Groundbreaking trial launches for everyone with Ewing sarcoma

In many ways, Caitlin’s like any other 24-year-old. She’s close to her family, enjoys spending time with her friends and wants to travel to see more of the world.  

She also loves to exercise, so when she first started feeling pain in her left glute, she brushed it off, assuming she’d just pulled a muscle.  

When the pain eventually became unbearable, Caitlin’s girlfriend suggested a trip to the local A&E in Lewisham, London. Although her doctors didn’t think her condition was serious, they decided to run some tests just to be sure.  

Scans showed that Caitlin had a tumour, and the results of a later biopsy surprised both Caitlin and her medical team. She had Ewing sarcoma – a rare cancer that can occur in the bones or soft tissue and mainly affects children and young people. 

Symptoms for this type of cancer can be non-specific, like pain or swelling, meaning they can resemble those of other illnesses or even sports injuries, like in Caitlin’s case. And unlike some other cancers, such as breast cancer, Ewing sarcoma can develop in almost any part of the body, making the diagnosis process more complex.  

“I feel so lucky the hospital didn’t turn me away,” says Caitlin.

A new trial for all age groups

Soon after finding out she had cancer, Caitlin was assigned the standard treatment plan for Ewing sarcoma, which usually involves a combination of chemotherapy, radiotherapy and surgery.  

Unfortunately, this treatment protocol hasn’t changed much since the 1990s. That’s why, when Caitlin was offered a place on a brand-new Ewing sarcoma trial on her first day of chemotherapy, she accepted immediately.  

As the largest and most ambitious study ever conducted into Ewing sarcoma, INTER-EWING-1 aims to uncover new insights that could transform treatment options for everyone diagnosed with the disease.  

“What’s special about this trial is that we’re not excluding anyone based on their age,” says Professor Bernadette Brennan, Chief Investigator of INTER-EWING-1 and Consultant Paediatric Oncologist at the Royal Manchester Children’s Hospital.  

This age-inclusive approach is part of an exciting change currently taking place within clinical practice. Traditionally, many studies have set age restrictions for patients to be eligible to join a trial. For example, many adult trials set their lower age boundary at 18, excluding younger teenagers with the same cancer type. Meanwhile, trials into paediatric cancers often exclude those over the age of 18, even when older patients like Caitlin could benefit from the treatments they’re testing.  

Since 2018, Cancer Research UK has asked for scientific reasoning for age restrictions on trials, rather than relying on the traditional 18-year-old age cut-off. This should be particularly helpful for teenagers and those in their early 20s, although Brennan highlights that over-50s have also been excluded from previous Ewing sarcoma trials.  

As Ewing sarcoma primarily affects children and young people, INTER-EWING-1 will make the biggest impact for this age group. Nonetheless, the fact older patients are eligible to join means researchers can find out how well the treatments they’re looking at work for everyone who might need them. 

The science behind INTER-EWING-1

The first arm of INTER-EWING-1, which Caitlin is joining, will explore whether adding six further cycles of chemotherapy to standard treatment leads to better results.  

The second part of the trial will investigate what dose of radiotherapy treatment produces the best results in patients who cannot have surgery, as well as in those receiving radiotherapy after their tumour has been surgically removed.  

And the final arm will explore whether regorafenib, a medicine that has already shown success treating other types of sarcomas, can improve outcomes for newly diagnosed metastatic Ewing sarcoma patients. Metastatic cases occur when the cancer spreads to other parts of the body, and the prognosis for individuals with metastatic Ewing sarcoma is generally poor. The introduction of regorafenib in clinical trials marks a huge step forward in tackling Ewing sarcoma, as it’s the first time a targeted drug has ever been trialled as a first treatment option for this cancer type.  

“It’s important to find out if personalised medicine could play a role in treating Ewing sarcoma, but the molecular marker that’s present in most cases has so far been undruggable and untargetable,” explains Brennan.  

Brennan, who has dedicated her research career to coordinating trials of Ewing sarcoma treatments, believes regorafenib has the potential to overcome the disease’s ‘undruggability’. It works by blocking some of the signals cancer cells use to direct their growth, which means it can shrink tumours while sparing healthy tissue. For metastatic patients, regorafenib could be a more effective treatment with fewer potential side effects.  

“It’s important to say that the outcome is good for most patients already,” Brennan says. “That’s why we wanted to select the metastatic patients who had the most to benefit from a new drug. This is one of the first studies in Ewing sarcoma to offer a new treatment like this upfront.” 

Bigger and better

Brennan first started working on Ewing sarcoma trials in 1999. Over the years, she’s witnessed first-hand how dedicated research and funding have driven advancements for people with this type of cancer.  

In 2012, we contributed £500,000 to the Euro Ewing 2012 trial, which Brennan developed and ran. The results of this study helped establish a new European standard for treatment, ensuring all patients in Europe, including Caitlin, now receive the best chemotherapy regimen doctors can offer.  

Now we’re giving INTER-EWING-1, the successor to Euro Ewing 2012, £3m to build on past achievements and deepen our understanding of Ewing sarcoma. The dramatic increase in funding has allowed Brennan to broaden the scope of her work.  

“Traditionally, Ewing sarcoma trials in have very much focused on chemotherapy,” she says. Now, with additional resources, INTER-EWING-1 is also exploring radiotherapy and biomarkers – areas which have previously been overlooked. The radiotherapy arm of INTER-EWING-1 has specifically been designed to replicate what Euro Ewing 2012 did for chemotherapy and compare the approaches used in different countries to establish an evidence-based standard of care. 

The success of Euro Ewing 2012 has also helped INTER-EWING-1 attract interest from clinicians around the world.  

“An important aspect of INTER-EWING-1 is that it will also run in Australia and New Zealand, instead of being limited to Europe,” says Brennan. “It’s brought in a much bigger group of countries, and therefore patients, to take part.” 

International collaboration is essential for studying rare cancers like Ewing sarcoma, as individual countries often don’t have enough cases to be able to compare different treatment options and draw meaningful conclusions. By pooling data from around the world, Brennan and her fellow researchers will be better equipped to evaluate the success of regorafenib, different radiotherapy doses and maintenance chemotherapy.  

A personal decision

Choosing to take part in a clinical trial or enrol your child on a study can be a difficult decision.  

Caitlin, for one, didn’t hesitate to join the maintenance chemotherapy arm of INTER-EWING-1.  

On the flip side, those who have responded well to standard care may decide against joining a trial, feeling that their outcomes are already positive and unlikely to improve any further, even with additional experimental treatment.  

Whatever the patient’s (or parents’) view, Brennan emphasises the need for clear and compassionate communication during the trial recruitment process, so that people are able to make informed decisions either for themselves or on behalf of their children.  

What’s next for people with Ewing sarcoma?

Due to the groundbreaking potential of INTER-EWING-1, Brennan expects lots of interest from families and people of all ages who want to take part.  

We’ll be tracking how the trial develops over the coming years, eagerly awaiting its results. 

With Brennan and her team driving forward progress, we’re hopeful that INTER-EWING-1 could revolutionise treatment for Caitlin and all others affected by Ewing sarcoma.

Momoko