An overarching study for children and adults with frontline and relapsed rhabdomyosarcoma
FaR-RMS is an over-arching study for children and adults with newly diagnosed and relapsed rhabdomyosarcoma (RMS), that started recruiting patients in 2019 and will end enrolling them in 2026. It is a multi-arm, multi-stage trial, involving several different questions regarding chemotherapy, local treatment, treatment at relapse or long term sequelae, among others.
The FaR-RMS trial is an overarching trial for all patients with newly diagnosed and relapsed paediatric-type rhabdomyosarcoma and is open to patients of all ages. The trial has an innovative multi-arm, multi-stage design that allows the testing of new combinations of therapy in upfront and relapsed settings in phase Ib, phase II and phase III.
The trial has now been open for over five years and is recruiting well, with 1,087 patients registered so far. The CT3 relapse research question opened in March 2022, funded by Bayer, and closed to recruitment in August 2025. The phase 1b question completed recruitment in November 2023, and the CT1a and CT1b induction chemotherapy randomisations subsequently opened in April 2024.
We are delighted that there is widespread international interest, and we continue to work with new countries to open the trial. The current recruiting countries are:
Number of open sites
Australia 11
Austria 5
Belgium 7
Czech Republic 2
Denmark 2
France 38
Germany 8
Greece 7
Ireland 1
Israel 6
Italy 1
Netherlands 2
New Zealand 2
Norway 5
Portugal 0
Slovenia 1
Spain 13
Sweden 8
Switzerland 9
United Kingdom 28
Countries still in set-up since last update:
Croatia, Finland, Slovakia, Singapore.
Phase 1b Dose Escalation Study – Recruitment Complete
The purpose of the Phase 1b question was to establish the dose of irinotecan in combination with ifosfamide, vincristine and actinomycin D. This question was open at ITCC and early phase approved centres. It completed recruitment in December 2023, following recruitment of 22 patients.
An abstract “Determining the recommended phase 2 dose (RP2D) of dose intense Irinotecan combined with IVA chemotherapy (IRIVA) in newly diagnosed very high risk rhabdomyosarcoma: a phase Ib study within the EpSSG Frontline and Relapsed Rhabdomyosarcoma Study (FaR-RMS)” was presented at the American Society of Clinical Oncology 2025 Annual Meeting, and a full manuscript of the Phase 1b data is in preparation.
Induction Chemotherapy (CT1a/b)
Following the completion of Phase 1b, the CT1 randomisations opened on 10-Apr-2024 via a non-substantial protocol amendment. These questions compare the determined dose of irinotecan (50mg/m2) in combination with ifosfamide, vincristine and actinomycin D, against the current standard of care for patients with High Risk and Very High Risk disease.
So far, 144 patients have been recruited to the CT1 induction questions.
Radiotherapy (RT1a/b/c, RT2)
The planned radiotherapy questions in FaR-RMS were: pre vs post-operative radiotherapy (RT1a), dose-escalation in patients at higher risk of local failure (RT1b for patients with resectable disease, RT1c for non-resectable disease) and comparing limited vs extensive radiotherapy for patients with extensive metastatic disease (RT2). An important aspect of the study focusses on the Quality of Life (QoL) of patients when receiving radiotherapy.
So far, 261 patients have been recruited to the Radiotherapy questions.
The RT1a and RT2 randomisations closed to recruitment on 21-Jul-2025. This decision follows consultation with the FaR-RMS Data Monitoring Committee (DMC), prompted by persistently low recruitment rates into RT1a and RT2. RT1a did not meet the feasibility endpoint specified in the protocol. No safety concerns have been identified in relation to these treatment arms. The QoL endpoints are being updated so that QoL questionnaires may still be collected.
Recruitment to the RT1b and RT1c radiotherapy randomisations was temporarily suspended on 11-Feb-2026. This is due to QUARTET being unable to provide Radiotherapy Quality Assurance (RTQA) at this time. We are currently working to resolve this issue and investigate other options to allow RT1b and RT1c to be re-opened as soon as possible.
Maintenance Chemotherapy (CT2a/b)
The purpose of the CT2 questions is to extend the number of maintenance chemotherapy cycles for patients with HR and VHR disease compared to the current standard of care i.e. 6 vs 12 cycles and 12 vs 24 cycles respectively. Please note that some younger patients may not be able to swallow cyclophosphamide capsules. Where sites need access to oral liquid formulations, this should be discussed with the National Coordinating Centres.
