RetinoblastomaNIRBTESTNCT04164134
New Strategies to Detect Cancers in Carriers of Mutations in RB1
An observational study of Retinoblastoma and Secondary Primary Malignancies After Retinoblastoma, run by Amsterdam UMC, location VUmc at 3 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Retinoblastoma, Secondary Primary Malignancies After Retinoblastoma
- What is being tested?
- blood draw
- How many people
- 378 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 13 Dec 2018to 31 Mar 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 99 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: New Strategies to Detect Cancers in Carriers of Mutations in RB1: Blood Tests Based on Tumor-educated Platelets, or Extracellular Vesicles.
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:
Read more
- 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.
- Being tested
- blood draw
- Keywords
- Retinoblastoma, blood test, liquid biopsy, RB1, cancer, Secondary primary malignancies, SPM
- Medical subject headings
- Retinoblastoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Other: blood draw | |
| Controls (adults) | Healthy adult controls Blood will be collected and a short questionnaire has to be filled. Receives: 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. Receives: Other: blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Comparison of blood at time of inclusion and blood at time of SPM diagnosis versus tumor tissue (if available)
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2019
- Study start13 Dec 2018
- Primary completion31 Mar 2023
- Study completion31 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RetinoblastomaStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 378 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Essen, Institut Curie, Ligue contre le cancer, France
- Responsible party
- Principal investigator, Armida W. M. Fabius, Amsterdam UMC, location VUmc
- Investigators
- Armida Fabius, Principal investigator, VUMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04164134
- Sponsor's protocol ID
- 129
- Other IDs
- NL8013
- Acronym
- NIRBTEST
- Status last verified
- Jul 2023
- First submitted
- 7 Nov 2019
- Last updated
- 25 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- New Strategies to Detect Cancers in Carriers of Mutations in RB1: Blood Tests Based on Tumor-educated Platelets, or Extracellular Vesicles.
- ClinicalTrials.gov ID
- NCT04164134
- Acronym / sponsor ID
- NIRBTEST / 129
- Keywords
- Retinoblastoma, blood test, liquid biopsy, RB1, cancer, Secondary primary malignancies, SPM
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 378 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- University Hospital, Essen, Institut Curie, Ligue contre le cancer, France
- Study start
- 13 Dec 2018 (actual)
- Primary completion
- 31 Mar 2023 (actual)
- Study completion
- 31 Mar 2023 (actual)
- First posted
- 15 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Retinoblastoma patients (children) | – | Other: blood drawChildren 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. |
| Controls (children) | – | Other: blood drawChildren 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. |
| Retinoblastoma survivors (adults) | – | Other: blood drawAdults 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. |
| Controls (adults) | – | Other: blood drawHealthy adult controls Blood will be collected and a short questionnaire has to be filled. |
| Retinoblastoma survivors with Secondary primary malignancies | – | Other: blood drawAdults 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. |
Who may qualify
- Ages
- 0 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- Group 1: germline mutation RB1.
- Group 2 (control): no germline mutation RB1.
- Group 1: somatic or germline mutation RB1 and retinoblastoma.
- Group 2 (control): no mutation RB1.
Key exclusion criteria (6 listed)
- Group 1: concomitant heritable (inherited) disorder other than caused by monoallelic mutation of RB1.
- Group 2 (control): cancer or already known cancer predisposition syndrome.
- Group 1: concomitant heritable (inherited) disorder other than caused by monoallelic mutation of RB1.
- Group 2: cancer or already known cancer predisposition syndrome.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood drawControl 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. | Other | Controls (adults), Controls (children), Retinoblastoma patients (children), Retinoblastoma survivors (adults), Retinoblastoma survivors with Secondary primary malignancies |
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).
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
1 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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Armida Fabius principal investigator
VUMC
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Retinoblastoma and Secondary Primary Malignancies After Retinoblastoma, run by Amsterdam UMC, location VUmc at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France, Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2023.