Stratified Medicine Paediatrics (StratMedPaeds) - a study looking at genetic changes in children’s cancer
| ISRCTN | ISRCTN21731605 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN21731605 |
| IRAS number | 246557 (England, Wales, NI), 264925 (Scotland) |
| Secondary identifying numbers | CPMS 40156, IRAS 246557 (England, Wales, NI), 264925 (Scotland) |
- Submission date
- 09/01/2019
- Registration date
- 28/01/2019
- Last edited
- 07/02/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English Summary
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-the-genetics-of-childrens-cancer-stratmedpaediatrics (added 07/12/2020)
Background and study aims
This is a UK research study testing tumour (somatic) and normal (germline) DNA and RNA for genetic and gene-expression changes in children, teenagers and young adults with relapsed/refractory cancer. The aim of this study is to identify patients who may be eligible for new targeted anti-cancer therapies. The study will aid research that will help us to more precisely diagnose cancer and understand why some patients do not respond to standard treatments.
Who can participate?
UK children and young adults whose cancer has either come back (relapsed) or not responded to treatment (refractory) and have undergone or will undergo a routine biopsy/surgery to obtain tumour tissue or bone marrow.
What does the study involve?
Participants with a solid tumour provide a blood sample and a piece (or pieces, if available) of tumour collected from their most recent biopsy or surgery, or some of the tumour sample from the original cancer diagnosis ( if the hospital still has it). Participants with leukaemia provide a bone marrow sample. The results of the tests are relayed back to the patient’s doctor via an expert group of doctors who make recommendations on any available treatments. Patients and/or their parents are asked in advance to consider what information they which to receive in relation to any abnormal genetic results either in the tumour or their normal (germline) genetic code. In addition, the data collected is used and shared for the purposes of clinical research.
What are the possible benefits and risks of participating?
There may not be any individual benefit for the patient and the greatest benefits of the study may not be expected for several years and therefore will predominantly help future patients. However, should something be found in the genetic information of the tumour sample which may help in the understanding or treatment of the patient’s cancer (for example, it may provide a treatment option i.e. clinical trial); then the patient’s clinical team will be able to use this information. For solid tumour patients, as the tumour sample will already have been or is due to be taken as part of the care at the hospital, the patient will have only one blood test taken. The discomfort of this blood test is just like any other blood test. For leukaemia patients, the bone marrow sample will already have been or is due to be taken as part of the care at the hospital.
Where is the study run from?
1. Royal Aberdeen’s Children Hospital
2. Royal Belfast Hospital for Sick Children
3. Birmingham Children's Hospital
4. Bristol Royal Hospital for Children
5. Addenbrooke's Hospital
6. Noah’s Ark Children’s Hospital for Wales
7. Royal Hospital for Sick Children Edinburgh
8. Royal Hospital for Children
9. Leeds General Infirmary
10. Leicester Royal Infirmary
11. Alder Hey Children's Hospital
12. Great Ormond Street Hospital for Children
13. Royal Manchester Children’s Hospital
14. Royal Victoria Infirmary
15. Queen’s Medical Centre, Nottingham
16. John Radcliffe Hospital
17. Sheffield Children's Hospital
18. Southampton General Hospital
19. University College London Hospital
20. Royal Marsden Hospital Sutton
When is the study starting and how long is it expected to run for?
January 2018 to April 2027
Who is funding the study?
Cancer Research UK
Who is the main contact?