So far, 236 patients have been recruited to the Maintenance questions.
Relapsed RMS (CT3)
The CT3 relapse randomisation was closed to recruitment on 01-Aug-2025. Following a scheduled interim analysis, the DMC recommended discontinuation of the CT3 randomisation. This recommendation was based on the trial crossing the futility boundary, indicating a very low likelihood of demonstrating the protocol-defined 15% superiority of VIrR over VIrT. The Trial Steering Committee (TSC) endorsed the DMC’s recommendation. No safety concerns were identified in the interim data. At the point of closure, 116 sites across 14 countries had been activated to CT3 in total, and 106 patients were recruited.
Pathology
Risk group assignment and fusion status are integral parts of the trial, and molecular diagnostics for all cases of RMS should be carried out at the local centre. All samples will be centrally reviewed in each country by the National Pathology Coordinator. An international review of scanned slides is ongoing with over 612 cases having undergone international review for diagnostic surgery so far.
FDG-PET Sub-Study
If FDG PET-CT or FDG PET-MRI scanning is available at diagnosis & facilities allow, there is the option to take part in this sub study where an additional scan after 3 courses of induction chemotherapy is undertaken to determine the prognostic value of FDG-PET imaging response for EFS and local failure free survival. The collection of scans started in 2024 and is ongoing.
DW-MRI Sub-Study:
The aim of this sub-study is to investigate the prognostic value of DW-MRI imaging response by comparing DW-MRI at diagnosis and at reassessment (after 3 cycles of chemotherapy for patients with localised disease). Centres are encouraged to include diffusion-weighted series in their standard soft tissue sarcoma MRI protocols. Prinses Maxima and the EpSSG imaging group are leading this sub-study. The collection of scans started in 2024 and is ongoing.
Quality of Life (QoL)
A new set of sarcoma specific QoL questionnaires will be added to the next version of the Protocol. The Sarcoma Assessment Measure (SAM) is a QoL measure that was developed for teenage and adult patients. SAM-Paeds has more recently been developed using the same methodology. SAM-Paeds (self-report for patients age ≥8 to The aim is to extend the QoL study within FaR-RMS to correlate with a focus on the impact of local therapy (short- and longer-term outcomes). This will allow a more detailed understanding of the impact of local therapy for RMS for patients in the medium and long term. QoL questionnaires, including EORTC QLQ-C30, Peds-QL, SAM and SAM-Paeds will be collected from IRS III and IRS IV patients.
Surgery
This substudy will analyse the impact of surgery (as part of local control) on short term and late toxicity and Quality of Life. A surgical review of the data entry is ongoing.
Biology
This substudy will establish a virtual biobank for samples, including liquid biopsies, to evaluate prognostic factors at diagnosis, response to treatment and disease recurrence. The preferred storage of samples in is the VIVO biobank, Newcastle, UK, but some countries will use national biobanks. An upcoming protocol amendment will introduce specific biology questions into FaR-RMS.
Patient Videos
In collaboration with Alice’s Arc, patient and parent representatives and Enfuse, videos are being developed to help prospective patients understand the study. Initially a video on the radiotherapy randomisations has been developed, with a FaR-RMS overview video additionally planned. The format of the videos will allow translation into other languages.
The patient video can be viewed on the FaR-RMS Website: Far-RMS - University of Birmingham. It is planned to develop further patient videos in future.
EU-CTR Transition
The European Union Clinical Trials Regulation (EU-CTR) was implemented on 31st January 2022, and the FaR-RMS trial was required to transition to the Clinical Trials Information System (CTIS) by 31st January 2025 for EU regulatory approvals to remain valid. The FaR-RMS trial successfully completed transition of 17 countries’ ethical and competent authority approvals to the CTIS system on 15th November 2024. In order to fully comply with the updated regulations, a 1st amendment is in preparation for submission in 2026.
