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

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Breast cancer

Status:

Closed

Phase:

Phase 2

This trial is looking at a drug called AZD4547 with hormone therapy for breast cancer that is oestrogen receptor positive Open a glossary item . Your cancer must also contain extra copies of a gene called FGFR1 and have got worse despite having another type of hormone therapy.

If your breast cancer cells have oestrogen receptors, the cancer is said to be ER positive. Doctors can treat ER positive breast cancer with hormone therapy. One hormone therapy drug they may use is exemestane, another is fulvestrant.

In this trial, researchers are looking at a new drug called AZD4547 alongside hormone therapy. AZD4547 is a type of biological therapy. It blocks the action of a growth factor called fibroblast growth factor (FGF).

Growth factors are natural body chemicals that control cell growth. They work by binding to receptors on cancer cells. This sends a signal to the inside of the cell, which sets off a chain of chemical reactions.

If there are extra copies of a gene called FGFR1 in breast cancer cells, the cells have a large number of FGF receptors. As AZD4547 blocks these receptors, it may stop the cancer growing.

The trial is in 2 parts. In the first part, the researchers are looking for the highest dose of AZD4547 that you can have at the same time as hormone therapy. The people joining this part of the trial have AZD4547 alongside exemestane.

In the second part of the trial they want to see if the highest safe dose of AZD4547 and hormone therapy helps people who have breast cancer with extra copies of the FGFR1 gene. People joining this part of the trial have AZD4547 alongside fulvestrant.

Who can enter

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 already had exemestane or fulvestrant (depending on which part of the trial you join) 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

Trial design

This is a phase 2 trial. The first part of the trial is recruiting about 12 people with oestrogen receptor positive breast cancer. They 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 90 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 Open a glossary item 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 1 of the trial alongside fulvestrant. The other half will have a dummy drug (placebo Open a glossary item ) alongside fulvestrant.

You take AZD4547 (or the dummy drug) as tablets twice a day. You have fulvestrant as an injection into a muscle. You have injections every 2 weeks for the first 3 doses and then every 4 weeks after that. 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 Open a glossary item . 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 Open a glossary item 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.

Hospital visits

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

You go to hospital once a week for the first 4 weeks, then every 2 or 3 weeks for the next couple of months and once a month for the following 3 months. The trial team will let you know how often you need to go to hospital after that.

You have regular blood tests and a number of ECGs, MUGA scans and CT scans. You have an eye test once a month for the first 3 months, then once every 2 months for the rest of the time you are having treatment.

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

Side effects

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