A trial looking at different drugs for non small cell lung cancer (National Lung Matrix Trial)

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

Secondary cancers

Status:

Closed

Phase:

Phase 2

This trial is looking at a number of new drugs to treat non small cell lung cancer. The treatment you have depends on changes to genes in your cancer cells.

The trial is supported by Cancer Research UK.

More about this trial

Non small cell lung cancer (NSCLC) is the most common type of lung cancer. There are 2 main types of NSCLC called squamous cell carcinoma and adenocarcinoma. This trial is for people who have one of these types of NSCLC, and surgery or radiotherapy aren’t suitable treatments for them.

Doctors decide how to treat a cancer by looking at:

what type of cancer it is
where it is in your body
the size of the cancer
what the cancer cells look like

This works for many people but not for all. This could be because there are slight differences in the cancer cells from person to person, even if they have the same type of cancer. This is particularly true of lung cancer, where changes to genes in the cancer cells are different from person to person. Genes are coded messages that tell cells how to behave. If a gene is changed it can allow cancer cells to grow.

Identifying the gene changes will allow doctors to specifically target them and try to kill the cancer cells, or stop them growing. Matching treatment to genetic changes in cancer cells is called stratified medicine.

The people taking part in this trial have already agreed to have their cancer tested to look for any gene changes as part of the Cancer Research UK Stratified Medicine Programme (SMP2). They now have treatment depending on the gene changes found in their cancer cells. The researchers want to:

see how well the treatments work and how safe they are
understand more about which genetic changes are linked to drug resistance and why some people benefit from treatment but others do not

Who can enter

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

have non small cell lung cancer that is either squamous cell carcinoma or adenocarcinoma
have cancer that has spread outside your lung (stage 3) and you can’t have surgery or radiotherapy with the aim of curing it, or it has spread to another part of your body (stage 4)
have had all other standard treatments that are suitable for you and your cancer has continued to grow
gave a sample of your tumour in the Cancer Research UK Stratified Medicine Programme (SMP2)
have had a CT scan or MRI scan in the last 4 weeks that shows an area of cancer that can be measured
are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1). Depending on which treatment group you are in you may be able to take part if you 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 at least 18 years old
are willing to use reliable contraception during the trial and for at least 3 months after you finish treatment if there is any chance you or your partner could become pregnant. Depending on which treatment you have, you may need to use contraception for longer than 3 months afterwards (the trial team will advise you about this)

You cannot join this trial if any of these apply. You:

have cancer that has spread to your brain or is pressing on your spinal cord (spinal cord compression), unless this has been treated, is not getting worse or causing any symptoms, and you haven’t needed to take steroids for at least 4 weeks
have had major surgery, chemotherapy or radiotherapy, or any other anti cancer treatment (including experimental drugs) in the last 4 weeks
have any long term problems with your digestive system that could affect how you absorb drugs
have had any other cancer in the last 3 years apart from carcinoma in situ of the cervix or basal cell skin cancer that was successfully treated
are still having side effects from earlier cancer treatment unless they are very mild (apart from hair loss)
have HIV, hepatitis B or hepatitis C
have certain heart problems (the trial team can advise you about this as it will depend on which treatment you have)
have any other medical condition or mental health problem that the trial team think could affect you taking part
are pregnant or breastfeeding

There are some other things that would mean you can or can’t join different treatment groups in the trial (the trial team can advise you about this).

Trial design

This is a phase 2 trial. The researchers want to screen about 2,000 people. They hope that about 610 of them will be able to join the trial.

The people taking part are put into treatment groups according to gene changes that have been identified in their cancer cells. At present there are only a limited number of drugs available which can be matched to an individual gene change.

If one of these gene changes has been found in your cancer cells, you are put into one of the following groups:

people in group A have a drug called AZD4547 - this group is now closed to recruitment
people in group B have a drug called vistusertib (AZD2014)
people in group C have a drug called palbociclib
people in group D have a drug called crizotinib
people in group E have a drug called selumetinib and a chemotherapy drug called docetaxel
people in group F have a drug called AZD5363 - this group is now closed to recruitment
people in group G have a drug called osimertinib - this group is now closed to recruitment
people in group H have a drug called sitravatinib - this group is now closed to recruitment
people in group J have a drug called AZD6738 and durvalumab

If you don’t have a gene change that can be matched to a drug, you will be in a group called NA or NAJ:

people in group NA had a drug called durvalumab (MEDI4736) - this group is now closed to recruitment
people in group NAJ have a drug called AZD6738 and durvalumab (MEDI4736)

There is no evidence that the activity of durvalumab is dependent upon the presence of any specific gene changes.

As the trial goes on, the research team may identify other drugs that they think could work for people with certain genetic changes. If that happens, they will add new groups.

The trial team will give you more information about the treatment you are going to have. They will also explain how and when you have the treatment and how long it will last.

Hospital visits

You see the trial team and have some tests before you start treatment. The tests include:

physical examination
blood tests
urine test
heart trace (ECG)
a test to measure the amount of carbon monoxide in your breath
CT scan

Depending on which treatment group you are in, you may also have:

a heart scan (MUGA scan or echocardiogram)
an eye examination

The researchers will need to test a sample of your cancer before you can take part in the trial. There may be enough tissue left from the sample you gave for the SMP2 study. But if there isn’t enough tissue left after the tests that were done, or you have had certain types of treatment since giving that sample, you will need to have a new biopsy that the researchers can test.

It is possible to get important information from tiny amounts of cancer related material in your bloodstream. This is known as circulating tumour DNA or ctDNA. It is possible to track how your cancer changes over time by looking at changes to the ctDNA before, during and after treatment. It may also be possible to identify which changes are linked to drug resistance. Throughout the trial, you give a number of blood samples to look at this.

