This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
31 Jul 202031 Aug 2026
Interventional
Intervention Type : Mixed
Intervention Description : FaR-RMS is an over-arching international study for patients with newly diagnosed and relapsed RMS including multiarm, multi-stage questions involving chemotherapy and radiotherapy, with no upper age limit.
Study EntryFaR-RMS includes a study entry point where all patients with RMS may give consent for the analysis of their biological samples and tumour pathology, alongside the collection of very basic patient characteristics, a treatment summary, and follow-up data for events.
Risk Group AllocationPatient disease status and risk group allocation will determine which randomisations they are eligible to enter. The risk group assignment is based on analyses performed on outcome data from the recent EpSSG-RMS2005 trial.
Treatment Questions (randomisation/Phase 1b registration)Patients may be entered into more than one treatment questions following study entry dependent on their disease status. Treatment questions may be available for patients with VHR, HR and Standard Risk (SR) disease. Separate consent is required for study entry and for each trial question. Newly diagnosed patients should, where possible, be entered into the FaR-RMS study at the time of initial diagnosis prior to receiving any chemotherapy. However, newly diagnosed patients can enter at the point of radiotherapy or maintenance, and those with relapsed disease can enter the study at the point of relapse even if not previously entered at initial diagnosis.
ConsentFor patients who appear to meet the criteria for participation in the study they and their parents/guardian (if applicable) will be approached by a Consultant or a delegated member of the research team working on this study. This trial will be explained to them and they will be given a copy of the age-specific Patient/Parent Information Sheets to read. The risks, benefits and alternatives to participating in this trial will be made clear to the patient/parent/guardian and they will be told that their participation is entirely voluntary and non-participation will not affect the care they subsequently receive from their medical team. If the patient/parent/guardian is satisfied with the information given and has had thechance to discuss the study with both the research team and their family and friends, they will be asked to sign a consent form for the study if they wish to participate.Age appropriate Information Sheets are available and there is a section on the Parent informed Consent Form where patients can document their assent if they wish to do so. For children who are not able to read, write or understand assent, the clinician will explain the trial in an age-appropriate manner and if verbal assent is given by the child it willbe documented in the patient’s medical records. Patients should be re-consented at the age of majority in accordance with national guidance/legislation.
Screening assessmentsA histologically confirmed diagnosis of RMS is required for Study Entry. It is strongly encouraged for molecular diagnostic results to be obtained prior to study entry to allow for a patient to be assigned to the correct risk group. The diagnosis and RMS subtyping will be performed by the local pathologist, although should this not be possible, thesample can be sent to the National Pathology Coordinator for an urgent review. For all patients, a formalin fixed paraffin embedded block together with a pseudo- anonymised Pathology report, if available, and molecular results, if available, will be sent to the National Pathology Coordinator as soon as possible after diagnosis for a retrospectivereview. The majority of screening assessments are standard of care, and will include blood tests, urine tests, physical exam, and tests to assess disease status: bone marrow examination, a lumbar puncture, scans (e.g. CT, MRI, PET-CT).
Phase 1b dose-finding study:This will be the first part of the study to open for newly diagnosed patients. The phase 1b irinotecan dose-finding study will investigate the addition of irinotecan to IVA (ifosfamide, vincristine and actinomycin D) chemotherapy (IrIVA). Up to 9 cycles in total will be given to each patient if tolerated. Dose-limiting toxicities (DLTs) will be assessed in Cycles 1 and 2. In the event that a patient experiences a DLT in cycle 1 or cycle 2, irinotecan will be stopped and the patient will continue with IVA as the standard of care. The Data MonitoringCommittee (DMC) will meet after each cohort has been recruited and DLTs assessed to ensure the ongoing safety of the trial.
