“I think it’s really important that people keep signing up to these type of trials to push research forward.”
A trial of entrectinib for advanced solid tumours (STARTRK-2)
This trial is mainly for people with a solid tumour that has grown into surrounding tissues (is locally advanced) or spread to another part of the body (metastatic).
More about this trial
Cells normally grow in a very orderly way. Chemical messages or signals tell them when to grow and when to die. Changes to genes in cancer cells can signal them to grow abnormally or the cell doesn’t die as it should.
Researchers want to improve treatment for people with advanced cancer whose cancer cells have certain gene changes. These include changes to
In this trial, they are looking at a new drug called entrectinib, also known as GO40782 .
Entrectinib is a type of targeted cancer drug called a
We know from research that entrectinib has helped a small number of people whose cancer cells have these gene changes. Researchers now want to test it in a larger group of people.
The aims of the trial are to:
- find out how safe treatment is
- find out how well it works
- learn more about the side effects
Who can enter
The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.
You might be able to join this trial if all of the following apply.
- You have a solid tumour that has spread into surrounding tissues or elsewhere in the body or you have anaplastic large cell lymphoma
- There is a sample of tissue (
biopsy) available for the trial team to do some tests on that show your cancer cells have certain gene changes, or you are willing to have a new sample taken
- Your cancer cells have gene changes that include NTRK1/2/3 or ROSI
- Your cancer can be seen and measured on a scan
- You are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
- You have satisfactory blood test results
- You are at least 18 years old
You cannot join this trial if any of these apply.
- Have cancer that has spread to your brain or the membranes surrounding the brain (leptomeningeal disease). But you might be able to join if you have had treatment for this or the cancer isn’t causing symptoms.
- Have already had treatment such as crizotinib, ceritinib, alectinib, lorlatinib or larotrectinib (LOXO-101) that targets the same gene changes as entrectinib in the cancer cells
- Have had chemotherapy or a targeted cancer drug that has not completely cleared your body
- Have had
monoclonal antibodytreatment in the last 4 weeks
- Have had radiotherapy within 14 days of starting trial treatment or you finished stereotactic radiosurgery to the brain within 7 days
- Are having treatment as part of another experimental trial
- Have had another cancer in the past that might interfere with how entrectinib works
- Haven’t fully recovered from surgery
- Have problems with your heart, such as a heart attack in the last 3 months, angina that is not well controlled, an abnormal heart rhythm that needs treatment, congestive heart failure or a heart artery bypass operation
- Have had a stroke or a mini stoke (TIA) in the last 3 months
- Have extra risk factors for a heart condition called torsade de pointes such as a family history of an abnormal heart rhythm called long QT syndrome
- Have a lung condition called interstitial lung disease or inflammation in the lung caused by having a targeted cancer drug called a
tyrosine kinase inhibitor
- Have had problems with your
digestive systemsuch as Crohn’s disease or ulcerative colitis that might interfere with how you absorb the trial drug
- Have a history of or there is someone in your family with a history of bone disease
- Have significant numbness or tingling in your hands or feet (
- Have an infection that might affect how entrectinib works
- Have HIV
- Have any other serious medical condition or mental health problem that the trial team think could affect you taking part
- Can’t swallow capsules without chewing, crushing or opening them
- Are pregnant or breastfeeding
This phase 2 trial is taking place worldwide. The researchers need 400 people to take part including at least 13 from the UK. They are mainly looking at solid tumours such as:
non small cell lung cancer
- bowel cancer
- soft tissue
sarcoma head and neck cancer melanoma skin cancer
- cancer of the
- women’s cancers such as ovarian or womb cancer
Everybody who agrees to take part will have a tissue sample (biopsy) tested for the specific gene changes. The researchers might be able to test a sample that was taken when you had surgery or a biopsy. Or they might ask to take a new sample. The test is done in a specialist laboratory. It takes about 3 to 4 weeks to get the results.
If the test results show that you don’t have the specific gene changes, you won’t be able to take part in the trial. Your doctor will discuss other treatment options with you. If you have the gene changes, you might be suitable to join depending on the results of the other tests you have done before you join the trial.
Entrectinib is a capsule. You take the capsules once a day, everyday.
You have treatment for as long as it is helping you and the side effects aren’t too bad.
Samples for research
The doctors will ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests. They plan to use these samples to look at:
- what happens to entrectinib in the body (
- substances called
biomarkersto help work out why treatment might work for some people and not for others
The doctors are also looking at your genetic material (DNA) found in your body cells. They will test samples of your blood to find out whether your cancer cells have DNA changes that show up in these samples.
Knowing more about people’s genetic material might help the doctors to understand why cancer can behave differently in different people and how their bodies respond to treatment.
When you finish treatment, the trial team might ask to take a tissue sample (a biopsy). You don’t have to agree to this if you don’t want to. You can still take part in the trial.
The trial team hope to use any leftover samples for future research.
Quality of life
The trial team will ask you to fill out some questionnaires on an electronic device similar to an iPad. You do this before you start treatment and at set times during treatment.
The questionnaire asks about side effects and how you’ve been feeling. This is called a quality of life study. This should take about 15 to 20 minutes to complete.
You see the trial team and have some tests before you start treatment. The tests include:
- physical examination
- blood and urine tests
- heart trace (
- CT scan or MRI scan of the brain, chest and tummy (abdomen)
- heart scan (
echocardiogram) or MUGA scan
- bone scan and bone density scan
- PET scan
You have your first dose of entrectinib at the hospital. You’ll need to stay for about 4 hours afterwards to have an ECG and some blood tests. But you should be able to go home after that.
You should take your capsules at home as directed. On hospital visit days, you may need to take them at the hospital rather than at home. The trial team can tell you more. They will give you a fresh supply of capsules each month.
You go to hospital for blood tests and a check up:
- twice a month for 3 months
- once a month after that
You have a CT scan or MRI scan:
- once a month for 2 months
- every 2 months
You have some scans to check how healthy your bones are. You have these:
- after 6 months of treatment
- after every 12 months of treatment
- when you finish treatment
You see the trial team a month after you finish treatment for a check up and some blood tests. They will repeat some of the tests you had done when you joined the trial.
You continue to have scans every 2 months if you stopped treatment but your cancer hasn’t got worse.
A member of the trial team will phone you or check your medical notes every 3 months to see how you are getting on.
The trial team monitor you during the time you have treatment and you have a phone number to call them if you are worried about anything.
We know from trials of entrectinib in people with advanced cancer that it causes certain side effects. In these trials, very common side effects happen in more than 10 out of 100 people (10%).
The very common side effects of entrectinib include:
- feeling weak or lack of energy (fatigue)
- tingling, tickling, prickling, or burning sensation of the skin
- skin rash that may be red and itchy, with small bumps on the skin
- feeling sick (nausea) or being sick (vomiting)
- taste changes
- muscle, joint, bone or tummy (abdominal) pain
- memory problems
- changes in sleep (sleep disturbances)
- swallowing problems
- diarrhoea or constipation
- weight gain
- low levels of
white blood cellsor red blood cells
- increased levels of creatinine in the blood – this could affect how your kidneys work
- swelling or fluid retention of the face, arms, or legs, or a part of the body
- urine infections
- loss of muscle control and balance
- shortness of breath
- cough, colds or pneumonia
- loss of appetite
- increased risk of infection
- liver changes
- blurred vision
- low blood pressure
The trial doctors explain all the possible side effects before you join the trial.
How to join a clinical trial
Dr Simon Pacey
F . Hoffman - La Roche, Limited