Planned Protocol Amendment 2026
The FaR-RMS Protocol is being amended with the following updates:
• Changes to inclusion criteria including:
• MYOD1 L122R mutations will allow risk group to be upstaged to Very High Risk
• Radiotherapy: Patients with tumours >5cm and IRS III / MYOD1 L122R mutations to be considered Higher Local Failure Risk
• Removal of specific requirement to have RTQA performed by QUARTET
• Quality of Life questionnaires SAM and SAM-Paeds will be implemented for consenting patients having radiotherapy and surgery
• Biology updates including:
• Addition of biology endpoints
• Collection of viably frozen tumour tissue where possible
• Additional liquid biopsy sampling timepoints at maintenance and relapse
• Compliance with EU-CTR
The trial has now been open for over five years and is recruiting well, with 1,087 patients registered so far. The CT3 relapse research question opened in March 2022, funded by Bayer, and closed to recruitment in August 2025. The phase 1b question completed recruitment in November 2023, and the CT1a and CT1b induction chemotherapy randomisations subsequently opened in April 2024.
We are delighted that there is widespread international interest, and we continue to work with new countries to open the trial. The current recruiting countries are:
Number of open sites
Australia 11
Austria 5
Belgium 7
Czech Republic 2
Denmark 2
France 38
Germany 8
Greece 7
Ireland 1
Israel 6
Italy 1
Netherlands 2
New Zealand 2
Norway 5
Portugal 0
Slovenia 1
Spain 13
Sweden 8
Switzerland 9
United Kingdom 28
Countries still in set-up since last update:
Croatia, Finland, Slovakia, Singapore.
Phase 1b Dose Escalation Study – Recruitment Complete
The purpose of the Phase 1b question was to establish the dose of irinotecan in combination with ifosfamide, vincristine and actinomycin D. This question was open at ITCC and early phase approved centres. It completed recruitment in December 2023, following recruitment of 22 patients.
An abstract “Determining the recommended phase 2 dose (RP2D) of dose intense Irinotecan combined with IVA chemotherapy (IRIVA) in newly diagnosed very high risk rhabdomyosarcoma: a phase Ib study within the EpSSG Frontline and Relapsed Rhabdomyosarcoma Study (FaR-RMS)” was presented at the American Society of Clinical Oncology 2025 Annual Meeting, and a full manuscript of the Phase 1b data is in preparation.
Induction Chemotherapy (CT1a/b)
Following the completion of Phase 1b, the CT1 randomisations opened on 10-Apr-2024 via a non-substantial protocol amendment. These questions compare the determined dose of irinotecan (50mg/m2) in combination with ifosfamide, vincristine and actinomycin D, against the current standard of care for patients with High Risk and Very High Risk disease.
So far, 144 patients have been recruited to the CT1 induction questions.
Radiotherapy (RT1a/b/c, RT2)
The planned radiotherapy questions in FaR-RMS were: pre vs post-operative radiotherapy (RT1a), dose-escalation in patients at higher risk of local failure (RT1b for patients with resectable disease, RT1c for non-resectable disease) and comparing limited vs extensive radiotherapy for patients with extensive metastatic disease (RT2). An important aspect of the study focusses on the Quality of Life (QoL) of patients when receiving radiotherapy.
So far, 261 patients have been recruited to the Radiotherapy questions.
The RT1a and RT2 randomisations closed to recruitment on 21-Jul-2025. This decision follows consultation with the FaR-RMS Data Monitoring Committee (DMC), prompted by persistently low recruitment rates into RT1a and RT2. RT1a did not meet the feasibility endpoint specified in the protocol. No safety concerns have been identified in relation to these treatment arms. The QoL endpoints are being updated so that QoL questionnaires may still be collected.
Recruitment to the RT1b and RT1c radiotherapy randomisations was temporarily suspended on 11-Feb-2026. This is due to QUARTET being unable to provide Radiotherapy Quality Assurance (RTQA) at this time. We are currently working to resolve this issue and investigate other options to allow RT1b and RT1c to be re-opened as soon as possible.
Maintenance Chemotherapy (CT2a/b)
The purpose of the CT2 questions is to extend the number of maintenance chemotherapy cycles for patients with HR and VHR disease compared to the current standard of care i.e. 6 vs 12 cycles and 12 vs 24 cycles respectively. Please note that some younger patients may not be able to swallow cyclophosphamide capsules. Where sites need access to oral liquid formulations, this should be discussed with the National Coordinating Centres.
So far, 236 patients have been recruited to the Maintenance questions.
Relapsed RMS (CT3)
The CT3 relapse randomisation was closed to recruitment on 01-Aug-2025. Following a scheduled interim analysis, the DMC recommended discontinuation of the CT3 randomisation. This recommendation was based on the trial crossing the futility boundary, indicating a very low likelihood of demonstrating the protocol-defined 15% superiority of VIrR over VIrT. The Trial Steering Committee (TSC) endorsed the DMC’s recommendation. No safety concerns were identified in the interim data. At the point of closure, 116 sites across 14 countries had been activated to CT3 in total, and 106 patients were recruited.
