Condition category
Cancer
Date applied
09/01/2019
Date assigned
28/01/2019
Last edited
25/03/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

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 a routine biopsy/surgery to obtain tumour tissue.

What does the study involve?
Participants 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). 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. 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.

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 December 2021

Who is funding the study?
Cancer Research UK

Who is the main contact?
Amina Bukhari
Smpaeds@trials.bham.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Ms Amina Bukhari

ORCID ID

Contact details

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
+44 (0)121 414 7851
Smpaeds@trials.bham.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

40156

Study information

Scientific title

Stratified medicine paediatrics: genomic characterisation of relapsed paediatric cancers for diagnostics and stratified therapy

Acronym

SMPaeds

Study hypothesis

SMPaeds 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

London - Camden & Kings Cross Research Ethics Committee, NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, Tel: 0207 104 8086, Email: nrescommittee.london-camdenandkingscross@nhs.net

Study design

Non-randomised; Interventional; Design type: Screening, Diagnosis, Other

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Solid tumours, including lymphomas

Intervention

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

Phase

Drug names

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

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 trial start date

01/01/2018

Overall trial end date

31/12/2021

Reason abandoned (if study stopped)

Eligibility

Participant 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 type

Patient

Age group

Mixed

Gender

Both

Target number of participants

Planned Sample Size: 400; UK Sample Size: 400

Participant exclusion criteria

Does not meet inclusion criteria

Recruitment start date

01/02/2019

Recruitment end date

31/12/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Aberdeen’s Children Hospital
Westburn Road
Aberdeen
AB25 2ZG
United Kingdom

Trial participating centre

Royal Belfast Hospital for Sick Children
180 Falls Road
Belfast
BT12 6BE
United Kingdom

Trial participating centre

Birmingham Children's Hospital
Steelhouse Lane
Birmingham
B4 6NH
United Kingdom

Trial participating centre

Bristol Royal Hospital for Children
Uhbristol Education Centre
Bristol
BS2 8AE
United Kingdom

Trial participating centre

Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Noah’s Ark Children’s Hospital for Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

Royal Hospital for Sick Children Edinburgh
9 Sciennes Road
Edinburgh
EH9 1LF
United Kingdom

Trial participating centre

Royal Hospital for Children
1345 Govan Road
Glasgow
G51 4TF
United Kingdom

Trial participating centre

Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Alder Hey Children's Hospital
Eaton Road
Liverpool
L12 2AP
United Kingdom

Trial participating centre

Great Ormond Street Hospital for Children
Great Ormond Street
London
WC1N 3JH
United Kingdom

Trial participating centre

Royal Manchester Children’s Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom

Trial participating centre

Queen’s Medical Centre, Nottingham
University Hospital NHS Trust
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

John Radcliffe Hospital
Headley Way
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Sheffield Children's Hospital
Western Bank
Sheffield
S10 2TH
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

University College London Hospital
235 Euston Road
London
NW1 2BU
United Kingdom

Trial participating centre

Royal Marsden Hospital Sutton
Downs Road
Sutton
SM2 5PT
United Kingdom

Sponsor information

Organisation

Institute of Cancer Research, London

Sponsor details

c/o Dr Barbara Pittam
Director of Academic Services
123 Old Brompton Road
London
SW7 3RP
United Kingdom
+44 (0)20 7153 5360
barbara.pittam@icr.ac.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK; Grant Codes: C34648/A24566

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

CHILDREN with CANCER UK (Children with Leukaemia); Grant Codes: 17-325

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The protocol is not currently available online, but will be available soon.

IPD sharing statement
The datasets generated during or analysed during the current study will be available upon request from the SMPaeds 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.

Intention to publish date

31/12/2022

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

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.