma — all drugs for Secondary Primary Malignancies After Retinoblastoma →

Sponsor

Amsterdam UMC, location VUmc — full company profile →

Who can join

Adults 0 to 99, any sex, with Retinoblastoma or Secondary Primary Malignancies After Retinoblastoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Rationale: 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), or on extracellular membrane vesicles (EVs) derived from tumor cells present in blood.

Objective:

* 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.
* The development of blood-based tests, either platelet or EV-based, for the detection of (the type of) tumors in RB1-mutation carriers.

Study design: Cross-sectional multicenter trial.

Study population:

* 40 Rb patients (children),
* 40 controls (children),
* 153 Rb survivors (adults),
* 153 controls (adults),
* 10 Rb survivors with SPM (children/adults).

Main study parameters/endpoints:

* 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.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

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. 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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Emerging Role of Extracellular Vesicles and Cellular Communication in Metastasis.
   Forder A, Hsing CY, Trejo Vazquez J, Garnis C. · · 2021 · cited 38× · PMID 34943937 · DOI 10.3390/cells10123429
2. Extracellular Vesicles for Clinical Diagnostics: From Bulk Measurements to Single-Vesicle Analysis.
   Tran HL, Zheng W, Issadore DA, Im H, et al · · 2025 · cited 25× · PMID 40720603 · DOI 10.1021/acsnano.5c00706
3. The detection, biological function, and liquid biopsy application of extracellular vesicle-associated DNA.
   Guo S, Wang X, Shan D, Xiao Y, et al · · 2024 · cited 11× · PMID 39402599 · DOI 10.1186/s40364-024-00661-2
4. Extracellular vesicles in age-related diseases: disease pathogenesis, intervention, and biomarker.
   Putri PHL, Alamudi SH, Dong X, Fu Y. · · 2025 · cited 10× · PMID 40437603 · DOI 10.1186/s13287-025-04374-7
5. Extracellular vesicles and cancer stem cells: a deadly duo in tumor progression.
   Tayanloo-Beik A, Eslami A, Sarvari M, Jalaeikhoo H, et al · · 2024 · cited 6× · PMID 39091989 · DOI 10.3389/or.2024.1411736
6. Current trends in theranostic applications of extracellular vesicles in cancer.
   Almasry Y, Mustafa F, Alfuwais M, AlNachef S, et al · · 2025 · cited 3× · PMID 40530018 · DOI 10.3389/fonc.2025.1592006
7. Diagnostic and Therapeutic Utility of Extracellular Vesicles in Ocular Disease.
   Khristov V, Weber SR, Caton-Darby M, Campbell G, et al · · 2025 · cited 2× · PMID 39859553 · DOI 10.3390/ijms26020836
8. Potential Effect of Extracellular Vesicles in Clinical Settings of Lymphoma.
   Mamgain G, Yadav SRM. · · 2025 · PMID 39835236 · DOI 10.1007/s12291-023-01156-x