A trial of radiotherapy and targeted treatment for non small cell lung cancer (CONCORDE)

Cancer type:

Lung cancer
Non small cell lung cancer

Status:

Open

Phase:

Phase 1

This trial is to find the best dose of certain targeted drugs to give alongside radiotherapy for people with non small cell lung cancer (NSCLC).

It is for people whose lung cancer hasn’t spread further than the chest. This is called localised lung cancer. 

Cancer Research UK supports this trial.

More about this trial

A combination of radiotherapy and chemotherapy is a usual treatment for people with NSCLC. This is called chemoradiotherapy. This isn’t suitable for everyone so you may have only radiotherapy.

Radiotherapy works by damaging the DNA Open a glossary item inside cancer cells, which could cause them to die. Certain drugs work by stopping cells from repairing damage to their DNA. These drugs are called DNA damage response inhibitors (DDRi). They make it more likely that a damaged cell will die. So researchers think that having a DDRi drug with radiotherapy might improve treatment.

In this trial, researchers are looking at different DDRi cancer drugs. They would like to find out about how well these work with radiotherapy. But first they need to find the best dose of each to give alongside radiotherapy.

Some people have only radiotherapy. And some have radiotherapy and a DDRi. The drug you have depends on when you join the trial. There are 4 groups that are open at the moment. These are:

  • CONCORDE A - looking at a targeted cancer drug Open a glossary item called olaparib
  • CONCORDE B - looking at a new targeted drug called AZD1390
  • CONCORDE C - looking at a targeted drug called ceralasertib. In this group some people also have an immunotherapy drug called durvalumab.
  • CONCORDE E – looking at a new targeted cancer drug called AZD5305. In this group some people also have an immunotherapy drug called durvalumab.

The main aims of the trial are to: 

  • find the best safe dose of each DDRi to have with radiotherapy
  • find out if adding a DDRi to radiotherapy improves treatment 
  • find out if having durvalumab after ceralasertib or AZD5305 and radiotherapy improves treatment 
  • learn more about the side effects 

Doctors hope to run a larger trial when they find the best dose to give.

Who can enter

The following bullet points are a summary of 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. 

Please note, there are several treatment groups so the entry conditions for this trial are complex. Each group has specific entry conditions and we haven’t listed them all.

Who can take part

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

  • have non small cell lung cancer
  • have lung cancer that hasn’t spread outside the chest (stage 2B or stage 3)
  • aren’t suitable to have surgery or a combination of chemotherapy and radiotherapy (chemoradiotherapy)
  • are due to have radiotherapy with the aim to cure as part of your treatment plan (you may or may not be having chemotherapy before the radiotherapy)
  • are suitable to have high doses of radiotherapy (radical radiotherapy)
  • might have had chemotherapy recently but it was within 10 weeks of starting radiotherapy
  • have satisfactory blood test results 
  • don’t have any breathlessness when walking on level ground but you might have some, for example when hurrying up a slight hill
  • can care for yourself but can't carry on with all your normal activities or do active work (Karnofsky Performance status of 70 or more)
  • are willing to use reliable contraception during the trial and for a period after if there is any chance you or your partner could become pregnant 
  • are at least 18 years old

Who can’t take part

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

  • have a mix of non small cell and small cell lung cancer 
  • have NSCLC that got worse after your first chemotherapy (induction chemotherapy) if you have had chemotherapy
  • had a lung function test Open a glossary item that showed your lungs aren’t working well
  • have taken part in a clinical trial or study of a treatment or device within 4 weeks of starting treatment
  • have any other cancer that might affect you taking part in the trial 

