BR14 - Concurrent & Adj. Chemo in non 1p/19q deleted anaplastic glioma

• Research type

  Research Study

• Full title

  Phase III trial on Concurrent and Adjuvant Temozolomide chemotherapy in non-1p/19q deleted anaplastic glioma. The CATNON Intergroup trial.

• IRAS ID

  1036

• Contact name

  Sara Erridge

• Sponsor organisation

  EORTC (European Organisation for Research and Treatment of Cancer)

• Eudract number

  2006-001533-17

• ISRCTN Number

  -

• Clinicaltrials.gov Identifier

  NCT00626990

• Research summary

  Research Summary
  This trial is a follow up other EORTC studies (26981 & 26951) addressing the overall strategy of optimising the treatment of patients newly diagnosed with a type of brain tumour called anaplastic glioma with a particular feature (referred to as ??combined 1p/19q loss?) which can be determined from a sample of the tumour or blood.All patients in the trial will get standard treatment for their brain tumour, which is surgery followed by a course of radiotherapy. The trial investigates the best way to use the drug temozolomide (also known as temodal) in addition to this.The primary objectives of this trial are:?½ To assess whether radiotherapy given with a daily dose (tablet) of a drug called temozolomide (??concurrent temozolomide?) improves overall survival as compared to patients not having daily temozolomide with their radiotherapy.?½ To assess whether temozolomide chemotherapy given for up to a year after radiotherapy (??adjuvant temozolomide?) improves survival as compared to no adjuvant temozolomide After completion of all pre-treatment screening procedures, eligible patients will be randomised immediately after surgery to one of the 4 following treatment groups (??arms?):Arm 1 : Radiotherapy (RT) alone (and further treatment including chemotherapy at progression);Arm 2 : RT & concurrent temozolomide chemotherapy (CT);Arm 3 : RT adjuvant CT for 12 months;Arm 4 : RT & concurrent CT adjuvant CT;Approximately 800 patients will be registered, treated according to their allocated group, and followed-up to see how they respond to treatment in terms of the duration of survival, and also to collect information on any side effects and to observe patient-assessed quality of life.

  Summary of Results
  Final results of the CATNON trial allow a good understanding of the role of temozolomide in the treatment of newly diagnosed grade 3 astrocytoma with an IDH mutation.

  Back in 2005, it was unclear what the role of chemotherapy was in patients with grade 3 astrocytoma, Surgery and radiotherapy were standard of care, but at that time no evidence was available of the value of adding chemotherapy to radiotherapy. After the clinical trial that documented the improved outcome in patients with grade 4 glioma of the addition of temozolomide chemotherapy to radiotherapy, an international consortium consisting of Australian, North-American and European investigators investigated the addition of temozolomide chemotherapy during and after radiotherapy in the so-called CATNON trial. This trial enrolled 751 patients between December 2007 and September 2015. During the conduct of the CATNON trial, it became clear that grade 3 astrocytoma could be separated into tumors with and without an alteration in the DNA, in the IDH gene. Patients with a tumor with an IDH mutation were shown to have a much better outcome and a much better response to treatment, and the assessment of the IDH mutation is today part of the standard diagnostics of brain tumors.

  Earlier reports of the CATNON trial published in 2017 and 2021 showed the value of the giving temozolomide to patients with grade 3 astrocytoma after the end of radiotherapy (called ‘adjuvant’ temozolomide), without a clear benefit effect of temozolomide given during radiotherapy (called ‘concurrent’ temozolomide). Also, the benefit of giving temozolomide appeared to be limited to the patients with a grade 3 astrocytoma with the IDH mutation, but the follow-up period in the group of patients with a tumor with an IDH mutation was really too short to be certain about the lack of benefit of the temozolomide given during radiotherapy. We now have more information obtained by continuing the follow-up of the patients that participated to this study. With more data available, the study shows that only patients with a tumor with an IDH mutation benefit, and only of the 12 4-week cycles of temozolomide given after radiotherapy. No value of temozolomide during radiotherapy emerged from the study results. Also, the study has learned the community a lot about the value of other molecular alterations in the tumors with an IDH mutation and the study is for that reason also a major contribution to the understanding of these tumors.
  

• REC name

  Scotland A: Adults with Incapacity only

• REC reference

  09/MRE00/53

• Date of REC Opinion

  2 Dec 2009

• REC opinion

  Further Information Favourable Opinion