New Strategies to Detect Cancers in Carriers of Mutations in RB1

Summary

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.

Conditions

• Retinoblastoma
• Secondary Primary Malignancies After Retinoblastoma

Interventions

OTHER

blood draw

Control samples for the Rb survivor group (adult) are already available at the VUMC for the platelet study; unselected volunteers from an anti-cancer campaign. Control samples (adult) for the EV study will be collected in a blooddrive at the Essen site. Pediatric patients. For the pediatric Rb patients, blood draw is part of standard care (3mth-4y). The control blood samples of healthy children (12) will be drawn from healthy children, where the blood draw is already part of otherwise planned care (e.g. patients which are completely healthy besides having an unrelated problem for which surgery is required). Controls will be age-matched as much as possible.

Sponsors & Collaborators

• University Hospital, Essen

  collaborator OTHER

• Institut Curie

  collaborator OTHER

• Ligue contre le cancer, France

  collaborator OTHER

• Amsterdam UMC, location VUmc

  lead OTHER

Principal Investigators

• Armida Fabius · VUMC

Eligibility

Min Age

0 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-12-13

Primary Completion

2023-03-31

Completion

2023-03-31

Countries

• France
• Germany
• Netherlands

Study Locations