A trial looking at different drug combinations for breast cancer
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer type:
Status:
Phase:
This trial is looking at different combinations of drugs called LEE011, BKM120 and BYL719 alongside the hormone therapy drug fulvestrant. It is for women with breast cancer that has grown into surrounding tissue or spread to another part of the body. Their breast cancer must have receptors for the female hormones oestrogen or progesterone.
If breast cancer has hormone receptors, doctors can treat it with hormone therapy. One type of hormone therapy is fulvestrant. Researchers want to find out if giving other drugs with hormone therapy can improve treatment.
More about this trial
In this trial, researchers are looking at 3 drugs called LEE011, BKM120 and BYL719. They are all types of biological therapy called cancer growth blockers. They stop signals that cancer cells use to divide and grow.
Women in this trial will have one of the following drug combinations
- LEE011, BKM120 and fulvestrant
- LEE011, BYL719 and fulvestrant
- LEE011 and fulvestrant
There are 2 different parts to the trial. The first part aims to find the best doses of LEE011, BKM120 and BYL719. In the second part, researchers want to find out which combination of treatment is best at treating breast cancer.
Who can enter
You may be able to join this trial if all of the following apply
- You have breast cancer that has grown into surrounding tissue or spread to another part of your body and you can’t have surgery or radiotherapy to cure your cancer
- Your breast cancer is sensitive to the females hormones oestrogen or progesterone
- The trial team can do some tests on a sample of tissue that was removed when you had your breast cancer surgery. If a sample of tissue is not available, you must be willing to have a new sample taken
- You are a woman who has been through the menopause (
postmenopausal) 
- Your cancer has come back or continued to grow while taking a drug called an aromatase inhibitor (AI) such as exemestane, anastrozole or letrozole
- You have satisfactory blood test results
- You are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
- You are a woman and are at least 18 years old
- You have cancer that can be measured on a scan, you may also be able to take part if you have certain types of secondary bone cancer that are visible on a scan but cannot be measured (the trial team can explain this to you in more detail)
You cannot join this trial if any of these apply. You
- Have breast cancer that has a large number of HER2 receptors (
HER2 positive cancer) - Have cancer that has spread to your brain and is causing you symptoms. You can take part if you have recovered from any treatment for your cancer spread to your brain, you do not need medicine to prevent you from having a fit and if you take steroids, the dose has been the same for at least 2 weeks
- Have had more than 2 types of chemotherapy to treat breast cancer that has come back or spread. If you join the second part of the trial, you can only have had 1 type of chemotherapy for cancer that has spread
- Have had chemotherapy in the last 2 weeks (or in the last 6 weeks if you had a drug called mitomycin C, or a drug belonging to group of chemotherapy drugs called
nitrosoureas ) - Have had radiotherapy or major surgery in the last 2 weeks
- Have had biological therapy in the last 2 weeks
- Have had hormone therapy in the last 2 weeks. If you are currently taking fulvestrant, you don’t need to stop treatment but you may need to delay your next dose (the trial team will give you more information about this)
- Have already had drugs that blocks the action of certain proteins called CDK or P13K. You may be able to take part if you had this type of drug in an early phase trial (the trial team can advise you more)
- Are still having side effects from any anti cancer treatment, apart from hair loss
- Have had any other cancer in the last 3 years apart from carcinoma in situ of the cervix or non melanoma skin cancer that was successfully treated. You may be able to take part if you have another type cancer that is not growing and is not causing any symptoms (the trial team can give you more detail about this)
- Have taken any medication that affects body substances called CYP enzymes in the last 5 days (your doctor can advise you about this)
- Have already had drugs that blocks the action of certain proteins called CDK or P13K. You may be able to take part if you had this type of drug in an early phase trial (the trial team can advise you more)
- Are taking any medicine that damps down the
immune system (immunosuppressants) - Have problems with high blood pressure (hypertension)
- Have certain heart problems (the trial team can advise you about this)
- Have any other serious medical condition or mental health problem that the trial team think could affect you taking part
- Are allergic to the drugs used in this trial
- Are taking part in another trial looking at a cancer treatment
Trial design
This trial has 2 different parts. The researchers need 36 people to join the first part from different hospitals across the world.
If you join the first part, you have one of the following combinations of treatment
- LEE011, BKM120 and fulvestrant
- LEE011, BYL719 and fulvestrant
- LEE011 and fulvestrant
Which treatment you have and which dose of LEE011, BKM120 or BYL719 you have will depend on when you join the trial. Everyone has the same standard dose of fulvestrant.
