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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

Tracking Information
First Submitted Date November 7, 2019
First Posted Date November 15, 2019
Last Update Posted Date April 2, 2021
Actual Study Start Date December 13, 2018
Estimated Primary Completion Date May 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: November 12, 2019)
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
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: November 12, 2019)
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)
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
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.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Serum, white blood cells, platelets, tissue
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.

Condition
  • Retinoblastoma
  • Secondary Primary Malignancies After Retinoblastoma
Intervention 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.

Study Groups/Cohorts
  • 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.
    Intervention: 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.
    Intervention: 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.

    Intervention: Other: blood draw
  • Controls (adults)
    Healthy adult controls Blood will be collected and a short questionnaire has to be filled.
    Intervention: 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.

    Intervention: Other: blood draw
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: November 12, 2019)
396
Original Estimated Enrollment Same as current
Estimated Study Completion Date May 31, 2022
Estimated Primary Completion Date May 31, 2022   (Final data collection date for primary outcome measure)
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.
Sex/Gender
Sexes Eligible for Study: All
Ages up to 99 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Armida Fabius, PhD 0031-20-4444981 a.fabius@vumc.nl
Listed Location Countries France,   Germany,   Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number NCT04164134
Other Study ID Numbers 129
NL8013 ( Registry Identifier: Nederlands Trial Register )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Armida W. M. Fabius, VU University Medical Center
Study Sponsor VU University Medical Center
Collaborators
  • University Hospital, Essen
  • Institut Curie
  • Ligue contre le cancer, France
Investigators
Principal Investigator: Armida Fabius VUMC
PRS Account VU University Medical Center
Verification Date April 2021