Amina Bukhari
Smpaeds@trials.bham.ac.uk
Contact information
Scientific
Trial Coordinator
Children’s Cancer Trials Team
Cancer Research UK Clinical Trials Unit Institute of Cancer and Genomic Sciences
The University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
| Phone | +44 (0)121 414 7851 |
|---|---|
| Smpaeds@trials.bham.ac.uk |
Study information
| Study design | Non-randomized; Interventional; Design type: Screening, Diagnosis, Other |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Stratified medicine paediatrics: genomic characterisation of relapsed paediatric cancers for diagnostics and stratified therapy |
| Study acronym | StratMedPaeds / SMPaeds |
| Study hypothesis | StratMedPaeds is a UK research study testing tumour (somatic) and normal (germline) DNA and RNA for genetic and gene-expression changes in children, teenagers and young adults with relapsed/refractory cancer. The results of the tests performed will identify patients who may be eligible for new targeted anti-cancer therapies and will aid research that will help us to more precisely diagnose cancer and understand why some patients do not respond to standard treatments. |
| Ethics approval(s) | London - Camden & Kings Cross Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, UK; +44 (0)207 104 8086; nrescommittee.london-camdenandkingscross@nhs.net), ref: not provided |
| Condition | Solid tumours (including lymphomas) or leukaemia |
| Intervention | Current interventions as of 15/03/2023: Patients with clinically relapsed/refractory progressive solid tumours (including brain and lymphomas) or leukaemia who undergo a biopsy as part of their standard of care are eligible for StratMedPaeds. Following receipt of valid informed consent, the patient can be registered in the central RDE database (MARVIN). In parallel, FFPE and FF tissue from the current relapse/refractory episode, along with blood and matching material from any previous diagnosis /tumour for solid tumour patients or Bone Marrow aspirate and Cerebrospinal fluid (CSF) if available, from the current relapse/refractory episode for leukaemia patients should be submitted to the central sample hub at Great Ormond Street Hospital for Children. For each patient, a mixture of techniques will be used, depending on the availability and quality of the DNA, and primary cancer diagnosis and previous testing. On tumour biopsy material - possible on Formalin fixed paraffin embedded (FFPE) and Bone Marrow/CSF 1. Customised next-generation sequencing panels (NGS panels) 2. Methylation sequencing On tumour biopsy material – Fresh Frozen 1. Whole exome sequencing (WES) 2. RNA-sequencing (RNASeq) 3. Low coverage whole genome sequencing (lcWGS) From blood: circulating tumour DNA (ctDNA) 1. NGS panel testing 2. Digital PCR From blood collected for germline analysis 1. Exome or genome sequencing _____ Previous interventions: Patients with clinically relapsed/refractory progressive solid tumours (including brain and lymphomas) who undergo a biopsy as part of their standard of care are eligible for SMPaeds. Following receipt of valid informed consent, the patient can be registered in the central RDE database (MARVIN). In parallel, FFPE and FF tissue from the current relapse/refractory episode, along with blood and matching material from any previous diagnosis/tumour should be submitted to the central sample hub at Great Ormond Street Hospital for Children. For each patient, a mixture of techniques will be used, depending on the availability and quality of the DNA, and primary cancer diagnosis and previous testing. On tumour biopsy material - possible on Formalin fixed paraffin embedded (FFPE): 1. Customised next-generation sequencing panels (NGS panels) 2. Methylation sequencing On tumour biopsy material – Fresh Frozen 1. Whole exome sequencing (WES) 2. RNA-sequencing (RNASeq) 3. Low coverage whole genome sequencing (lcWGS) From blood: circulating tumour DNA (ctDNA) 1. NGS panel testing 2. Digital PCR From blood collected for germline analysis 1. Exome or genome sequencing |
| Intervention type | Other |
| Primary outcome measure | The proportion of cases referred that receive a Molecular Tumour Board Report within 28 days |
