Updating a major clinical trial

Fast facts

• Official title: Identifying 1p/19q intact anaplastic glioma patients benefitting from adding temozolomide to radiotherapy
• Lead researcher: Professor Martin van den Bent
• Where: Erasmus Medical Centre, Netherlands
• When: October 2018 – September 2021
• Cost: £314,725 over a 3 year period
• Research keywords: Adult, Anaplastic Glioma, Grade III, High Grade, Quality of life, Clinical / Academic
• Grant round: Clinical biomarkers
  

---

What is the purpose of this project?

This grant will enable new analysis of an ongoing international clinical trial, which will impact on the future of clinical trials for people diagnosed with anaplastic glioma.

When the CATNON trial started in 2005, the latest scientific thinking showed that people with an anaplastic (Grade III) glioma had a poorer outcome if they had ’intact 1p/19q’. Based on this knowledge, CATNON was designed to test if the addition of chemotherapy (temozolomide) improved outcomes compared to radiotherapy alone.

While this trial has been underway in Europe, the UK, Australia, the USA and Canada, more has been discovered about the genetic traits of brain tumours. Subsequently, the World Health Organisation (WHO) updated the brain tumour classification system in 2016. A key change in this update was the effect of changes in a gene called IDH. If the anaplastic glioma has a change in IDH (known as an IDH mutation), the tumour tends to be less aggressive. But if the IDH is unchanged (known as IDH wildtype), the tumour may have traits of a more aggressive tumour.

The people enrolled on the CATNON trial have a mix of IDH mutant and IDH wildtype tumours. This means that the results of the trial could be confused and unclear because researchers don’t know which IDH types are present. Our funding will allow about 600 tests (next-generation sequencing) to find out which participants have which type of IDH in their tumour.

Once they’ve done the sequencing tests, the researchers will reanalyse the CATNON outcome data they’ve gathered so far. They will aim to see if the temozolomide treatment works better against tumours with or without the IDH mutation, so that future treatments are more effective, and kinder.

Project objectives:

1. To better understand the effects of abnormal genes on outcome.
2. To identify the patients that really benefit from adding chemotherapy to radiotherapy.
3. Identify groups of patients in which other targeted drugs may be effective.

Why is it important?

This research project will play an important role by informing the prognosis for people with anaplastic gliomas. It will also help tailor treatments by identifying which people would benefit from more or less intense treatment and improve quality of survival.

The state-of-the-art molecular analysis of the largest phase III clinical trial ever conducted on anaplastic glioma will allow analysis of IDH mutations according to the WHO classification 2016, which is the tool that’s now used for diagnosis for patients with this disease. It will ensure that patients diagnosed today and tomorrow will get the maximum benefit from this important trial. Depending on identified prognostic factors, we hope the project will identify which anaplastic glioma patients need less or more aggressive treatment.

Who will it help?

This study will add value and impact to the results of this trial, which over 750 people with brain tumours have contributed to so far.

The learnings from the trial will help shape the future standard of care for people diagnosed with types of anaplastic glioma, as well as the clinical trials that will build on the knowledge from this one.

The people identified as needing less treatment will benefit from improved quality of life.

Those that survive longer because of this research will be able to share that time with their friends and families.

Optimal treatment starts with a reliable diagnosis. This project will allow a better diagnosis with better prognostication of individual patients resulting in better guidance on treatment selection

Professor Martin van den Bent

Milestones

Achieved

• All available tumour samples have been analysed to find out if the tumour contains the normal or mutant (altered) version of IDH.
• Results from the re-analysis of the CATNON trial have highlighted that patients who have mutations in IDH have improved survival when chemotherapy is given after radiotherapy. This was not seen in patients who do not have IDH mutations.
• The researchers have discovered that different types of IDH mutations are associated with differences in tumour aggressiveness

Upcoming

Continue to explore how the different IDH mutations affect how aggressive the tumours are and highlight if these could serve a prognostic role. This could lead to a more personalised treatment programme being offered to patients based on their IDH status