CaboGIST (EORTC 1317)

• Research type

  Research Study

• Full title

  Phase II study of cabozantinib in patients with metastatic gastrointestinal stromal tumor (GIST) who progressed during neoadjuvant, adjuvant or palliative therapy with imatinib and sunitinib.

• IRAS ID

  211974

• Contact name

  Charlotte Benson

• Contact email

  charlotte.benson@rmh.nhs.uk

• Sponsor organisation

  European Organisation for Research and Treatment of Cancer (EORTC)

• Eudract number

  2014-000501-13

• Clinicaltrials.gov Identifier

  NCT02216578

• Duration of Study in the UK

  2 years, 9 months, 29 days

• Research summary

  Summary of Research
  The purpose of this study is to find out whether giving the drug cabozantinib to people with metastatic gastrointestinal stromal tumour (GIST) is safe and is working against the disease, after failure of the standard medicines imatinib and sunitinib. For people in this situation there are very limited treatment options currently available.

  Cabozantinib is currently approved in the United States and in Europe to treat people with a rare thyroid cancer and it is currently being studied to treat people with multiple cancer types including GIST. To date more than 2300 people with cancer have been treated with cabozantinib.

  The study will look at the effects of cabozantinib on GIST using clinical examinations, regular scans and blood tests. Tumour samples and blood tests will also be used to understand the effects of the drug. Assessing the activity of cabozantinib in this study will determine whether further exploration of the drug is warranted in metastatic GIST.

  All participants will receive cabozantinib and will continue to take it until they experience no further benefit from the treatment.

  This study will take place in NHS sites in the UK as part of a wider international study. The study is sponsored and co-ordinated by a non-profit organisation called the EORTC (European Organisation for Research and Treatment of Cancer), based in Brussels.

  Summary of Results
  The research team found that cabozantinib could be a useful treatment for GIST that had spread.

  Trial design
  This trial was for people with gastro intestinal stromal tumour (GIST) that had spread. They’d already had treatment with imatinib and sunitinib, but their GIST had continued to grow.

  Everyone taking part had cabozantinib tablets once a day. They took it for as long as it was working and the side effects weren’t too bad.

  Results
  A total of 50 people joined this trial. They all had GIST that had spread.

  At 12 weeks after starting treatment, the research team looked at how many people’s GIST had not grown any more. They found it was 30 out of 50 people (60%).

  They also looked at how well the treatment worked overall. They were able to assess this for 49 out of the 50 people who took part. They found that the cancer:
  - got a bit smaller in 7 people (14%)
  - stayed the same in 34 people (68%)
  - continued to grow in 8 people (16%)

  These results are a bit better than you would expect with other treatments available for GIST that has spread.

  Side effects
  Nearly everyone taking part had at least 1 side effect, but some of these were mild.

  Non serious side effects
  The most common non serious side effects were:
  - 38 people (76%) had diarrhoea
  - 30 people (60%) had sore skin on their hands and feet (palmar plantar syndrome)
  - 25 people (50%) had extreme tiredness (fatigue)
  - 21 people (42%) had increased blood pressure
  - 20 people (40%) had weight loss
  - 15 people (30%) had a sore mouth (mucositis)

  Some people had the same side effects, but they were worse. This included 13 people (26%) who had more severe diarrhoea. And 4 people (8%) who had more severe palmar plantar syndrome.

  Serious side effects
  Researchers can class a side effect as serious for a number of reasons, including if:
  - the person has to go to hospital because of it
  - it is particularly important for the specific treatment in the trial

  A total of 15 people in this trial had a serious side effect.

  The most common serious side effects were:
  - 3 people (6%) had diarrhoea
  - 2 people (4%) had a change in heart rhythm called atrioventricular block
  - 2 people (4%) developed a small tube between the bowel and the skin (an anal fistula)

  Measuring how well treatment works
  In 2022, the research team looked at a new way to measure how well treatment had worked. They used a system that looked at the density of the cancer as well as the size. This is called the Choi criteria.

  They also used the RECIST criteria, which was the standard system used at the time. Someone at each hospital looked at the scans of the people taking part there (local RECIST). And someone at a central hospital looked at all the scans (central RECIST).

  The team compared:
  - the Choi criteria
  - local RECIST
  - central RECIST

  They looked at 43 people who took part in the CaboGIST trial.

  The found that the Choi criteria and the central RECIST both classed:
  - more people’s GIST as having got smaller or stayed the same, and
  - fewer people’s GIST as having got worse
  This is compared to local RECIST.

  Conclusion
  The research team concluded that cabozantinib could be a useful treatment for GIST. This is for people whose GIST has continued to grow despite other treatment. They suggest more trials are done.

  They also concluded that it’s important to include the density of GIST when looking to see how well treatment has worked.

  Other trials of cabozantinib in the future may show different results.

• REC name

  North West - Haydock Research Ethics Committee

• REC reference

  17/NW/0312

• Date of REC Opinion

  16 May 2017

• REC opinion

  Favourable Opinion