A trial of AZD4547 with exemestane for breast cancer that is oestrogen receptor positive and has extra copies of a gene called FGFR1

You may be able to enter the first part of this trial if you

• Are a woman or man with breast cancer that is oestrogen receptor positive
• Have at least 1 area of cancer that doctors can see on a scan or X-ray
• Have had 1 other type of hormone therapy after surgery to remove breast cancer (adjuvant therapy) and your cancer got worse during this treatment or within a year of finishing it, or you have had 1 type of hormone therapy for breast cancer that has spread into surrounding tissue or to another part of the body (advanced breast cancer) and your cancer has got worse despite this – you can take part if you had 1 type of adjuvant hormone therapy in the past as well as 1 type of hormone therapy for advanced cancer
• Have been through the menopause (if you are a woman)
• 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 over 25 years old

You may be able to enter the second part of this trial if the points above apply to you and

• The trial doctors can see from a sample of your cancer that it contains extra copies of the FGFR1 gene
• The area of cancer that doctors can see on a scan is at least 10mm in size and has not been treated with radiotherapy

You cannot enter this trial if you

• Have cancer that has spread to your brain or spinal cord unless it has been treated, is not causing symptoms or getting worse and you have not needed to take steroids in the last 4 weeks
• Have had more than 1 type of chemotherapy for advanced breast cancer – you may have also had chemotherapy after surgery for breast cancer to try to stop the cancer coming back (adjuvant therapy) but people joining the second part of the trial can have only had adjuvant therapy – you cannot join the second part of the trial if you have had chemotherapy for advanced breast cancer
• Have had more than 1 other type of hormone therapy for advanced breast cancer (you can take part if you have also had surgery to remove your ovaries or drugs called LHRH blockers to stop your ovaries working)
• Have already had exemestane or drugs that block FGF receptors
• Have had major surgery in the last 4 weeks
• Have had radiotherapy to a large area of your body in the last 4 weeks or radiotherapy for symptoms in the last 2 weeks
• Have not recovered from the side effects of other cancer treatment (apart from hair loss) unless they are very mild
• Take drugs that affect enzymes such as CYP3A4 in the 2 weeks before starting the trial treatment – the trial doctors can advise you about this
• Take St John’s wort in the 3 weeks before starting the trial treatment
• Have had any other cancer in the last 5 years apart from non melanoma skin cancer or carcinoma in situ of the cervix that have been successfully treated
• Have sickness that cannot be controlled with medication or any other problems that mean you would be unable to swallow or absorb tablets
• Are known to be very sensitive to anything in the trial drug or exemestane
• Have high blood pressure that cannot be controlled with medication or heart problems that are a cause for concern
• Have active infections such as hepatitis B, hepatitis C or HIV, or any other serious medical condition that the trial team think could affect you taking part

This phase 2 trial will recruit about 72 people all together in a number of different countries.

The first part of the trial will recruit about 12 people with oestrogen receptor positive breast cancer. They will all have exemestane and AZD4547. The first patients taking part will have a low dose of AZD4547. If they don’t have any serious side effects, the next patients will have a higher dose. And so on, until they find the best dose to give alongside exemestane. This is called a dose escalation study.

The second part of the trial will recruit about 60 people who have oestrogen receptor positive breast cancer that also has extra copies of the FGFR1 gene - the trial doctors will get a sample of tissue that was removed when you had surgery or a biopsy to check for this.

This part of the trial is randomised. The people taking part are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in. And neither of you will know which group you are in either. This is called a double blind trial.

Half the people taking part have the highest safe dose of AZD4547 that was found in part 1of the trial alongside exemestane. The other half will have a dummy drug (placebo) alongside exemestane.

You take AZD4547 (or the dummy drug) as tablets twice a day. You take exemestane tablets once a day. As long as you don’t have bad side effects, you can carry on having the treatment for as long as it helps you.

If your cancer gets worse during treatment, the doctors can find out which group you are in. If you have been taking the dummy drug, they may talk to you about switching over to taking AZD4547. This is called an extension study.

During the trial, the researchers will take some extra blood samples. They will use some samples to learn more about what happens to the drugs in your body. This is called pharmacokinetics. They will also take samples to look for substances called biomarkers that are able to show how the treatment is affecting you. They hope that this research will help doctors in the future to work out who is most likely to benefit from the study drug. They may talk to you about having extra biopsies to look for biomarkers.

The trial team may also ask your permission to take another blood sample to study your DNA. They want to learn more about how genes can affect the way people respond to this treatment. This is optional. If you don’t want to give this sample for research, you don’t have to. You can still take part in the trial.

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

• Physical examination
• Eye tests
• Heart trace (ECG)
• Blood and urine tests
• Heart ultrasound (echocardiogram) or MUGA scan
• CT scan, MRI scan or X-ray

People joining the first part of the trial begin by taking exemestane on its own for 7 days. You go to hospital on the 1st day and the 7th day. Then you start having both exemestane and AZD4547 in 3 week cycles of treatment.

People joining the second part of the trial have both drugs in 3 week cycles of treatment from the start.

Everybody taking part goes to hospital 3 times in the first cycle of treatment and at least once in every cycle after that. You have regular blood tests and a number of ECGs.

In the 2nd cycle of treatment, you have another eye test and an echocardiogram or MUGA scan. You have a CT scan, MRI scan or X-ray every 12 weeks.

After you finish the treatment, you go back to see the trial team a month later.

As AZD4547 is a new drug, there may be some side effects we don’t know about yet. The possible side effects include

• Dryness of the eyes, mouth and skin
• Changes to your eyes which may affect your vision – it is important that you tell the trial doctors if you notice any change in your vision
• Increases in the levels of phosphates and calcium in your blood
• Sore mouth
• Feeling or being sick
• Diarrhoea or constipation
• Reduced appetite
• Tiredness (fatigue)
• Tingling sensation in your hands and feet (peripheral neuropathy)
• Changes to your nails
• Hair loss

There is more information about the side effects of exemestane on CancerHelp UK.