A trial of AZD0424 for advanced solid tumours

You may be able to enter this trial if you

• Have a solid tumour that has continued to grow despite all other available treatments or you have a cancer for which there is no standard treatment
• Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
• Have satisfactory blood test results
• Are at least 18 years old
• Are willing to use reliable contraception during the trial and for 6 months afterwards if there is any chance that you or your partner could become pregnant

If you join the trial when researchers are giving people the highest dose being looked at in this trial, you must have an area of cancer that they can safely take a tissue sample (biopsy) from, or be able to have a PET scan. You must agree to have the biopsy or PET scan in order to enter this part of the trial.

You cannot enter this trial if you

• Have cancer that has spread to your brain, unless this was treated at least 3 months ago, has not got worse since then and is not causing symptoms
• Have had radiotherapy (apart from radiotherapy for symptoms) in the last 4 weeks
• Have had chemotherapy, hormone therapy or immunotherapy in the last 4 weeks (6 weeks if you had chemotherapy drugs called nitrosureas or mitomycin)
• Have not recovered from the side effects of other treatments (apart from hair loss) unless they are very mild
• Have not yet recovered from major surgery to your chest or tummy (abdomen)
• Have a lung condition called interstitial lung disease
• Have an autoimmune disease
• Have low blood pressure or certain heart problems – the trial doctors can advise you about this
• Have an infection that cannot be controlled with medication or any other serious medical condition that the trial doctors think could affect you taking part
• Are taking part in a clinical trial looking at another experimental treatment
• Are known to be HIV, hepatitis B or hepatitis C positive
• Are allergic to peanuts
• Are pregnant or breastfeeding

This is a phase 1 trial. Everybody taking part will have AZD0424.

The first few patients will have a low dose of AZD0424. If they don’t have any serious side effects, the next few patients will have a higher dose. And so on, until the researchers find the best dose to give. This is called a dose escalation study.

Once the researchers have found the highest dose of AZD0424 that at least 6 people had safely, they will give this dose to 12 more people to learn more about the effect the drug has on the body.

You take AZD0424 capsules each day. You must not eat, or drink anything apart from water, for 3 hours beforehand and 1 hour afterwards.

You can carry on taking AZD0424 for as long as the trial doctors think it is helping you.

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

• Physical examination
• Blood tests and urine tests
• Heart trace (ECG)
• Heart ultrasound (echocardiogram) or MUGA scan
• CT scan or MRI scan (if you haven’t had one in the last 4 weeks)
• A special CT scan that takes very detailed pictures of your lungs (lung high resolution computerised tomography or HRCT)

If you are 1 of the 12 people who join the trial when researchers are giving people the highest dose of AZD0424, you will also have 1 of the following

• 6 people have a biopsy before the first dose of AZD4024 and another one after 4 weeks of treatment - the researchers will use these samples to see how the drug affects their cancer
• 6 people have a PET scan before they start treatment and again 2 weeks after the first dose of AZD0424

You go to hospital to have your first dose of AZD0424. You must not eat anything from the night before. You go back for blood tests on the following 2 days.

You then take the capsules at home, but you go to hospital once a week for first 4 months of treatment. If everything is going well after the first 4 months, your hospital visits change to once every 2 weeks.

Throughout your treatment, you have regular blood tests. And you have a CT or MRI scan every 8 weeks.

When you finish treatment, you go back and see the trial team 4 weeks later.  You have a physical examination, blood tests, urine tests, a heart trace and a CT scan. If you are having side effects, the trial team will continue to see you until these get better, or until you start another treatment.

As AZD0424 is a new drug, there may be side effects we don’t know about yet. Possible side effects include

• Diarrhoea
• Feeling or being sick
• A drop in your blood pressure
• Changes to your heart or your liver
• Dizziness
• Tiredness (fatigue)
• Skin rash
• A drop in some types of blood cells causing an increased risk of infection and bleeding problems

If you have biopsies, you will have a local anaesthetic beforehand, but it may be a bit painful or uncomfortable afterwards. The after effects will depend on where in the body you have the sample taken from. There may be a small amount of bleeding and you may need to have some stitches. You have these removed after a few days.