Pathology
Risk group assignment and fusion status are integral parts of the trial, and molecular diagnostics for all cases of RMS should be carried out at the local centre. All samples will be centrally reviewed in each country by the National Pathology Coordinator. An international review of scanned slides is ongoing with over 612 cases having undergone international review for diagnostic surgery so far.
FDG-PET Sub-Study
If FDG PET-CT or FDG PET-MRI scanning is available at diagnosis & facilities allow, there is the option to take part in this sub study where an additional scan after 3 courses of induction chemotherapy is undertaken to determine the prognostic value of FDG-PET imaging response for EFS and local failure free survival. The collection of scans started in 2024 and is ongoing.
DW-MRI Sub-Study:
The aim of this sub-study is to investigate the prognostic value of DW-MRI imaging response by comparing DW-MRI at diagnosis and at reassessment (after 3 cycles of chemotherapy for patients with localised disease). Centres are encouraged to include diffusion-weighted series in their standard soft tissue sarcoma MRI protocols. Prinses Maxima and the EpSSG imaging group are leading this sub-study. The collection of scans started in 2024 and is ongoing.
Quality of Life (QoL)
A new set of sarcoma specific QoL questionnaires will be added to the next version of the Protocol. The Sarcoma Assessment Measure (SAM) is a QoL measure that was developed for teenage and adult patients. SAM-Paeds has more recently been developed using the same methodology. SAM-Paeds (self-report for patients age ≥8 to The aim is to extend the QoL study within FaR-RMS to correlate with a focus on the impact of local therapy (short- and longer-term outcomes). This will allow a more detailed understanding of the impact of local therapy for RMS for patients in the medium and long term. QoL questionnaires, including EORTC QLQ-C30, Peds-QL, SAM and SAM-Paeds will be collected from IRS III and IRS IV patients.
Surgery
This substudy will analyse the impact of surgery (as part of local control) on short term and late toxicity and Quality of Life. A surgical review of the data entry is ongoing.
Biology
This substudy will establish a virtual biobank for samples, including liquid biopsies, to evaluate prognostic factors at diagnosis, response to treatment and disease recurrence. The preferred storage of samples in is the VIVO biobank, Newcastle, UK, but some countries will use national biobanks. An upcoming protocol amendment will introduce specific biology questions into FaR-RMS.
Patient Videos
In collaboration with Alice’s Arc, patient and parent representatives and Enfuse, videos are being developed to help prospective patients understand the study. Initially a video on the radiotherapy randomisations has been developed, with a FaR-RMS overview video additionally planned. The format of the videos will allow translation into other languages.
The patient video can be viewed on the FaR-RMS Website: Far-RMS - University of Birmingham. It is planned to develop further patient videos in future.
EU-CTR Transition
The European Union Clinical Trials Regulation (EU-CTR) was implemented on 31st January 2022, and the FaR-RMS trial was required to transition to the Clinical Trials Information System (CTIS) by 31st January 2025 for EU regulatory approvals to remain valid. The FaR-RMS trial successfully completed transition of 17 countries’ ethical and competent authority approvals to the CTIS system on 15th November 2024. In order to fully comply with the updated regulations, a 1st amendment is in preparation for submission in 2026.
Planned Protocol Amendment 2026
The FaR-RMS Protocol is being amended with the following updates:
• Changes to inclusion criteria including:
• MYOD1 L122R mutations will allow risk group to be upstaged to Very High Risk
• Radiotherapy: Patients with tumours >5cm and IRS III / MYOD1 L122R mutations to be considered Higher Local Failure Risk
• Removal of specific requirement to have RTQA performed by QUARTET
• Quality of Life questionnaires SAM and SAM-Paeds will be implemented for consenting patients having radiotherapy and surgery
• Biology updates including:
• Addition of biology endpoints
• Collection of viably frozen tumour tissue where possible
• Additional liquid biopsy sampling timepoints at maintenance and relapse
• Compliance with EU-CTR
Sponsor
The Study Sponsor is the University of Birmingham Cancer Research Clinical Trials, UK EudraCT Number: 2018-000515-24
(update June 2026)
