MR1396 - GALA-5: An Evaluation of the Tolerability and Feasibility of combining 5-Amino-Levulinic Acid (5-ALA) with Carmustine Wafers (Gliadel) in the Surgical Management of Primary Glioblastoma.

This Cancer Research UK (CRUK) funded pilot trial is using a very small cohort to look at two treatments for a type of brain tumour called a glioblastoma, the most common form of brain tumour in adults.

Doctors often treat glioblastoma with surgery, followed by radiotherapy and a chemotherapy drug called temozolomide. This is standard treatment, but researchers are looking for ways of improving treatment.

In this trial, the researchers at "CRUK and UCL Cancer Trials Centre" are looking at giving 2 other treatments as well as the standard treatment. The first of these is called 5-ALA or Gliolan. It is a dye that makes brain tumour cells glow red under ultra violet light. During surgery, it can help surgeons to check they are removing as much brain tumour as possible.

The other trial treatment is an implant that the surgeon puts into the space left by removing the brain tumour. The implant is called a Gliadel wafer. It contains the chemotherapy drug carmustine. The aim of this treatment is to kill any tumour cells left after surgery.

Some people may already have 5-ALA and Gliadel wafers as part of their treatment, but this is not currently standard treatment. The aims of this trial are to;

•See if it is safe to have 5-ALA and Gliadel wafers with standard treatment

•Find out if this combination of treatments helps people with glioblastoma

The trial will also be looking at whether patients receiving the combination of the two trial treatments do better than expected as to the control of the tumour and their neurological symptoms, and whether they have a better quality of life.

Date and cause of death are being requested to enable the assessment of patient survival in the GALA-5 trial (the name GALA-5 is derived from the name of the treatment used to treat the tumour, such as Gliadel Gliolan-5). As some patients have become lost to follow up over time, obtaining this information for these patients will ensure that the dataset is as complete as possible. Mortality information is being requested only for patients that have become lost to follow up.

The primary objective of the GALA-5 trial is to establish whether the combined use of 5-ALA and Carmustine wafers is safe and does not compromise a patient from receiving or completing standard chemoRT. The secondary objective of this study is to gather preliminary evidence as to whether the combined use of 5-ALA and Carmustine wafers at surgery has the potential to improve clinical outcome.

August 2018 Update:

"CRUK and UCL Cancer Trials Centre at UCL" have requested to hold the data received for a further 3 years for the following reasons:

1) Although the data has been obtained, and the data sets have been analysed, the need is there to use the results in publications as mentioned in the outputs below

2) As this is a clinical trial, it is a requirement to retain the data for 5 years after the trial completion. The trial completion date has not yet been confirmed but publications have not been created, finalised or published yet.

"Cancer Research UK and UCL Cancer Trials Centre" have confirmed that they are one of 13 Centres funded by Cancer Research UK and as such bears its name. The 13 Centres form a network in order to share professional knowledge and expertise (but not data), and each is hosted by a separate legal entity. For ‘Cancer Research UK and UCL Cancer Trials Centre’ the legal entity is UCL.

Cancer Research UK do not have access to the data being shared under this agreement and other than funding they are not involved in the study, nor will they have any influence on the results or suppress any results.

All organisations party to this agreement must comply with the Data Sharing Framework Contract requirements, including those regarding the use (and purposes of that use) by “Personnel” (as defined within the Data Sharing Framework Contract ie: employees, agents and contractors of the Data Recipient who may have access to that data).

The "Cancer Research UK and UCL Cancer Trials Centre" will provide patient date of birth, NHS number and date of diagnosis of glioblastoma to NHS Digital in order to identify these patients. NHS Digital will return mortality data for the cohort. Data from NHS Digital will be integrated (manually) into the existing anonymised trial dataset in a MACRO database (internally maintained database) by the Trial Coordinator.

This dataset is held at the "Cancer Research UK and UCL Cancer Trials Centre" at UCL. Data will be stored electronically on servers with restricted access. There will be no linkage of the received data to other datasets. No third parties have access to these data. This dataset will be analysed by the trial statistician at the "Cancer Research UK and UCL Cancer Trials Centre" using statistical programme software to produce statistical outputs for publications. The trial statistician is a substantive employee of UCL.

The mortality data obtained from NHS Digital will be used to calculate the overall survival of GALA-5 trial patients otherwise lost to follow-up. The GALA-5 trial dataset was analysed as soon as data was received (in August 2016) and researchers will submit the trial results for publication in a peer reviewed journal once they have been finalised.

The manuscript will most likely be submitted to the Journal of Neuro-Oncology. Once the manuscript has been accepted for publication, the results will also be entered on the clinicaltrials.gov database, the EU Clinical Trial Register, and potentially NICE. No record level data will be disseminated. The publication will also be forwarded to Cancer Research UK, who will produce a lay summary that will be uploaded on to the CRUK website. End of the trial reports for the GALA-5 trial have been submitted to the Research Ethics Committee (REC) and The Medicines and Healthcare products Regulatory Agency (MHRA), which summarised the main findings. Submitting these requirements within 12 months of end of trial being declared was a requirement. No further report will be required by the MHRA.

Survival data of individual patients will not be published, no individuals will be identifiable from any publications, nor will record level data be shared with third parties. All published data will be aggregated with small number suppression in line with the HES analysis guide.

The aim of GALA-5 was to establish whether the combined use of 5-ALA and Carmustine wafers during surgery in patients diagnosed with Glioblastoma (GBM) is safe and does not compromise delivery of standard chemo radiotherapy. The results of the GALA-5 trial are also expected to guide the protocol for a new phase III trial that will further explore the use of 5-ALA and Carmustine wafers during surgery in patients diagnosed with Glioblastoma (GBM). This trial will also be run by the "Cancer Research UK and UCL Cancer Trials Centre". The data provided will inform the clinical impact of combination therapy incorporating Carmustine wafers with Temozolomide by providing additional information regarding the cause of death in patients given this combination. The data will also inform reappraisal of NICE TA121 (Carmustine implants and temozolomide for the treatment of newly diagnosed high-grade glioma).

While the NICE TA121 guidelines comment on the use of carmustine wafers and temozolomide, they do not comment on the combined use of carmustine wafers and temozolomide, and are based on historical studies that antedate temozolomide and 5-ALA. By treating patients with both 5-ALA, carmustine and temozolomide, GALA-5 will therefore inform reappraisal of NICE TA121 (and hence patient treatment). Results will be disseminated to NICE by forwarding the final publication. No record level data will be disseminated to NICE.

As per Clinical Trial Regulations, all trial related documentation, including, trial data must be retained for a minimum of 5 years following the end of trial declaration. The end of the trial has not been declared yet. The datasets have been analysed, however, the manuscripts for publication are still being prepared - so no benefits have been yielded from any publications as none have been created yet.