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

  • have had radiotherapy to the chest in the past unless you had it for breast cancer and the overlap of the breast  and lung cancer treatment area is small 
  • have had treatment that affects the lungs such as busulfan or bleomycin, within the past year. If you had this treatment a long time ago you might be able to join if it didn’t affect your lungs. And if you had drugs called nitrosoureas Open a glossary item such as carmustine or lomustine in the year before joining the trial. You might be able to take part if the treatment didn’t affect your lungs.
  • have a condition that affects the lungs called interstitial pneumonitis
  • have had a stem cell transplant Open a glossary item with your own cells or somebody else’s or you have had an organ transplant Open a glossary item for example a liver or lung transplant
  • can’t swallow tablets or you have a problem with your gut that means you can’t absorb the medication
  • have an abnormal heart rhythm called QT prolongation
  • have a heart problem such as a heart attack in the last 4 months or high blood pressure that isn’t well controlled with medication
  • have a problem with bleeding that is ongoing
  • have moderate to severe numbness or tingling in your hands or feet
  • have HIV
  • have an active hepatitis B or hepatitis C infection
  • have moderate to severe side effects from treatment apart from hair loss
  • have myelodysplastic syndrome Open a glossary item or acute myeloid leukaemia Open a glossary item or you have symptoms that suggest you might have either
  • have had major surgery within 2 weeks of finding out you are suitable to take part in the trial 
  • have had a chemotherapy drug called gemcitabine within 6 months of joining the trial
  • have severe fits (seizures)
  • have an autoimmune disease Open a glossary item. This is apart from having white patches on your skin (vitiligo), type 1 diabetes, hair loss (alopecia), thyroid Open a glossary item problems that are controlled by medications, a skin condition that doesn’t need treatment or coeliac disease controlled by diet. You might be able to take part if you haven’t had an active autoimmune disease in the last 5 years.
  • have any other medical condition or mental health problem that might affect you taking part in the trial. For example you have an active COVID-19 infection.

Other 
You cannot join this trial if you are pregnant or breastfeeding.

As well as the above there are specific entry conditions and exclusion criteria for each treatment group. Speak to your doctor or research nurse if you want to find out more about the entry conditions for this trial.

Trial design

This is a phase 1 trial. The researchers hope to find 210 people to take part.

It is a randomised trial. You are put into 1 of 2 groups at random by a computer. Neither you nor your doctor can decide which group you are in. You have 1 of the following:

  • 6 weeks of radiotherapy
  • 6 weeks of radiotherapy and a DDRi

The type of DDRi you have depends on when you join the trial. About 50 to 60 of the 210 people taking part have radiotherapy only. The rest have radiotherapy and a DDRi.

For those having a DDRi, the first few people to take part have a low dose of the drug. If they don’t have any bad side effects the next few have a higher dose. And so on until they find the highest safe dose. This is a dose escalation study.

CONCORDE A
In Concorde A you have 1 of the following:

  • 6 weeks of radiotherapy
  • 6 weeks of radiotherapy and olaparib

Olaparib is a tablet. The dose you have depends on when you join the trial. Your doctor tells you how often to take it. 

You start taking it when you start radiotherapy and for the 6 weeks that you have radiotherapy. 

CONCORDE B
In Concorde B you have 1 of the following:

  • 6 weeks of radiotherapy
  • 6 weeks of radiotherapy and AZD1390

AZD1390 is a tablet. You have it either:

  • once a day, Monday to Friday 

or

  • once a day on Mondays, Wednesdays and Fridays 

You start AZD1390 on the same day as you start radiotherapy. You take it for 6 weeks. The dose you have depends on when you join the trial. The trial doctor can tell you more. 

CONCORDE C
In Concorde C, you have 1 of the following:

  • 6 weeks of radiotherapy 
  • 6 weeks of radiotherapy and ceralasertib

Ceralasertib is a tablet. The dose you have depends on when you join the trial. Your doctor tells you how often to take it. You start taking it when you start radiotherapy and for the 6 weeks that you have radiotherapy. 

Some people also have an immunotherapy drug called durvalumab after the 6 weeks of initial treatment. Immunotherapies help the immune system Open a glossary item to find and kill cancer cells. The trial team will talk to you about this. If you are suitable you start this about a month or 2 after you finish radiotherapy. You either have durvalumab on its own or with ceralasertib.

You have durvalumab as a drip into a vein. You have it once a month for up to one year 

CONCORDE E
In Concorde E you have 1 of the following:

  • 6 weeks of radiotherapy
  • 6 weeks of radiotherapy and AZD5305

AZD5305 is a tablet. The dose you have depends on when you join the trial. Your doctor tells you how often to take it. 

You start taking it when you start radiotherapy and for the 6 weeks that you have radiotherapy.

Some people also have an immunotherapy drug Open a glossary item called durvalumab after the 6 weeks of initial treatment. The trial team will talk to you about this. If you are suitable you start this about a month or 2 after you finish radiotherapy. 

You have durvalumab as a drip into a vein. You have it once a month for up to one year.