The first few patients taking part will have a low dose of LEE011. They will be monitored by the trial team for 1 month. If they don’t have any serious side effects, they will also have the lowest dose of BKM120 or BYL719 (depending on which group they are in).
If they don’t have any serious side effects the next few patients will have a higher dose of BKM120 or BYL719. And so on, until they find the best dose to give. This is called a dose escalation study.
The researchers need 180 to join the second part of the trial. This part is randomised. The people taking part are put into treatment groups by computer. Neither you nor your doctor will be able to decide which group you are in. But you will know which treatment you are going to have. The possible treatments are
- LEE011, BKM120 and fulvestrant
- LEE011, BYL719 and fulvestrant
- LEE011 and fulvestrant
You have the best dose of LEE011, BKM120 and BYL719 found in the first part of the trial.
Whichever part of the trial you join, you have BKM120 as capsules once a day for 4 weeks. You have BYL719 as tablets once a day for 4 weeks. You have LEE01 as capsules once a day for 3 weeks, then a week without treatment.
Some people in both the first and second part of the trial will be asked to take LEE011 during this 7 day period as well (the trial team will discuss this with you in more detail if this applies to you). Each 4 week period is called a cycle of treatment
You have fulvestrant as 2 injections, one into each buttock. You have these injections on the 1st and 15th day of your first cycle of treatment, then only on the first day of each cycle after that.
You have treatment for as long as it is helping you and as long as you don’t have any serious side effects.
The researchers will ask your permission to take 2 samples (biopsies) of your cancer before treatment and about 1 month after starting treatment. This is in addition to the tumour sample needed to be able to take part in the trial.
The researchers will use these samples to look at genes and proteins to find out if these relate to how treatment works and why some cancers become to treatment. You don’t have to agree to have these biopsies if you don’t want to. You can still take part in the trial.
Hospital visits
You will see the doctors and have some tests before you start treatment. The tests include
- Blood tests
- Physical examination
- Heart trace (
ECG ) - Heart scan (
echocardiogram ) or MUGA scan - CT scan or MRI scan
- Bone scan
The trial team may ask you to complete 2 questionnaires to assess your mood. This is because BKM120 is known to alter mood in some people. If you have (or have had) a psychiatric problem in the past or you have had problems with depression, the trial doctor may decide that it would not be advisable for you to take part in this trial.
Once you have started treatment you visit hospital
- 4 times during the first (4 week) cycle
- Twice during the 2nd cycle
- Every 4 weeks after that
At these visits you see a doctor who will ask you about side effects and you have some blood tests. On the appointment days you will be asked not to eat any food for 8 hours before going to hospital (you can drink water) and to take your drugs at hospital rather than at home.
You have an ECG six times over the first 2 months, then a heart scan or MUGA scan every 4 months. You have further CT or MRI scans 1 month after the start of treatment and about every 3 months after that.
If you are taking BKM120, you may be asked to complete further questionnaires to assess your mood at some of your appointments.
Once you have finished treatment, you visit hospital 2 weeks later to see a doctor and have some blood tests. You may also have some of the above tests.
A member of the trial team will contact you 1 month after the end of the treatment to ask how you are. If you have any side effects, the trial team will continue to contact you and offer advice as long as these side effects are a problem.
Side effects
The most common side effects of LEE011 include
- A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
- Feeling or being sick
- Diarrhoea
- Tiredness (fatigue)
- Changes to the way your kidneys and heart works
The most common side effects of BKM120 include
- Feeling or being sick
- Diarrhoea
- Loss of appetite and taste changes
- High blood sugar levels
- Tiredness (fatigue) and difficulty sleeping
- Skin rash
- Sore mouth
- Changes to how your liver works
- Dizziness
- Anxiety or depression
- Mood changes
- Headache
- Cough
- Joint pain or back pain
- Swelling of hands and legs
- Shortness of breath or difficulty breathing
- A drop in while blood cells causing an increased risk of infection
- Changes to the way your pancreas works (the trial team will test for this)
The most common side effects of BYL719 include
- High levels of sugar in the blood
- Feeling or being sick
- Diarrhoea
- Loss of appetite and taste changes
- Weight loss
- Stomach pain
- Sore mouth
- Tiredness
- Skin rash, redness of skin with or without itching
- Dry skin
The most common side effects of fulvestrant include
- Pain or swelling where you have the injections
- Changes to how your liver works
- Feeling or being sick
- Tiredness (fatigue)
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.
Chief Investigator
Dr Samreen Ahmed
Supported by
Experimental Cancer Medicine Centre (ECMC)
Novartis
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
