A trial of AZD9291 for non small cell lung cancer that has got worse despite having a particular type of drug that blocks cancer growth (AURA)

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 1/2

This trial is looking at a new drug called AZD9291 for non small cell lung cancer that has got worse despite having a type of drug called a tyrosine kinase inhibitor.

If non small cell lung cancer cells have changes to certain genes, they produce proteins called epidermal growth factor receptors. If your lung cancer has these receptors, it is called EGFR positive cancer.

If you have EGFR positive lung cancer, you may have a drug called a tyrosine kinase inhibitor (TKI). Some TKIs such as erlotinib and gefitinib work by blocking receptors for the epidermal growth factor proteins.

But after a period of time, lung cancer can stop responding to TKIs. This is due to another gene change called T790M. Researchers are looking for new treatments to help people in this situation.

In this trial, they are looking at a drug called AZD9291 which works against both the original gene change and T790M. It may help people whose cancer has started to grow again despite having a TKI. It may also slow down the development of the T790M gene change in the cancer. So, the response to the TKI may last longer.

This is the first time the drug has been tested in people. The aims of the trial are to

  • Find the highest safe dose of AZD9291
  • Learn more about the side effects and what happens to the drug in your body
  • See how non small lung cancer with the T790M gene change responds to AZD9291

Who can enter

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

  • You have non small cell lung cancer and an X-ray or CT scan shows it got worse during your last treatment
  • Your last treatment was a tyrosine kinase inhibitor drug such as erlotinib or gefitinib (some people may be able to join if they haven’t had this type of treatment, but the trial doctor can explain this)
  • Your cancer has a gene change that is known to make it sensitive to drugs targeting EGF receptors, or your cancer initially responded to a drug that targets EGF receptors but then started to get worse (your doctor can confirm this)
  • You have at least 1 area of cancer that hasn’t been treated with radiotherapy, is bigger than 10mm in size (15mm if it is a lymph node) and can be seen and measured on an X-ray or CT scan
  • You have satisfactory blood test results
  • You are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
  • You are at least 18 years old
  • You are willing to use reliable contraception during the trial and for 3 months afterwards if there is any chance you or your partner could become pregnant

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

  • Have cancer that is pressing on your spinal cord (spinal cord compression)
  • Have cancer that has spread to your brain unless this isn’t causing any symptoms, is not getting worse, and hasn’t been treated with steroids in the last 4 weeks
  • Have had major surgery in the last 4 weeks
  • Have a drug such as gefitinib or erlotinib in the 8 days before you start the trial treatment (or earlier if there is a chance that any of the drug could still be in your body)
  • Have chemotherapy, an experimental drug or any other drug for advanced NSCLC in the 2 weeks before you start the trial treatment
  • Have already had AZD9291 as part of this trial
  • Have had radiotherapy in the last 4 weeks, or in the last week if it was radiotherapy for symptoms to one area of your body
  • Need to carry on taking medication that can affect a body protein called CYP3A4 (your doctor can explain this)
  • Haven’t recovered from side effects of earlier treatment unless they are very mild (apart from hair loss or nerve damage caused by a platinum chemotherapy drug if it is only mild)
  • Have HIV, hepatitis B or hepatitis C
  • Have (or have had) certain heart or lung problems (the trial team can advise you about this)
  • Have any other medical condition that the trial team think could affect you taking part
  • Have any problems with your digestive system that could affect how you swallow or absorb the trial drug
  • Are known to be very sensitive to anything that AZD9291 contains or to similar drugs
  • Are pregnant or breastfeeding

Trial design

This is an international trial. The researchers need about 375 people to join. Everybody taking part has AZD9291. It comes as tablets or capsules that you swallow once a day.

The trial is in 2 parts. In the first part of the trial, the researchers want to find the highest dose of AZD9291 that you can have safely. The first few people taking part will have a low dose. If they don’t have any serious side effects, the next few patients will have a higher dose. And so on, until they find the best dose to give. This is called a dose escalation study.

