A trial looking at 5-ALA and Gliadel wafers as part of treatment for glioblastoma (GALA-5)

Who can enter

You can enter this trial if you

• Have had an MRI scan and your specialist multidisciplinary team (MDT) thinks it is very likely you have a glioblastoma multiforme and that you should have surgery followed by radiotherapy and chemotherapy
• Are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
• Have satisfactory blood test results
• Are willing to use reliable contraception for at least 8 weeks after surgery if there is any chance you or your partner could become pregnant
• Are at least 18 years old

You cannot enter this trial if your situation has not been discussed by a specialist multidisciplinary team (MDT), or if you

• Have a tumour that the MDT thinks could have previously been a low grade tumour, is cancer spread to the brain from somewhere else (a secondary brain tumour), or there is some uncertainty about the type of tumour you have
• Are having any other treatment for your brain tumour (apart from steroids)
• Have had any brain surgery (including a biopsy) or brain radiotherapy
• Can’t have either of the trial treatments for some reason
• Have had any other cancer in the last 5 years apart from carcinoma in situ of the cervix or non melanoma skin cancer that was successfully treated
• Have liver disease, heart disease, an infection, or another serious disease
• Are taking any medication that can make your skin sensitive to the light
• Are HIV positive
• Are pregnant or breastfeeding
• Have passed a mental ability test set by the trial team

Trial design

This is a phase 2 trial that will recruit about 60 people in the UK. It is a pilot study to see if it will be possible to run a larger trial. Everybody taking part in the study will have 5-ALA when they have an operation called a craniotomy to remove their brain tumour.

A few hours before your surgery, you have 5-ALA as a drink. Near the end of the operation, the surgeon will use an ultra violet light on a microscope to look for tumour cells that glow red from the 5-ALA. The surgeon then removes as many of these cells as they safely can.

You only have Gliadel wafers if you have a brain tumour that is fast growing (high grade glioblastoma), and most of the tumour was removed during surgery. So to check the grade, a sample of your tumour will be sent to the laboratory while you are having your operation. At the end of the operation, if your surgeon thinks they have removed most of the tumour and it has been confirmed as high grade, they will put the wafers in. The wafers release carmustine into the area where the tumour was removed. Over time, the wafers dissolve. You will not need further surgery to remove them.

When you have recovered from surgery, you have radiotherapy for up to 6 weeks. During this time, you also take temozolomide tablets.

After this 6 week period, you may have a month without any treatment. Then you can have temozolomide tablets for 5 days each month for up to 6 months. Your doctor will explain exactly how much treatment you need after surgery, depending on how well you are.

The trial team will ask you to fill in a diary each day until you finish temozolomide chemotherapy (or for 8 weeks after surgery if you don’t have chemotherapy). In the diary, you record whether you have taken temozolomide that day and if you are feeling unwell or have any side effects.

As part of the trial, the researchers will ask your permission to take some extra blood samples and to keep a sample of the tissue removed during surgery. They will study these samples to see if genes can affect how well the treatment works. You do not have to give these samples for research if you don’t want to, you can still take part in the trial.

Hospital visits

You will see the doctors and have some tests before you start treatment. The tests include

• Physical examination
• MRI scan
• Blood and urine tests
• Tests to check how well your brain and nervous system are working (your neurological status and mental ability)

The trial team will also ask you to fill out 2 questionnaires asking about your general health and any symptoms you have.

When you have surgery, you are likely to be in hospital for a few days.

When you have recovered from surgery, you go to hospital every day (apart from weekends) for up to 6 weeks to have radiotherapy. The treatment takes a few minutes each time. During this time, you also take temozolomide tablets every day (including weekends).

Taking part in this trial means you have 6 extra hospital visits in the first year and 2 each year after that. You will also have some extra MRI scans. The trial team will give you more information about when you will need to go to hospital and what will happen at each visit.

Side effects

You may find the 5-ALA drink tastes sour and you will have medication to try to stop you feeling sick. If you are sick after drinking the solution, you must let your doctor know as your surgery will have to be delayed.

You must avoid strong light, including sunlight for at least 24 hours after having 5-ALA. Your bed in hospital will be away from the window.

The possible side effects of 5-ALA include

• Feeling sick
• Skin reactions (for example a rash that looks like sunburn)
• A drop in your blood pressure

The possible side effects of Gliadel wafers include

• Swelling of the brain
• Wound infection and problems with wound healing
• Headaches due to increased pressure inside your skull

Your surgeon will tell you much more about what to expect during and after surgery to remove your brain tumour.

The side effects of brain radiotherapy include

• Tiredness (fatigue)
• Hair loss
• Worsening symptoms
• Feeling or being sick
• Skin reaction or soreness

The side effects of temozolomide include

• A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
• Feeling or being sick
• Loss of appetite
• Diarrhoea or constipation