Brief Title
New Strategies to Detect Cancers in Carriers of Mutations in RB1
Official Title
New Strategies to Detect Cancers in Carriers of Mutations in RB1: Blood Tests Based on Tumor-educated Platelets, or Extracellular Vesicles.
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.
Study Type
Observational
Primary Outcome
RNA expression on platelets and allelic DNA balance of EVs in the blood of adult RB1 mutation carriers (Rb-survivors) and retinoblastoma patients (children).
Secondary Outcome
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.
Condition
Retinoblastoma
Intervention
blood draw
Study Arms / Comparison Groups
Retinoblastoma patients (children)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Other
Estimated Enrollment
396
Start Date
December 13, 2018
Completion Date
October 31, 2022
Primary Completion Date
October 31, 2022
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Gender
All
Ages
0 Years - 99 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Armida Fabius, 0031-20-4444981, [email protected]
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT04164134
Organization ID
129
Secondary IDs
NL8013
Responsible Party
Principal Investigator
Study Sponsor
Amsterdam UMC, location VUmc
Collaborators
University Hospital, Essen
Study Sponsor
Armida Fabius, Principal Investigator, VUMC
Verification Date
April 2022