rEECur - International Randomised Controlled Trial of Chemotherapy for the Treatment of Recurrent and Primary Refractory Ewing Sarcoma
The aim of the rEECur trial is to compare different chemotherapy regimens to determine which is most effective and/or has fewest side effects.
It is a randomised trial and is open to patients with a diagnosis of recurrent or primary refractory Ewing sarcoma (ES) from the age of two years old and will recruit 650 patients between 2015 and 2025.
The objective of rEECur is to identify the best treatment for recurrent and refractory Ewing sarcoma based on the balance between efficacy and toxicity.

Information for health professionals
- Background
rEECur is a Multi-Arm, Multi-Stage (MAMS) randomised phase II / phase III, open-label, international trial. Patients will be randomised at trial entry to receive one of the available regimens. Patients must be eligible for randomisation between at least two treatment arms to be eligible for trial entry.
For each arm, the phase II evaluation comprises two stages, with the number of patients needed being dependent on the design parameters. Because arms are introduced at different times, the evaluations will not occur simultaneously for all arms. At each assessment, the outcomes of contemporaneously randomised patients will be compared, and one arm will be dropped based on activity and/or toxicity. The remaining arms will continue to recruit. Arms that remain in the study after the required number of phase II patients have been recruited will progress to phase III evaluation. Patients recruited in the phase II stage for each comparison will contribute data to the phase III stage for that comparison.
Using the rolling MAMS design will allow the introduction of novel agents or regimens as new arms, if appropriate. The introduction of new arms will require a substantial amendment and approval by the relevant Competent Authority (the MHRA in the UK). An example of this is the addition of the CE arm which is currently being directly compared to IFOS.
- Protocols
Patient information and the trial protocol can be found on the CRCTU website.
- Recruitment status
- The GD arm is now closed to recruitment, following the first planned interim analysis. The outcomes of patients recruited to the GD arm were presented at ASCO 2019.
- The IT arm closed in March 2020.
- The TC arm closed in October 2021 as IFOS is likely to be more effective than TC at prolonging survival (95% probability).
Information for patients and carers
- Key facts
650 patients will be recruited from across Europe, Australia and New Zealand from 2015.
As of September 2022, the trial is recruiting patients at hospitals in the UK, Spain, Italy, Finland, Norway, Denmark, France, Hungary, Belgium, Poland, Czech Republic, Netherlands, Switzerland, New Zealand, Australia, Austria and Germany across many sites.
- Why is this trial running?
The trial initially compared four treatments, also known as regimens or arms, called TC, IT, GD and IFOS. These regimens were the four commonly used treatments for recurrent Ewing sarcoma. Three of the original four treatment arms have permanently closed (IT, GD and TC) on the basis that they had not shown sufficient evidence of activity based on response, progression-free survival and overall survival compared to Ifosfamide, (IFOS). We also introduced the Carboplatin and Etoposide (CE) arm to the study, which is currently being directly compared to IFOS. The trial is being run as it is not known which is the best treatment for this group of patients.
- Can I take part in the trial?
If you have Ewing sarcoma that has come back after treatment or have primary Ewing sarcoma that is not responding to therapy, you may be able to take part in the trial.
Talk about the trial with your doctor who will find out if you are eligible and if so, help you to take part.
- What treatment might I receive?
Ifosfamide (IFOS)
If you are in this group, you will receive four cycles of chemotherapy. This means that every three weeks you will have chemotherapy for five days in a row and this will happen four times. Once you have completed the four cycles your doctor may choose to give you some more treatment.
Carboplatin and Etoposide (CE)
If you are in this group, you will receive at least six cycles of chemotherapy. This means that every three weeks you will have chemotherapy for three days in a row and this will happen six times. Once you have completed the six cycles your doctor may choose to give you some more treatment, either more chemotherapy, radiotherapy or surgery.
- For more detailed information, please visit Cancer Research UK.
- Can I choose which treatment I receive?
No. rEECur is a randomised trial so you will be randomly assigned by computer. This means that the results of the trial are not biased in any way.
If you have any questions about this trial:
- Read more at Cancer Research UK
- Contact the Clinical Trials Unit at the University of Birmingham: reecur@trials.bham.ac.uk.
- The Trial Office cannot give advice on personal clinical questions.
Publications
- ASCO (2022) Phase III assessment of topotecan and cyclophosphamide and high-dose ifosfamide in rEECur: An international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES) [Abstract]
- ASCO (2020) Results of the second interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES) [Abstract]
- ASCO (2020) Correlation of response with progression-free (PFS) and overall (OS) survival in relapsed/refractory Ewing sarcoma (RR-ES): Results from the rEECur trial [Abstract]
- ASCO (2019) Results of the first interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma [Abstract]
Recruitment by 2018
While the trial data will not be analysed until the study closes, progress with the trial up to September 2018 is summarised below.
rEECur - recruitment by country
Country | Number of patients |
---|---|
United Kingdom | 84 |
Spain | 63 |
France | 53 |
Italy | 30 |
Hungary | 8 |
Denmarkk | 8 |
Norway | 3 |
Netherlands | 2 |
Czech Republic | 2 |
Belgium | 2 |
Poland | 1 |
Switzerland | 1 |
Finland | 1 |
rEECur - gender of patients
Gender | Number of patients |
---|---|
Male | 175 |
Female | 83 |
rEECur - age of patients
Age | Number of patients |
---|---|
Under 14 years | 50 |
14-25 years | 120 |
Over 25 years | 88 |