A trial using BKM120 with trastuzumab for breast cancer that has spread

This trial is looking at using a new drug called BKM120 with trastuzumab for breast cancer that has spread or is locally advanced. This trial is open to people who have HER2 positive breast cancer.

Some breast cancers have large amounts of a protein called HER2 on the surface of the cells. These cancers are ‘HER2 positive’ and can be treated with a drug called trastuzumab which targets the HER2 protein.

Cells normally divide in an organised way. But in cancer cells, proteins that help to control cell growth can change and make the cells grow more quickly.

BKM120 is a type of biological therapy called a PI3K inhibitor. PI3K is a group of proteins that help cancer cells to grow. Blocking the PI3K proteins may help stop cancer cells from growing.

The researchers think that combining BKM120 with trastuzumab may work better than trastuzumab alone.

The aims of this trial are to find out

How well the combination of BKM120 and trastuzumab works
More about the side effects

Recruitment

Start 01/07/2011

End 31/05/2012

Phase

Phase 1/2

Who can enter

You may be able to enter this trial if you

Have breast cancer that is locally advanced or has spread (metastatic) and is HER2 positive
Have cancer that has come back or continued to grow while having trastuzumab or within 12 months of your last treatment
Have had a small piece of tissue (biopsy) taken from your cancer
Have at least 1 area of cancer that can be measured on a scan
Have a scan that shows your cancer has grown in the last 16 weeks
Have had at least 1 and no more than 4 treatments for HER2 positive breast cancer
Had trastuzumab, trastuzumab DM1 (TDM1) or lapatinib as part of your last treatment
Have had no more than 3 chemotherapy treatments for your breast cancer
Are well enough to be up and about for at least half the day (performance status 0, 1, 2)
Have satisfactory blood test results
Are willing to use reliable contraception while having treatment and for 6 months after if there is any chance you or your partner could become pregnant
Are at least 18 years old

You cannot enter this trial if you

Have had a drug similar to BKM 120 before – your doctor can advise you about this
Are not able to have trastuzumab
Have cancer that has spread to your brain and has not been treated – you may join the trial if have had treatment over 4 weeks ago for cancer that has spread to your spine or brain and it is stable
Have problems with your liver, kidneys or pancreas
Have moderate or severe tingling, numbness or pain in your hands or feet (peripheral neuropathy)
Have or have had a mental health problem such as depression or schizophrenia that could affect you taking part in this trial
Have severe symptoms of anxiety
Have serious heart problems that are not controlled with medication
Have high blood pressure that is not controlled by medication
Have moderate or severe diarrhoea
Have diabetes that is not well controlled
Have any condition where your body cannot properly absorb tablets
Have had a blood cell growth factor such as G-CSF or GM-CSF in the last 2 weeks
Are having steroids or any other medication that dampens down your immune system – you may join the trial if your steroids are applied to the skin (topical), inhaled for breathing disorders such as asthma, or in eye drops (you may be able to join the trial if you are having a low dose of steroids, and have been taking them for at least 2 weeks, following treatment for cancer that had spread to your brain)
Have had chemotherapy or any other anti cancer drugs in the last 4 weeks or 6 weeks for nitrosoureas, monoclonal antibodies (apart from trastuzumab) and mitomycin C, or if you are still having side effects from these treatments
Are taking any other medication that could affect you taking part in this trial
Have had radiotherapy to a large area of your body in the last 4 weeks
Have had radiotherapy to relieve symptoms to a small area of your body in the last 2 weeks
Have had major surgery in the last 2 weeks or are still recovering from major surgery
Had another cancer in the last 5 years apart from non melanoma skin cancer that has been successfully removed by surgery or carcinoma in situ of the cervix that has been removed
Are HIV positive
Are pregnant or breastfeeding

Trial design

This is a phase 1/2 trial. There are 2 parts to this trial. In the first part the researchers found out the maximum dose of BKM120 that they could give safely. This part of the trial is now closed.

The second part of the trial will recruit about 60 people from different countries around the world. Everyone taking part will have BKM120 and trastuzumab.

You have trastuzumab through a drip into a vein. You have it once a week.

BKM120 is a capsule you swallow. You take it once a day with a glass of water, 1 hour after a light breakfast, such as fruit juice, toast and jam. For 2 hours after taking BMK120 you cannot eat or drink. During these 2 hours you are able to drink water.

You can continue to have BKM120 and trastuzumab as long as the side effects are not too bad and your doctor feels the treatment is helping you.

As part of this trial, the researchers are looking for substances in the body that they can measure to help them see how a disease is developing or a treatment is working. These are called biomarkers. To find biomarkers, the trial team will ask your permission to take some extra blood samples and also to pluck some hairs from your head or eyebrows.

The researchers will ask you to fill in a questionnaire before you start treatment, at regular times during treatment and after you finish treatment. It will ask about how you are and if the treatment has affected your moods.

The researchers will also ask your permission to take 2 extra tissue samples and an extra blood sample. You don’t have to agree to the samples if you don’t want to. You can still take part in the main trial.

Hospital visits

You will see the doctor and have some tests before starting treatment. These tests include

A physical examination
Blood tests
Urine test
CT scan or MRI scan
Chest X-ray – if needed
Heart trace – ECG
Heart ultrasound – ECHO

During treatment you see the doctor once a week for a physical examination and blood tests. Every 4 weeks you have a heart trace. Every 8 weeks you have a heart ultrasound and CT scan or MRI scan.

At the end of treatment you see the doctor and have the following tests