A study looking at lorlatinib for advanced non small cell lung cancer (ALKALINE)

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

Cancer type:

Lung cancer

Non small cell lung cancer

Status:

Closed

Phase:

Phase 2

This study is looking at lorlatinib for non small cell lung cancer (NSCLC) that has a change mutation Open a glossary item in a gene called anaplastic lymphoma kinase (ALK). This is called ALK positive disease.

It is open to people whose cancer got worse during treatment with one of the following:

ceritinib
alectinib
brigatinib

If you are still having treatment with one of the above and it is still working you may be able to join a sub study Open a glossary item that is part of this study.

More about this trial

Doctors use targeted drugs Open a glossary item called growth blockers such as ceritinib, alectinib and brigatinib to treat NSCLC that has an ALK gene change.

Sometimes treatment can stop working because the cancer develops more gene changes. In this study researchers want to find out if this has happened in your cancer and if so what these new changes are.

The standard way of finding this out is by taking a sample of the cancer tissue (biopsy Open a glossary item ). There are 2 main ways to take a biopsy. The first is using a needle (needle biopsy). The doctor puts a needle through the skin into the lung where the cancer is. They take out a small piece of the cancer tissue using the needle.

The second is a surgical biopsy. The doctor takes a biopsy during an operation.

In this study the team are looking at another way of looking for these gene changes. This is by taking blood samples and looking for gene changes in the blood. This is called circulating tumour DNA Open a glossary item (ctDNA). These are tiny bits of DNA of the cancer cells that are in the blood after the cancer cell has died.

As part of the study you take lorlatinib. This is also a growth blocker. Doctors already use this to treat NSCLC with an ALK gene change.

The main aims of the study are to find out:

how well lorlatinib works after the cancer continued to get worse after similar treatments
who might benefit most from having lorlatinib based on gene changes
more about the side effects of lorlatinib after having similar treatments
how lorlatinib affects quality of life

Who can enter

The following bullet points are a summary of the entry conditions for this study. Talk to your doctor or the study team if you are unsure about any of these. They will be able to advise you.

Who can take part

You may be able to join this study if all of the following apply. You:

have NSCLC that has a change in the ALK gene
have stage 3 NSCLC that cannot be treated by surgery or radiotherapy. Or you have NSCLC that has spread (stage 4).
had as your latest treatment either ceritinib, alectinib or brigatinib and your cancer got worse during this treatment
have an area of cancer that the doctor can measure on a scan
are willing to give a blood sample
have satisfactory blood test results
are willing to use contraception during treatment and for a time after if there is any chance you or your partner could become pregnant
are up and about, can look after yourself but might not be able to work (performance status 0, 1 or 2)
are at least 18 years old

Who can’t take part

Cancer related
You cannot join this study if any of these apply. You:

have symptoms of cancer spread to the brain or the tissue surrounding the brain that isn’t controlled
have spinal cord compression unless you have had treatment, your pain is controlled and is stable 3 weeks before starting treatment
have finished any other cancer treatment including as part of another clinical trial within a certain time of starting treatment. Your doctor will know how long this is.
have moderate to severe ongoing side effects of any previous treatment
have had another cancer within the past 3 years. This is apart from non melanoma skin cancer , any carcinoma in situ (CIS), papillary thyroid cancer and early prostate cancer if they have been successfully treated.

Medical conditions
You cannot join this study if any of these apply. You:

have major surgery within 4 weeks of starting treatment. If you have had surgery before this time the wound must be completely healed within 3 weeks of starting treatment. For minor surgery the wound must be completely healed within 1 week of starting treatment.
have had radiotherapy within 2 weeks of joining the study. You may be able to take part if you have had radiotherapy for symptom control (palliative) and this finished at least 2 days before you join the study. If you have had radiotherapy to the brain, this must be complete at least 2 weeks for a small area, or 4 weeks for the whole brain.
have active hepatitis B, active hepatitis C, HIV or any other infection that needs treatment
have a heart problem that could affect your taking part. Your doctor will know more about this.
have or had a medical condition that affects the lung tissue including inflammation of the lung not caused by an infection that needed treatment with steroids . This is apart from COPD and inflammation caused by radiotherapy.
have a digestive system problem that affects how well your body can absorb medication
are not able to swallow tablets
are taking medication including herbal supplements that affects the CYP enzymes. Your doctor will know which ones these are.
have a problem with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption that has been passed down through the family (hereditary )
have any other medical condition, mental health problem or social situation that could affect you taking part