For some of the doses they test, the trial team will recruit more people. This is called an expansion study. They can only recruit people into the expansion study if they know whether or not their cancer has the T790M gene change.

In the 2nd part of the trial, the researchers want to learn more about the side effects of AZD9291 and whether or not lung cancer with the T790M gene change responds to it. Only people whose cancer has the T790M gene change can join this part of the trial.

Whichever part of the trial you join, as long as you don’t have bad side effects, you can carry on taking AZD9291 for as long as it helps you.

If you join the expansion study or the 2nd part of the trial, the researchers will ask you to fill out a questionnaire before you start treatment, every 6 weeks during treatment and after you finish treatment. The questionnaire will ask about side effects and how you’ve been feeling. This is called a quality of life study.

The trial team will ask a small number of people taking part to agree to give samples of their cancer (biopsies) at 2 different times during treatment. This will help the researchers to understand more about this type of cancer and the effect of AZD9291.

They will ask other people to have a biopsy after 2 weeks of treatment and when they finish treatment. But you don’t have to have these biopsies if you don’t want to.

They will also ask about 50 people to take part in 2 interviews. The first one will be 4 to 6 weeks after starting treatment. The second will be after 4 to 6 months.

If you agree to do this, an independent researcher will phone you and ask about any side effects you have and the impact they have on your life. They will make an audio recording of the interview. All the information you give will be confidential. It will not be possible to identify you in any results from the trial. You don’t have to agree to be interviewed if you don’t want to. You can still take part in the trial.

Hospital visits

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

  • Physical examination
  • CT scan or MRI scan
  • 3 heart traces (ECGs)
  • Blood tests
  • Urine test
  • Eye tests

If you join the dose expansion study or the 2nd part of the trial, the researchers need to look at a sample of your cancer to see whether or not it has the T790M gene change. To do this, you will need to have a biopsy. If you have had a recent biopsy, the researchers can use this. But it must have been taken since your cancer started to get worse during other treatment.

If you join the dose escalation study, you start by having 1 dose of AZD9291, followed by a number of blood tests and heart traces (ECGs) over the next few days. The trial team will tell you more about what happens at these hospital visits. Then you start taking AZD9291 once every day.

If you join the expansion study or the 2nd part of the trial, you take AZD9291 every day from the start.

While you are taking daily AZD9291, you see the trial team

  • Once a week for the first 3 weeks
  • Twice in the next week
  • Once every 3 weeks for about the next 3 months
  • Then every 6 weeks until your doctor thinks you are no longer benefiting from the trial treatment

You have regular blood tests, urine tests and some more ECGs. You have a CT or MRI scan every 6 weeks.

The trial team will ask you to have a lumbar puncture at some point during your treatment. They do this to get a sample of the fluid that circulates around your brain and spinal cord (cerebrospinal fluid). You don’t have to have the lumbar puncture if you don’t want to. You can still take part in the trial.

If you join the 2nd part of the trial you also have a heart scan (echocardiogram) or MUGA scan every 3 months.

If you take part in a phone interview, this will last about an hour.

When you finish treatment, you see the trial team once more. A member of the team will then contact you 4 weeks later to see how you are.

If you are in the 2nd part of the trial, the trial team will continue to contact you or your doctor every 6 weeks to see how you are, and find out whether you’ve started any other treatment.

Side effects

This is the first time AZD9291 is being tested in people and there may be side effects we don’t know about yet. The possible side effects include

  • Diarrhoea
  • Skin rash or dry skin
  • Changes to your nails
  • Heart problems
  • Dry eyes
  • Problems swallowing
  • Feeling or being sick
  • Heartburn or indigestion
  • Lung problems such as a cough or shortness of breath (you must tell your doctor straight away if you have these symptoms)

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.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Fiona Blackhall

Supported by

AstraZeneca
Experimental Cancer Medicine Centre (ECMC)

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

Oracle 11726

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Over 60,000 cancer patients enrolled on clinical trials in the UK last year.

Last reviewed:

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