rEECur

The aim of the rEECur trial is to compare different chemotherapy regimens to treat Ewing sarcoma that didn’t respond to treatment or has come back afterwards to determine which is the 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.  Patients will be recruited from across Europe, Australia and New Zealand from 2015.

The trial is being run as it is not known which is the best treatment for this group of patients. 

The trial initially compared four treatments, also known as regimens or arms, called TC (Topotecan and Cyclophospamide), IT (Irinotecan and Temozolomide), GD (Gemcitabine and Docetaxel) and IFOS (Ifosfamide). 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 introduced the CE (Carboplatin and Etoposide) arm as a 5th arm to the study, which was directly compared to IFOS. It closed in August 2024 on the basis that it showed a worse event free survival time and objective response outcome compared to IFOS. The trial is currently comparing the IFOS arm to a combination of Ifosfamide with Lenvatinib (IFOS-L). This 6th arm was introduced in June 2023. A 7th new arm is planned to be introduced next year. 

As of November 2025, the trial is open to recruitment at hospitals in the UK, Spain, Italy, Denmark, Switzerland, New Zealand, Australia and Austria. The trial is planned to open to recruitment in Finland, Norway, the Netherlands, Belgium and France in 2026.

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.

Eligibility

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.

• Ifosfamide

Ifosfamide and Lenvatinib (IFOS-L)

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. Alongside this you will be given capsules of Lenvatinib to take daily and continuously until the end of treatment. You can take the capsules at home. Once you have completed the four cycles of IFOS you many continue Lenvatinib treatment for up to two years.  

• Ifosfamide
• Lenvatinib

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.

Patients who take part in rEECur also have the option to contribute to biological studies alongside the trial by donating samples of their blood and any tumour tissue remaining from any biopsies that are collected as part of their diagnosis and monitoring of treatment. 

To date, over 2000 biospecimens have been collected from patients taking part in the trial. These will be used in research to help better understand the disease.

rEECur is a Multi-Arm, Multi-Stage (MAMS) randomised phase II / phase III, open-label, international trial. Patients are 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. 

Using the rolling MAMS design allows the introduction of novel agents or regimens as new arms, if appropriate. The introduction of new arms requires a substantial amendment/modification to the trial and approval by the relevant Competent Authority (the MHRA in the UK). An example of this is the addition of the CE arm which was directly compared to IFOS. 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. Where comparisons continue from phase II to phase III, patients recruited in the phase II stage will contribute data to the phase III assessment for that comparison.

• EudraCT number: 2014-000259-99
• ISRCTN reference number: ISRCTN 36453794
• rEECur trial schema (PDF)

Patient information and the trial protocol can be found on the CRCTU website.

• The GD arm closed in November 2018, 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, following the first planned interim analysis. The outcomes of patients recruited to the IT arm were presented at ASCO 2020.
• The TC arm closed in October 2021 as IFOS is likely to be more effective than TC at prolonging survival (95% probability). The outcomes of patients recruited to the TC arm were presented at ASCO 2022.
• The CE arm closed in August 2024 based on poorer survival outcomes compared to IFOS.  The outcomes of patients recruited to the CE arm were presented at ASCO 2025.
• Recruitment to the IFOS vs IFOS-L phase II comparison is ongoing and passed the interim assessment in June 2025.