Radiotherapy
Everyone has radiotherapy as part of the trial. This is a standard treatment. Open a glossary item You have it every week day, Monday to Friday. It takes about 15 minutes each time. You have radiotherapy for 6 weeks. 

Quality of life 
The team ask everybody taking part to fill out a questionnaire before starting treatment, at set times during the trial and after finishing treatment. The questionnaire asks about any side effects you have had and about how you have been feeling. This is called a quality of life study.

Samples for research
The trial team ask you to give some extra blood samples for research. You give these at the same time as your routine samples if possible. 

They’ll also ask for a sample of your cancer that was removed when you had a biopsy Open a glossary item.

Researchers plan to use the samples to look for biomarkers to see who benefits most from having a DDRi added to radiotherapy. 

Hospital visits

You see the doctor and have some tests before taking part. These tests include:

  • a physical examination
  • blood tests
  • urine tests
  • heart trace (ECG Open a glossary item)
  • tests to check how well your lungs work (lung function tests Open a glossary item)
  • chest x-ray
  • CT scan or MRI scan

Those having durvalumab have it at the hospital on the day care ward. And you see the doctor once or twice a month during treatment for a check up. 

You have a check up every week during radiotherapy. When you finish radiotherapy you see the team:

  • 1 month later
  • then every 6 weeks for 6 months
  • then every 3 months for up to 2 years

You have a CT scan at:

  • 1 month 
  • 3 months
  • 6 months
  • 9 months (only if you have durvalumab)
  • 1 year 
  • 1½ years  
  • 2 years 

Side effects

The trial 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. 

AZD1390 is a new drug so there might be side effects we don’t know about yet. The common side effects we do know about include:

Some people with cancer in the brain who had AZD1390 developed:

  • fits (seizures)
  • a problem with the spinal cord causing increased muscle tone in the lower body and legs with muscle twitching. This condition is called Pyramidal Tract Syndrome. But researchers believe this is less likely to affect people with lung cancer. 

AZD5305 is a new drug so there might be side effects we don’t know about yet. The possible side effects that AZD5305 can cause include:

  • feeling or being sick
  • diarrhoea
  • tiredness 
  • a drop in the number of blood cells causing an increased risk of infection, bruising or bleeding, tiredness and breathlessness

The most common side effects of ceralasertib include:

  • constipation or diarrhoea
  • tummy pain
  • indigestion or heartburn
  • feeling or being sick
  • tiredness (fatigue)
  • swelling in the lower legs, hands or both
  • muscle weakness, aches or pains
  • back pain
  • a drop in blood cells causing an increased risk of infection, bruising and bleeding, tiredness and breathlessness
  • runny nose, sore throat or cough
  • cold sores
  • difficulty breathing
  •  inflammation of the lungs (pneumonitis Open a glossary item)
  • weakness, numbness or pain in the hands or feet
  • dizziness
  • loss of appetite
  • high blood sugar
  • itchy skin or skin rash
  • low blood pressure 

Durvalumab can affect the immune system Open a glossary item. This may cause inflammation Open a glossary item and other reactions in different parts of the body. For many people the inflammation and reactions are not too bad. For some people they can cause serious side effects. 

These side effects could happen during treatment or months after treatment has finished. Rarely, these side effects could be life threatening. Your doctor or nurse can explain what these side effects are, the risk of them happening and what to look out for.

If you have any of these side effects tell your doctor or nurse as soon as possible. You should tell them that you are on or have been on an immunotherapy.

 

The most common side effects of durvalumab include:

  • runny nose or sore throat
  • cough
  • low levels of thyroid hormone causing tiredness, weight gain or feeling depressed
  • diarrhoea
  • tummy pain
  • itchy skin or skin rash
  • fever

Some short term side effects of radiotherapy include:

Some long term side effects of radiotherapy include:

  • difficulty swallowing 
  • shortness of breath
  • irritation or damage to the muscle or lining of the heart

We have more information about:

Location

Belfast
Cambridge
Cardiff
Edinburgh
Leeds
London
Manchester
Newcastle upon Tyne
Sheffield
Sutton

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 Alastair Greystoke 
Prof Corinne Faivre-Finn

Supported by

Cancer Research UK
AstraZeneca
Leeds Teaching Hospitals NHS Trust
Newcastle University
University of Glasgow
University of Leeds
University of Manchester

Other information

This is Cancer Research UK trial number CRUK/19/006.

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

16687

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

Last reviewed:

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