Last year in the UK over 60,000 cancer patients enrolled on clinical trials aimed at improving cancer treatments and making them available to all.
A trial of LDE225 and BKM120 for advanced solid tumours
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
This trial is looking at 2 drugs called LDE225 and BKM120 for advanced cancer. It is for people who have one of the following types of cancer
- Breast cancer that has spread to another part of the body
- Advanced pancreatic cancer that has spread outs
- Stomach cancer or cancer where the stomach meets the food pipe (gastro oesophageal junction cancer)
- Bowel cancer that has spread to another part of the body
- A glioblastoma brain tumour that has come back after treatment
LDE225 and BKM120 are both types of biological therapy.
LDE225 is a cancer growth blocker. It stops signals that cancer cells use to divide and grow.
BKM120 blocks a group of proteins called PI3K. Blocking PI3K proteins may also help to stop cancer cells growing.
The main aims of the trial are to
- Find the highest safe doses of LDE225 and BKM120 that you can have at the same time
- See if having these 2 drugs together can slow down or stop the growth of certain types of cancer
- Learn more about the side effects of this drug combination
Who can enter
You may be able to enter this trial if you
- Have breast cancer or bowel cancer that has spread to another part of your body, advanced pancreatic cancer, stomach cancer or cancer where the stomach meets the food pipe (gastro oesophageal junction cancer) or a glioblastoma brain tumour that has come back after treatment
- Have cancer that has got worse despite having treatment or there are no other
- Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
- Have satisfactory blood test results
- Are able to swallow capsules
- Are at least 18 years old
- Are willing to use 2 forms of reliable contraception during the trial and for 6 months afterwards if you are sexually active and there is any chance you or your partner could become pregnant
You cannot enter this trial if you
- Have had chemotherapy or biological therapy in the last 3 weeks (in the last 6 weeks if you had a drug called mitomycin C a
nitrosoureaor a monoclonal antibody)
- Have had hormone therapy in the last week
- Have already had a drug that targets PI3K or a similar type of drug - your doctor can tell you this
- Have had another experimental drug in the last month (or earlier if there is any chance some of the drug could still be in your body)
- Have taken a growth factor for blood cells such as G-CSF in the last 2 weeks
- Have not recovered from the side effects of earlier treatment unless they are very mild, apart from hair loss, a drop in the number of blood cells or changes to way body organs work
- Are known to be very sensitive to LDE225, BKM120 or similar drugs
- Need to continue to take drugs that affect body substances called cytochrome P (CYP) enzymes
- Take a drug to thin your blood called warfarin – it is important that you don’t stop taking any medication before talking to your doctor
- Have a medical condition that affects your muscles, or take drugs that can cause the breakdown of muscle fibres - the trial team can advise you about this
- Have had mental health problems in the past, or have moderate to severe depression or severe anxiety – doctors use questionnaires to assess this
- Have certain heart problems or take other medication that can affect your heart beat – the trial team can advise you about this
steroidsor other drugs that affect your immune system unless it is a very low dose – steroid inhalers, creams or eye drops are allowed
- Have problems with your
digestive systemthat could affect how you absorb medication
- Are known to be HIV positive
- Have any other serious medical condition that the trial team think could affect you taking part
- Plan to start doing any type of strenuous exercise
- Are pregnant or breastfeeding
As well as the above, if you have a glioblastoma, you must not have had radiotherapy in the last 3 months
Apart from people who have a glioblastoma, you cannot take part in the trial if your cancer has spread to your brain and is causing symptoms. You may be able to take part if this has been treated, it is not causing symptoms and 2 scans show that it has not got any worse for at least 3 months. You must have finished treatment for cancer spread to your brain at least 4 weeks ago (2 weeks for stereotactic radiotherapy) and if you are still taking steroids, this must be a low dose which has not been increased in the last 2 weeks.
This phase 1 trial will recruit about 75 people. Everybody taking part has LDE225 and BKM120. Both drugs are capsules that you swallow once a day.
The first few patients taking part will have low doses of both drugs. If they don’t have any serious side effects, the next few patients will have a higher dose of one drug and then the next few will have a higher dose of the other. And so on, until they find the best doses of both drugs to give together. This is called a dose escalation study.
This part of the trial has now finished. The rest of the people joining the trial will have the highest safe doses of the drugs found in the dose escalation study.
As long as you don’t have any bad side effects, you can carry on having LDE225 and BKM120 for as long as the treatment is helping you.
The trial team will get a sample of your cancer that was removed when you had surgery or a
They will also ask you to have another biopsy after 4 weeks of treatment. But these biopsies are optional. You don’t have to have them if you don’t want to.
During the trial, you give some extra blood samples to see how your body absorbs the drugs and how it gets rid of them. This is called
The researchers will also look at your DNA to see how genetic differences can affect how well the drugs work and the side effects people have.
The trial team will ask you to fill in some questionnaires
- Before you start treatment
- Every 2 weeks for the first 8 weeks
- Once every 4 weeks for the rest of the time you have treatment
- When you finish treatment
The questionnaires will ask about your mood, whether you feel depressed and how anxious you are feeling.
You see the trial team and have some tests before you start treatment. The tests include
- Physical examination
- Blood tests
- CT scan or MRI scan
- Heart trace (
- Heart scan (
echocardiogram) or MUGA scan
You go to hospital 12 times in the first 4 months of treatment. After that, you go once every 4 weeks. You have regular blood tests and a CT or MRI scan every 8 weeks. For some hospital visits, you mustn’t eat or drink anything for 10 hours beforehand.
When you finish treatment, you see the trial team again within 2 weeks. You have a physical examination, blood tests, a heart trace and a CT or MRI scan. You have 1 more hospital visit 6 months later.
As both LDE225 and BKM120 are new drugs, there may be side effects we don’t know about yet.
In other trials, the most common side effects of LDE225 have been
- Taste changes
- Muscle spasms
- Feeling or being sick
- Loss of appetite
- Weight loss
- Tiredness (fatigue)
- Muscle pain or damage to your muscles
- Hair loss
- Kidney damage
- An allergic reaction
The most common side effects of BKM120 have been
- High blood sugar levels
- Skin rash and itching
- Eye problems such as
- Sore mouth
- Feeling weak, tired or sleepy
- Trouble sleeping
- Diarrhoea or constipation
- Tummy (abdominal) pain
- Changes to the way your liver works
- Feeling or being sick
- Loss of appetite
- Inflammation of the lungs
- Mood changes including anxiety and depression
You cannot eat certain fruits (or drink their juices) or take certain herbal medicines while having LDE225 and BKM120. This is because they can interfere with the way the trial drugs work in your body. These fruits include grapefruit and Seville oranges.
How to join a clinical trial
Dr Udai Banerji
Experimental Cancer Medicine Centre (ECMC)