| Secondary outcome measures | Outcomes to be achieved within a timescale of up to 3 years: 1. The number and proportion of samples successfully analysed 2. The reasons for analysis failure 3. The proportion of patients with known or unknown somatic molecular alterations 4. The proportion of patients with actionable molecular alterations in tumours 5. The proportion of patients in which any treatment recommendation can be made 6. The proportion of patients in which a treatment recommendation with a molecularly targeted therapy can be made 7. The proportion of patients successfully registered on to clinical trials 8. The proportion of patients successfully registered on to clinical trials of molecularly targeted therapies 9. The proportion of patients who have their diagnosis changed following multi-omic analysis 10. Progression Free Survival (PFS) 11. Any complications of biopsy 12. The proportion of patients with germline events 13. The proportion of patients recommended for clinical genetics service referral 14. Collection of data on individual genomic, epigenomic and transcriptomic characteristics of refractory/relapsed paediatric malignancies (added 15/03/2023) 15. The number and proportion of leukaemia samples successfully analysed on the DRP platform 16. The number and proportion of patients with leukaemia who have a potential therapy identified through the DRP platform Numerical data will be taken from the case report forms from each participating hospital site. Case report forms will be completed using information taken from the patient’s medical record. |
| Overall study start date | 01/01/2018 |
| Overall study end date | 30/04/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Sex | Both |
| Target number of participants | Planned Sample Size: 550; UK Sample Size: 550 |
| Total final enrolment | 806 |
| Participant inclusion criteria | Current inclusion criteria as of 15/03/2023: 1. Patients with a relapsed or refractory paediatric tumour (all solid tumours, central nervous system (CNS) tumours and lymphoma) or leukaemia 2. For solid tumours: Formalin fixed paraffin embedded (FFPE) tumour available from a biopsy, resection or other surgical procedure that was taken within 8 weeks of trial entry* 3. For leukaemia: Viable fresh or frozen Bone Marrow aspirate sample taken at a prior assessment within 8 weeks prior to trial entry** 3. Written informed consent of patient/parent/guardian/legal guardian*** * To allow full multi-omic analysis both fresh frozen and Formalin fixed paraffin embedded (FFPE) tumour plus a blood sample for constitutional (germline) and circulating tumour (ct) DNA will need to be available. Original diagnostic slides should be submitted at the same time as block from current relapse/refractory episode either in same shipment. ** Where available, a cerebrospinal fluid (CSF) sample in the event of an isolated or combined CNS relapse should also be provided in addition to the bone marrow aspirate. *** Some adult patients with brain tumours or brain metastases may be incapable of providing their own consent due to the neurological effects of their disease. In such cases, these patients will be classed as an incapacitated adult and a consultee will be sought. _____ Previous inclusion criteria: 1. Patients with a relapsed or refractory paediatric tumour (all solid tumours, central nervous system (CNS) tumours and lymphoma) 2. Formalin fixed paraffin embedded (FFPE) tumour available from a biopsy, resection or other surgical procedure that was taken within 8 weeks of trial entry* 3. Written informed consent of patient/parent/guardian/legal guardian** * To allow full multi-omic analysis both fresh frozen and Formalin fixed paraffin embedded (FFPE) tumour plus a blood sample for constitutional (germline) and circulating tumour (ct) DNA will need to be available. Original diagnostic slides should be submitted at the same time as block from current relapse/refractory episode either in same shipment or via PathXL (see laboratory manual for further details). ** Some adult patients with brain tumours or brain metastases may be incapable of providing their own consent due to the neurological effects of their disease. In such cases, these patients will be classed as an incapacitated adult and a consultee will be sought. |
| Participant exclusion criteria | Does not meet inclusion criteria |
| Recruitment start date | 01/02/2019 |
| Recruitment end date | 31/01/2024 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Aberdeen
AB25 2ZG
United Kingdom
Belfast
BT12 6BE
United Kingdom
Birmingham
B4 6NH
United Kingdom
Bristol
BS2 8AE
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Edinburgh
EH9 1LF
United Kingdom
Glasgow
G51 4TF
United Kingdom
Leeds
LS1 3EX
United Kingdom
Leicester
LE1 5WW
United Kingdom
Liverpool
L12 2AP
United Kingdom
London
WC1N 3JH
United Kingdom
Manchester
M13 9WL
United Kingdom
Newcastle upon Tyne
NE1 4LP
United Kingdom
Nottingham
NG7 2UH
United Kingdom
Oxford
OX3 9DU
United Kingdom
Sheffield
S10 2TH
United Kingdom
Southampton
SO16 6YD
United Kingdom
London
NW1 2BU
United Kingdom
Sutton
SM2 5PT
United Kingdom
Sponsor information
Research organisation
c/o Emma Pendleton
Director of Research Services
123 Old Brompton Road
London
SW7 3RP
England
United Kingdom
| Phone | +44 (0)20 7153 5360 |
|---|---|
| emma.pendleton@icr.ac.uk | |
"ROR" |
https://ror.org/043jzw605 |
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/04/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The protocol is not currently available online, but will be available soon. |