The trial team will also ask you to have a biopsy before starting treatment and another when you finish treatment. This is to help them understand more about why some people benefit from treatment and others do not. But you don’t have to agree to have these 2 extra biopsies if you don’t want to. You can still take part in the trial.

How often you go to hospital for treatment will depend on which group you are in. You have a CT scan every 6 weeks during treatment for the 1st year. You then have a CT scan every 12 weeks.

The trial team will tell you more about the hospital visits you will need to make, and any tests you will have during the trial and after you finish treatment.

Side effects

As some of the drugs being looked at in this trial are new, there may be side effects we don’t know about yet.

The trial team will talk to you about all the possible side effects of the drug (or drugs) you will be having before you agree to take part.

Early results

In 2020 the trial team published some early (interim) results for some of the groups in the National Lung Matrix Trial.

There are lots of different treatment groups in this trial and we don’t have results for all them yet. Some groups are still open for people to join (see ‘Trial design’ section above).

This is a summary of the results so far. We plan to update this page when more results are available.

Results
As of November 2019, the research team had looked for genetic changes in the lung cancer cells of 5,467 people:

2,007 people (37%) had a genetic change meaning they would be eligible to join the trial
288 people had joined the trial

14 of these 288 people had treatment as part of this trial, and then joined the trial again and had a different treatment.

Group A
This group was for people with a change to the FGFR2 or FGFR3 gene. They had a drug called AZD4547.

The research team had to close this group earlier than planned because the company stopped making AZD4547 part way through. At the time there were 5 people in the group, and the cancer had got smaller in 1 person.

Group B
There are several sub groups in Group B. People in these groups had a targeted cancer drug called vistusertib.

Group	Gene with change	Time until the cancer started to grow again	Number of people whose cancer got smaller
B1	TSC1 or TSC2	2.1 months	0 out of 5
B2S	STK11	2.3 months	0 out of 17
B2D	KRAS and STK11	2.9 months	2 out of 25

Group C
There are several sub groups in Group C. People in these groups had a targeted cancer drug called palbocicilib.

There are 2 groups for people with a change in the CDKN2A gene:

C1 is for people with a type of cancer called squamous cell cancer
C2 is for people with a type of cancer called adenocarcinoma

Group	Gene with change	Time until the cancer started to grow	Number of people whose cancer got smaller
C1	CDKN2A	4.2 months	0 out of 19
C2	CDKN2A	3.3 months	1 out of 27
C3	CDK4	2.2 months	0 out of 8
C4	CCND1	3.7 months	0 out of 15
C5	KRAS and STK11	2.6 months	0 out of 12
C6	KRAS	5.3 months	1 out of 30

Group D
There are several subgroups in Group D. People in these groups had a targeted cancer drug called crizotinib.

Group	Gene with change	Time until the cancer started to grow	Number of people whose cancer got smaller
D1	MET	3.8 months	0 out of 13
D2	ROS1	3 years and 9 months	5 out of 7
D3	MET exon 14	12.5 months	8 out of 12

Group D2 is now closed because crizotinib has been licensed as a treatment for this group of patients.

Group E
There are several subgroups in Group E. People in these groups had a targeted cancer drug called selumetinib and a chemotherapy drug called docetaxel.

There are 2 groups for people with a change in the NF1 gene:

E1 is for people with a type of cancer called squamous cell cancer
E2 is for people with a type of cancer called adenocarcinoma

Group	Gene with change	Time until the cancer started to grow	Number of people whose cancer got smaller
E1	NF1	We don't have the results for this group yet
E2	NF1	5.3 months	4 out of 14
E3	NRAS	We don't have the results for this group yet

Group F
The people in this group had changes to the PIK3CA, PTEN or AKT gene. They had a targeted cancer drug called capivasertib.

The cancer didn’t get smaller in any of the 28 people in Group F. So the research team decided to close this group.

Group G
This group was for people with a change in the EGFR gene. They had a targeted cancer drug called osimertinib.

Group	Gene with change	Time until the cancer started to grow	Number of people whose cancer got smaller
G1	EGFR	1 year and 3.5 months	8 out of 10

Group G1 is now closed because osimertinib has been licensed as a treatment for this group of patients.

Group H
This group is for people with a change in the RET gene. They had a targeted cancer drug called sitravatinib.

The trial team closed this group after research showed that other treatments worked for people with changes in the RET gene.

Group J
This group is for people with a change in the KRAS gene. They had targeted cancer drugs called ceralasertib and durvalumab.

We don’t have results for this group yet. We will update this information when the results are available in the future.

Group NA1
This group is for people who didn’t have a specific genetic change that could be matched to a drug. They had a targeted cancer drug called durvalumab.

This group is now closed but we don’t have the results yet. We will update this information when the results are available in the future.

Group NAJ
This group is also for people who didn’t have a specific genetic change that could be matched to a drug. They have targeted cancer drugs called ceralasertib and durvalumab.

We don’t have results for this group yet. We will update this information when the results are available in the future.

Smoking history
The research team looked at the differences between people who had smoked for a long time, those who smoked for short time and those who had never smoked.

They found that:

treatment often worked better for people who had never smoked, or had only smoked for a short time
people with squamous cell carcinoma who smoked did worse than those with other types of lung cancer

Conclusion
The research team have concluded that, so far, some treatments have not worked as well as they had hoped. Even when laboratory work has shown that a particular drug may work for people with a specific genetic change.

They hope to open new groups so they can look at different treatments.

They also suggest that treatment is more likely to work for people who have never not smoked, or not smoked for very long.

Where this information comes from
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.