New Strategies to Detect Cancers in Carriers of Mutations in RB1

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 Status

Other

Estimated Enrollment

396

Start Date

December 13, 2018

Completion Date

May 31, 2022

Primary Completion Date

May 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

N/A - 99 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Armida Fabius, 0031-20-4444981, [email protected]

Location Countries

France

Location Countries

France

NCT ID

NCT04164134

Organization ID

129

Secondary IDs

NL8013

Responsible Party

Principal Investigator

Study Sponsor

VU University Medical Center

Collaborators

 University Hospital, Essen

Study Sponsor

Armida Fabius, Principal Investigator, VUMC

Verification Date

April 2021