Other
You cannot join this study if any of these apply. You:

are allergic or sensitive to lorlatinib or any of its ingredients
are pregnant or breastfeeding

Trial design

This is an international phase 2 study. The team need 84 people to join the study.

Main study
Everyone in the main study has lorlatinib.

Lorlatinib is a tablet. You take it once a day. You continue taking lorlatinib as long as it is helping and the side effects aren’t too bad.

Sub study
You can join the sub study Open a glossary item if you are still having treatment with:

ceritinib
alectinib
brigatinib

And your treatment is still working.

While your treatment is working you won’t have lorlatinib. But if your cancer starts to grow again while on treatment your doctor might invite you to take part in the main study.

Samples for research for the main study and sub study
You give blood samples when you join then every 3 months while having treatment. Where possible, the team will take these samples when you have blood samples taken as part of your routine care.

You give another blood sample if your cancer comes back while having lorlatinib.

Researchers will use these samples to look at specific changes in ALK and other genes. They want to find out how gene changes affect the way the treatment works.

They are also looking at whether there is enough genetic information such as circulating tumour DNA Open a glossary item (ctDNA) in the blood samples to show how well treatment is working.

Optional samples for research for the main study
Using blood samples is a new way of checking how well treatment is working. So the team want to check that the information is the same as the standard way of checking. The standard way is to take samples of tissue (biopsy Open a glossary item ) from the cancer.

The team will ask you for 2 tissue biopsies. The first is before you start lorlatinib. The second is if and when your cancer starts to grow.

Your doctor will make sure it is safe to take a biopsy before taking them.

The team will check the information taken from the blood samples with the information from the biopsies. They hope this can help them decide how to best use these blood samples. And whether blood samples can replace biopsies to check how well treatment is working.

You don’t have to agree to have the biopsies taken. You can still take part in the main study.

Quality of life
As part of the main study you fill in a questionnaire. You fill it in before starting lorlatinib and at regular times during the first year of treatment.

The questions ask about:

your general health and wellbeing
what you can do in your daily life
any signs or symptoms

This is a quality of life questionnaire.

Hospital visits

Main study
You see the doctor for tests before taking part. These include:

a physical examination
blood tests
urine test
heart trace (ECG)
heart scan (ECHO)
eye test with an eye specialist if your doctor thinks it is needed
CT scan or MRI scan
MRI scan of the brain

During treatment you see the doctor regularly. This is for blood tests and to see how you are.

You have the same scan you had at the start and an MRI of your brain:

every 8 weeks for 40 weeks
then every 12 weeks

At the end of treatment you see the doctor for tests, blood tests and to see how you are.

You then see the doctor:

every 8 weeks for 40 weeks
then every 12 weeks

If your cancer gets worse while having lorlatinib, you see the doctor or they will phone every 3 months to see how you are.

Sub study
There are no extra hospital visits if you take part in the sub study.

Side effects

The study team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.

The most common side effects of lorlatinib are:

an increase in the amount of cholesterol and fats in the blood
swelling of your skin or arms and legs
eye problems such as double vision, difficulty seeing with one or both eyes
nerve changes that can affect your walking and cause pins and needles in your hands or feet
changes to how your pancreas works
diarrhoea or constipation
a drop in red blood cells (anaemia) causing tiredness and breathlessness
joint and muscle pain
weight gain
headaches
skin rash