Induction chemotherapy for newly diagnosed patients:Once the recommended phase II dose has been established, CT1A and CT1B randomisations will open. CT1A is for newly diagnosed VHR patients, and CT1B is for HR patients. The first 6 patients > 18 years randomised to IrIVA (from either CT1B or CT1A) will be carefully evaluated by the DMC before continuing the randomisation in adult patients toenhance the oversight of adult patients. In the CT1A randomisation, patients will be randomised to receive either IVADo (Ifosfamide, Vincristine, Actinomycin D,Doxorubicin) or IrIVA; in CT1B, they will be randomised to IVA or IrIVA. Cycles of chemotherapy will be given at 21-day intervals.
Radiotherapy for newly diagnosed disease:This trial also contains several radiotherapy randomisations for patients with newly diagnosed RMS.For patients with resectable disease (disease that can be removed by surgery), there is an RT1A randomisation in which patients will receive radiotherapy either before or after surgery. For those at a higher risk of local failure, they are then eligible to enter a second randomisation, RT1B, in which they will be randomised to receive either 41.4 Gy (standard of care dose) or 50.4 Gy (dose escalated radiotherapy).For those with non-resectable disease and an incomplete response who are also at a higher risk of local failure, there is also a radiotherapy dose randomization, RT1C, in which the patient will be randomised to receive either to 50.4 Gy (standard of care dose) or 59.4 Gy (dose escalated dose).For those with unfavourable metastatic disease there is the RT2 randomisation in which the patient will be randomised to either receive radiotherapy treatment to all sites of disease including metastatic sites, or radiotherapy treatment to the primary site and involved regional lymph nodes alone. For both this randomisation and the RT1Arandomisation, patients will be asked to complete a Health-Related Quality of Life questionnaire.All sites and patients participating in the radiotherapy questions will participate in the Radiotherapy Quality Assurance programme, facilitated via the SIOPE QUARTET (Quality and Excellence in Radiotherapy and Imaging for Children and Adolescents with Cancer across Europe in Clinical Trials) initiative. All sites will be required to be approved forradiotherapy delivery via QUARTET, and radiotherapy plans for each individual patient will be uploaded to the online system for approval. There will also be a retrospective Quality Control review of all scans and cross-sectional imaging received as part of the radiotherapy QA review process.
Maintenance Chemotherapy:VHR patients will receive 12 cycles of maintenance chemotherapy as standard of care; HR patients receive 6 cycles. VHR patients may then be eligible for the CT2A randomisation in which they will either stop treatment or receive 12 further cycles of maintenance chemotherapy, and HR patients for the CT2A randomisation where they will stop orreceive an additional 6 cycles. The chemotherapy for both randomisations is vinorelbine and cyclosphosphamide (VnC) and the cycles are each 28 days. Vinorelbine can be given in either an intravenous or oral format.
Chemotherapy for patients with relapsed disease:Patients with relapsed disease will be randomised to receive either VIr (Vincristine, Irinotecan) or VIrT (Vincristine, Irinotecan, Temozolomide). Cycles of chemotherapy will be given at 21-day intervals and up to 12 cycles will be given.
FDG PET-CT sub-study:This study will also encourage an FDG PET-CT or FDG PET-MRI scan after 3 courses of induction chemotherapy to determine prospectively its prognostic value. Should this not be standard of care, the patient will be asked to consent in the optional sub-study.
Follow-up:Following completion of treatment, the frequency of follow-up assessments should be as per local practice. However, every 3 months for the first 3 years and every 6 months thereafter is suggested. Patients will be followed-up for a minimum of 3 years, until the last patient has been followed-up for 3 years.
Rolling design:FaR-RMS has been designed to be a rolling programme of research, new treatment arms will be introduced dependant on emerging data and innovation, provided it is within the pre-defined research remit of the trial. A maximum of three new arms will be added to each of the frontline (VHR and HR) and relapse randomisations; and amaximum of four new arms to the Phase 1b component.
