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New Strategies to Detect Cancers in Carriers of Mutations in RB1 (NIRBTEST)

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ClinicalTrials.gov Identifier: NCT04164134
Recruitment Status : Recruiting
First Posted : November 15, 2019
Last Update Posted : April 2, 2021
Sponsor:
Collaborators:
University Hospital, Essen
Institut Curie
Ligue contre le cancer, France
Information provided by (Responsible Party):
Armida W. M. Fabius, VU University Medical Center

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.


Condition or disease Intervention/treatment
Retinoblastoma Secondary Primary Malignancies After Retinoblastoma Other: blood draw

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Study Type : Observational
Estimated Enrollment : 396 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: New Strategies to Detect Cancers in Carriers of Mutations in RB1: Blood Tests Based on Tumor-educated Platelets, or Extracellular Vesicles.
Actual Study Start Date : December 13, 2018
Estimated Primary Completion Date : May 31, 2022
Estimated Study Completion Date : May 31, 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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

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 (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

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.


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

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


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

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.





Primary Outcome Measures :
  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). [ Time Frame: blood will be taken at study inclusion, patients will be followed throughout the study, max 3 years and 9 months. ]
    blood analyses at time of inclusion to determine baseline


Secondary Outcome Measures :
  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. [ Time Frame: 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. ]
    Comparison of blood at time of inclusion and blood at time of SPM diagnosis versus tumor tissue (if available)


Biospecimen Retention:   Samples With DNA
Serum, white blood cells, platelets, tissue


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 99 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04164134


Contacts
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Contact: Armida Fabius, PhD 0031-20-4444981 a.fabius@vumc.nl

Locations
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France
Institute Curie Recruiting
Paris, France
Contact: Francois Doz, Prof. Dr.    0033-144324555    Francois.Doz@curie.fr   
Germany
University Hospital Essen (UHE) Recruiting
Essen, Germany
Contact: Petra Ketteler    0049-2017232255    Petra.ketteler@uk-essen.de   
Netherlands
Amsterdam UMC, location VUmc Recruiting
Amsterdam, Netherlands
Contact: Armida Fabius, PhD    0031-20-4444981    a.fabius@vumc.nl   
Sponsors and Collaborators
VU University Medical Center
University Hospital, Essen
Institut Curie
Ligue contre le cancer, France
Investigators
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Principal Investigator: Armida Fabius VUMC
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Responsible Party: Armida W. M. Fabius, Principal Investigator, VU University Medical Center
ClinicalTrials.gov Identifier: NCT04164134    
Other Study ID Numbers: 129
NL8013 ( Registry Identifier: Nederlands Trial Register )
First Posted: November 15, 2019    Key Record Dates
Last Update Posted: April 2, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Armida W. M. Fabius, VU University Medical Center:
Retinoblastoma
blood test
liquid biopsy
RB1
cancer
Secondary primary malignancies
SPM
Additional relevant MeSH terms:
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Neoplasms
Retinoblastoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Retinal Neoplasms
Eye Neoplasms
Neoplasms by Site
Eye Diseases, Hereditary
Eye Diseases
Retinal Diseases