A trial of BKM120 with paclitaxel for advanced HER2 negative breast cancer (BELLE 4)

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

Cancer type:

Breast cancer




Phase 2/3

This trial is looking at a drug called BKM120 with paclitaxel for breast cancer that is HER2 negative and has spread into tissue surrounding the breast or to another part of your body.

If breast cancer has spread outside the breast, doctors may use chemotherapy or biological therapy to treat it.

Breast cancer cells often have receptors for a protein called HER2. If there are only small numbers of these receptors, the cancer is called HER2 negative.

HER2 negative breast cancer is unlikely to respond to drugs such as the biological therapy drug Herceptin and researchers are looking for new treatments to help women who have this type of breast cancer.

In this trial, they are looking at a drug called BKM120 alongside a chemotherapy drug called paclitaxel that doctors already use to treat breast cancer. BKM120 is a type of biological therapy.  It is a cancer growth blocker.

The women taking part in this trial have breast cancer that is HER2 negative and has spread into surrounding tissue or to another part of the body. The aim is to see if paclitaxel and BKM120 is better than paclitaxel alone for this group of women.

Who can enter

You may be able to enter this trial if

  • You are a woman with breast cancer that has spread into tissue surrounding your breast (locally advanced) and can’t be removed with surgery, or has spread to another part of your body
  • Your cancer is HER2 negative
  • Your doctors are able to measure your cancer
  • You are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
  • You are able to swallow medication
  • You have satisfactory blood test results
  • You are at least 18 years old
  • You are willing to use reliable contraception during the trial and for at least 4 weeks afterwards if there is any chance you could become pregnant

As well as the above, the trial team need to get a sample of your tumour to look for changes in the cells. If they can get a sample of tissue that was removed when you had surgery or a biopsy Open a glossary item in the past they will test this. But if there isn’t a sample available, they will ask you to have a new biopsy. You can’t take part in the trial if the team can’t get a sample of your breast cancer.

You cannot enter this trial if you

  • Have already had chemotherapy for breast cancer that has spread outside your breast, or chemotherapy before or after surgery to remove breast cancer if the cancer came back or spread to another part of your body during treatment or within 6 months of finishing it (within 12 months if you had a taxane drug Open a glossary item)
  • Have cancer that has spread to your brain or spinal cord and is causing symptoms – you can take part if cancer spread to your brain was treated at least 4 weeks ago, is not causing symptoms and you are no longer taking steroids
  • Have already had a drug that targets a protein called PI3K or AKT – your doctor can advise you about this
  • Have had surgery in the last 2 weeks, or have not fully recovered from earlier surgery
  • Have had radiotherapy in the last 4 weeks (in the last 2 weeks if it was radiotherapy for symptoms given only to a small area of your body)
  • Haven’t fully recovered from the side effects of earlier radiotherapy treatment
  • Have had any other cancer in the last 3 years apart from non melanoma skin cancer or cervical cancer that was successfully treated
  • Have had growth factors called G-CSF or GM-CSF in the last 2 weeks
  • Take steroids Open a glossary item or any other medication that can damp down your immune system (steroid creams, eye drops and inhalers are allowed)
  • Take warfarin (or a similar drug) to thin your blood
  • Take medication that can affect body substances called cytochrome P (CYP) enzymes – it is important that you don’t stop any medication without talking to your doctor
  • Have had mental health problems in the past, or have moderate to severe depression or severe anxiety – doctors use questionnaires to assess this
  • Have had a heart attack in the last 6 months, have certain other heart problems, or take medication that can affect your heart – the trial doctors can advise you about this
  • Have problems with your digestive system Open a glossary item that could affect how you absorb drugs
  • Are known to be very sensitive to paclitaxel or drugs made in a similar way
  • Can’t take steroids or other drugs to prevent a reaction to paclitaxel
  • Have any other medical condition that the trial team think could affect you taking part
  • Are known to be HIV positive
  • Are pregnant of breastfeeding

Trial design

This phase 2/3 trial will recruit more than 500 women around the world. It is a randomised trial. The women 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. This is called a double blind trial.

  • Women in group 1 have paclitaxel and BKM120
  • Women in group 2 have paclitaxel and a dummy drug (placebo Open a glossary item)

BELLE 4 trial diagram

You have paclitaxel through a drip into a vein once a week. It takes an hour each time. BKM120 and the dummy drug are capsules that you swallow once a day.

As long as you don’t have bad side effects, you can carry on having the trial treatment for as long as it helps you.

The researchers will ask you to fill in some questionnaires

  • Before you start treatment
  • 3 times in the first 8 weeks of treatment
  • Once every 4 weeks after that
  • When you finish treatment

Some of the questionnaires will ask about your mood and whether you feel depressed. Others will ask how anxious you are feeling.

In the first 100 women to join the trial, the researchers will take a number of extra blood samples to learn more about what happens to the drugs in your body. This is called pharmacokinetics Open a glossary item. If you have these extra blood tests, some of your hospital visits will be longer. The trial team will explain this to you.

Hospital visits

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

  • Physical examination
  • Blood tests
  • Urine tests
  • Heart trace (ECG Open a glossary item)
  • Heart scan (an echocardiogram Open a glossary item) or MUGA scan Open a glossary item
  • CT scan or MRI scan

If you have any cancer on your skin, your trial doctor may take a photograph. This will only show the cancer and the surrounding area. Your face will not be in the photograph and it will not be possible to identify you.

During treatment, you go to hospital for treatment once a week. You see your trial doctor once every 4 weeks. You also have

  • Regular blood tests
  • A heart trace every 4 weeks
  • A CT or MRI scan every 8 weeks
  • A heart scan every 4 months

When you finish treatment, you see the trial team within the next week. You have a physical examination, blood tests, a heart trace and a heart scan. You may also have a CT or MRI scan and an X-ray. The trial team will then contact you once every 3 months to see how you are.

If you stop the trial treatment because your cancer has started to get worse, the trial team may ask you to have another biopsy. This will help them to learn more about how breast cancer responds to BKM120 and why it stops responding to the treatment. But you don’t have to have this biopsy if you don’t want to.

If you stop the trial treatment for any reason other than your cancer getting worse, you have a CT or MRI scan every 8 weeks. This will continue until your cancer starts to get worse or you start another treatment. After that, the trial team will contact you every 3 months to see how you are getting on.

Side effects

BKM120 is a new drug so there may be side effects we don’t know about yet. The most common known side effects include

The side effects of paclitaxel include

  • A drop in blood cells causing an increased risk of infection, tiredness and breathlessness
  • Diarrhoea or stomach upset
  • Hair loss
  • Joint and muscle pain
  • Numbness and tingling in your hands and feet (peripheral neuropathy)
  • Change to your heart rate or a drop in your blood pressure
  • Sore mouth or lips
  • Irritation where you have the injection

Paclitaxel can cause an allergic reaction. To try to stop this happening, you have other drugs before the paclitaxel drip.

We have more information about the side effects of paclitaxel in our cancer drugs section.

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Iain MacPherson

Supported by

Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

Oracle 9854

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Harriet wanted to try new treatments

A picture of Harriet

“I was keen to go on a clinical trial. I wanted to try new cancer treatments and hopefully help future generations.”

Last reviewed:

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