NCT04164134

Brief 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
378

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Dec 2018

Longer than P75 for all trials

Geographic Reach
3 countries

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 13, 2018

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

November 7, 2019

Completed
8 days until next milestone

First Posted

Study publicly available on registry

November 15, 2019

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2023

Completed
Last Updated

July 25, 2023

Status Verified

July 1, 2023

Enrollment Period

4.3 years

First QC Date

November 7, 2019

Last Update Submit

July 24, 2023

Conditions

RetinoblastomaSecondary Primary Malignancies After Retinoblastoma

Keywords

Retinoblastomablood testliquid biopsyRB1cancerSecondary primary malignanciesSPM

Outcome Measures

Primary Outcomes (1)

  • RNA expression on platelets and allelic DNA balance of EVs in the blood of adult RB1 mutation carriers (Rb-survivors) and retinoblastoma patients (children).

    blood analyses at time of inclusion to determine baseline

    blood will be taken at study inclusion, patients will be followed throughout the study, max 3 years and 9 months.

Secondary Outcomes (1)

  • RNA expression on platelets, allelic DNA balance of EVs in blood and genomic analysis on tumor tissue of RB1-mutation carriers diagnosed with a second primary malignancy.

    blood will be taken at study inclusion, patients will be followed throughout the study, max 3 years and 9 months. In case of second primary tumor a second sample will be taken.

Study Arms (5)

Retinoblastoma patients (children)

Children that are currently diagnosed with a retinoblastoma. Blood will be collected and a short questionnaire has to be filled by the parent or legal guardian. Samples will be taken together with standard care blood draw, so no extra venepuncture is required.

Other: blood draw

Controls (children)

Children with an unrelated problem/condition for which surgery is needed Blood will be collected and a short questionnaire has to be filled by the parent or legal guardian. Samples will be taken during standard care blood draw, so no extra venepuncture is required.

Other: blood draw

Retinoblastoma survivors (adults)

Adults that carry a RB1 germline mutation and were diagnosed and treated for retinoblastoma in the past. Blood will be collected and a short questionnaire has to be filled.

Other: blood draw

Controls (adults)

Healthy adult controls Blood will be collected and a short questionnaire has to be filled.

Other: blood draw

Retinoblastoma survivors with Secondary primary malignancies

Adults that carry a RB1 germline mutation, were treated for retinoblastoma in the past, and are currently diagnosed with a secondary primary malignancy. Blood will be collected and a short questionnaire has to be filled. Tumor tissue will be collected during surgery.

Other: blood draw

Interventions

blood drawOTHER

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.

Controls (adults)Controls (children)Retinoblastoma patients (children)Retinoblastoma survivors (adults)Retinoblastoma survivors with Secondary primary malignancies

Eligibility Criteria

Age0 Years - 99 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

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.

You may qualify if:

  • Adult (16 years and older):
  • Group 1: germline mutation RB1.
  • Group 2 (control): no germline mutation RB1.
  • Pediatric (until 6 years of age):
  • Group 1: somatic or germline mutation RB1 and retinoblastoma.
  • Group 2 (control): no mutation RB1.

You may not qualify if:

  • Adult (16 years and older):
  • 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 (until 6 years of age):
  • Group 1: concomitant heritable (inherited) disorder other than caused by monoallelic mutation of RB1.
  • Group 2: cancer or already known cancer predisposition syndrome.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Institute Curie

Paris, France

Location

University Hospital Essen (UHE)

Essen, Germany

Location

Amsterdam UMC, location VUmc

Amsterdam, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

Serum, white blood cells, platelets, tissue

MeSH Terms

Conditions

RetinoblastomaNeoplasms

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Neoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueRetinal NeoplasmsEye NeoplasmsNeoplasms by SiteEye Diseases, HereditaryEye DiseasesRetinal Diseases

Intervention Hierarchy (Ancestors)

Specimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative Techniques

Study Officials

  • Armida Fabius

    VUMC

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

November 7, 2019

First Posted

November 15, 2019

Study Start

December 13, 2018

Primary Completion

March 31, 2023

Study Completion

March 31, 2023

Last Updated

July 25, 2023

Record last verified: 2023-07

Locations

DE(1)FR(1)NL(1)