You can take part if:
You may not be able to take part if:
Phase 1b specific exclusion:1. Weight <10kg2. Active > grade 2 diarrhoea3. Prior allo- or autologous Stem Cell Transplant4. Uncontrolled inter-current illness or active infection5. Pre-existing medical condition precluding treatment6. Known hypersensitivity to any of the treatments or excipients7. Second malignancy8. Pregnant or breastfeeding women9. Urinary outflow obstruction that cannot be relieved prior to starting treatment10. Active inflammation of the urinary bladder (cystitis)
CT1a and CT1b specific exclusion:1. Active > grade 2 diarrhoea2. Prior allo- or autologous Stem Cell Transplant3. Uncontrolled inter-current illness or active infection4. Pre-existing medical condition precluding treatment5. Known hypersensitivity to any of the treatments or excipients6. Second malignancy7. Pregnant or breastfeeding women8. Urinary outflow obstruction that cannot be relieved prior to starting treatment9. Active inflammation of the urinary bladder (cystitis)
Radiotherapy specific exclusion1. Prior allo- or autologous Stem Cell Transplant2. Second malignancy3. Pregnant or breastfeeding women4. Receiving radiotherapy as brachytherapy
CT2a and CT2b specific exclusion:1. Prior allo- or autologous Stem Cell Transplant2. Uncontrolled inter current illness or active infection3. Second malignancy4. Pregnant or breastfeeding women5. Urinary outflow obstruction that cannot be relieved prior to starting treatment6. Active inflammation of the urinary bladder (cystitis)
CT3 specific exclusion:1. Active > grade 2 diarrhoea2. Prior allo- or autologous Stem Cell Transplant3. Uncontrolled inter-current illness or active infection4. Pre-existing medical condition precluding treatment5. Known hypersensitivity to any of the treatments or excipients6. Second malignancy7. Pregnant or breastfeeding women
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Cambridge University Hospitals NHS Foundation Trust
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
Oxford University Hospitals NHS Foundation Trust
John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9DU
NHS Lothian
Waverley Gate
2-4 Waterloo Place
Edinburgh
EH1 3EG
Cardiff & Vale University LHB
Corporate Headquarters
Heath Park
Cardiff
CF14 4XW
University Hospital Southampton NHS Foundation Trust
Mailpoint 18
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
NHS Greater Glasgow and Clyde
J B Russell House
Gartnavel Royal Hospital
1055 Great Western Road
Glasgow
G12 0XH
The Christie NHS Foundation Trust
550 Wilmslow Road
Withington
Manchester
M20 4BX
University College London Hospitals NHS Foundation Trust
250 Euston Road
London
NW1 2PG
Nottingham University Hospitals NHS Trust - Queen's Medical Centre Campus
Nottingham University Hospital
Derby Road
Nottingham
NG7 2UH
Leeds Teaching Hospitals NHS Trust
St. James's University Hospital
Beckett Street
Leeds
LS9 7TF
NHS Grampian
Summerfield House
2 Eday Road
Aberdeen
AB15 6RE
Manchester University NHS Foundation Trust
Cobbett House
Oxford Road
Manchester
M13 9WL
University Hospitals of Leicester NHS Trust
Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
University Hospitals Bristol NHS Foundation Trust
Marlborough Street
Bristol
BS1 3NU
The Royal Marsden NHS Foundation Trust
Fulham Road
London
SW3 6JJ
Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Freeman Hospital
Freeman Road
High Heaton
Newcastle-upon-Tyne
NE7 7DN
Great Ormond Street Hospital for Children NHS Foundation Trust
Great Ormond Street
London
WC1N 3JH
Birmingham Women's and Children's NHS Foundation Trust
Steelhouse Lane
Birmingham
B4 6NH
Nottingham University Hospitals NHS Trust - City Campus
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
Alder Hey Children's NHS Foundation Trust
Alder Hey Hospital
Eaton Road
West Derby
Liverpool
L12 2AP
Sheffield Children's NHS Foundation Trust
Western Bank
Sheffield
S10 2TH
This information has not yet been provided by the study team. You'll have an opportunity to discuss any risks and benefits that may be associated with this study prior to consenting to taking part.