| IPD sharing plan | The datasets generated during or analysed during the current study will be available upon request from the StratMedPaeds Trial office (smpaeds@trials.bham.ac.uk). Type of data: Data on the distribution and frequency (incidence/prevalence) of molecular alterations at time of diagnosis and relapse, clinical diagnosis, treatment and clinical outcomes data. When the data will become available and for how long: : after publication, Indefinitely By what access criteria data will be shared including with whom: data may be shared with external investigators who wish to share clinical trial data. All requests for data sharing are dealt with on a case by case basis On receipt of a valid request to share data the trialists will ensure that: 1. External parties and trial oversight committees (e.g. Trial Steering Committee) are supportive of the request 2. The necessary legal, ethical and regulatory permissions to allow data sharing are in place 3. Anonymised data can be supplied 4. There is sufficient resource with to deal with the request For what types of analyses: all requests for data analyses will be reviewed. By what mechanism: Any request to share data should be submitted in writing to the Trial Management Group. The request should clearly document: 1. The scientific rationale of the proposal 2. Aims and objectives 3. Outcome measures 4. Data variables required 5. How the data will be analysed 6. Indicate what acknowledgements will be made on any publications resulting from the work. Whether consent from participants was obtained: either the patient, parent, guardian or consultee will have read and filled out a form giving written consent to take part in the SMPaeds study, this includes consent for the use of, and sharing of data, for research, teaching, commercial and scientific publications. Comments on data anonymisation: all data is subject to the General Data Protection Regulation and Data Protection Act 2018 for health and care research and will be kept strictly confidential. Identifiable information will be removed from the data and replaced by unique codes. The only exception to this is the signed informed consent form which is not anonymised in order to perform monitoring of the consent process. Any ethical or legal restrictions: if the above conditions are met we will provide the requested data. In some circumstances this may be subject to a Data Sharing Agreement being put in place. Please note: data sharing will usually only be considered once the primary endpoint data has been published in a peer reviewed journal. |
Editorial Notes
07/02/2025: Sponsor details updated. Total final enrolment added.
09/01/2024: The plain English summary was updated with the new study dates.
27/10/2023: The following changes were made to the study record:
1. The recruitment end date was changed from 31/10/2023 to 31/01/2024.
2. The overall study end date was changed from 31/10/2023 to 30/04/2027.
3. The intention to publish date was changed from 31/10/2023 to 30/04/2027.
4. IRAS numbers added.
15/03/2023: The following changes were made to the trial record:
1. The abbreviation 'SMPaeds' was changed to 'StratMedPaeds' in the public title, acronym, study hypothesis, interventions, plain English summary.
2. The overall end date was changed from 31/03/2023 to 31/10/2023.
3. The conditions was changed from "Solid tumours, including lymphomas" to "Solid tumours (including lymphomas) or leukaemia".
4. The interventions were changed.
5. The secondary outcome measures were changed.
6. The inclusion criteria were changed.
7. The target number of participants was changed from 400 to 550.
8. The recruitment end date was changed from 31/03/2022 to 31/10/2023.
9. The intention to publish date was changed from 31/12/2022 to 31/10/2023.
10. The plain English summary was updated to reflect these changes.
31/08/2022: The overall end date was changed from 31/03/2022 to 31/03/2023.
20/09/2021: Internal review.
09/06/2021: The overall trial end date has been changed from 31/08/2021 to 31/03/2022 and the plain English summary has been updated accordingly.
09/12/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2020 to 31/03/2022.
2. The overall trial end date was changed from 31/03/2022 to 31/08/2021.
07/12/2020: A link to a plain English summary on Cancer Research UK was added.
24/11/2020: The following changes were made to the trial record:
1. The recruitment resumed.
2. The overall end date was changed from 31/12/2021 to 31/03/2022.
20/04/2020: Due to current public health guidance, recruitment for this study has been paused as of 20/03/2020.
25/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Children's Cancer and Leukaemia; Health Category: Cancer and neoplasms; Disease/Condition: Malignant neoplasms of ill-defined, secondary and unspecified sites" to "Solid tumours, including lymphomas" following a request from the NIHR.
