A study of AZD6738 for advanced cancer (Dose escalation study)

Cancer type:

All cancer types
Head and neck cancers
Laryngeal cancer
Lung cancer
Mouth (oral) cancer
Nasal and paranasal sinus cancer
Nasopharyngeal cancer
Non small cell lung cancer
Pharyngeal cancer
Salivary gland cancer

Status:

Open

Phase:

Phase 1

This study is looking at AZD6738 for solid cancers that have spread to another part of the body. A solid cancer Open a glossary item is any cancer apart from cancers of the blood such as leukaemia and lymphoma.

There are 2 parts to this study. This summary is about the dose escalation study. We have another summary about the dose expansion study

More about this trial

AZD6738 is a new drug. It works by stopping a protein called ATR. A change (mutation Open a glossary item) in the ATR protein causes some cancers to grow and multiply.

Researchers think AZD6738 combined with other anti cancer drugs might work well to stop cancer growing.

But first they need to find the best dose of AZD6738 to give by itself and in combination with the other drugs.               

Who can enter

The following bullet points list 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.

You may be able to join the study if you are in one of the following situations.

You have solid cancer Open a glossary item that has spread to another part of the body and there is no further standard treatment Open a glossary item.

Or

You have non small cell cancer (NSCLC) and:

  • Your cancer has spread into the surrounding tissue (locally advanced) or has spread to another part of the body
  • Your cancer has come back after or continued to grow during your first course of chemotherapy treatment (first line treatment Open a glossary item)
  • There is no further standard treatment
  • You have at least 1 area of cancer that measures 10mm or more across (15mm or more for a lymph node Open a glossary item) that can be seen on a scan and hasn’t be treated with radiotherapy

Or

You have a head and neck cancer that is a squamous cell cancer Open a glossary item and:

  • Your cancer has spread into the surrounding tissue (locally advanced) or has spread to another part of the body
  • Your cancer has come back after or continued to grow during your first course of chemotherapy treatment (first line treatment)
  • Your chemotherapy included 5FU and a platinum drug such as carboplatin or cisplatin
  • There is no further standard treatment
  • You have at least 1 area of cancer that measures 10mm or more across (15mm or more for a lymph node) that can be seen on a scan and hasn’t be treated with radiotherapy

Please note that people with a head and neck cancer can't join the trial at the moment. 

And all of the following apply, you:

  • Have satisfactory blood test results
  • Are fully active but can’t do heavy physical work (performance status 0 or 1) and this hasn’t got worse in the past 2 weeks
  • Are willing to use reliable contraception during treatment and for at least 6 months afterwards if there is any chance you or your partner could become pregnant
  • Are at least 18 years old

You cannot join this study if any of these apply.

Cancer related

  • Your cancer is pressing against your spinal cord (spinal cord compression Open a glossary item)
  • Your cancer has spread to the brain unless you have no symptoms, it is stable and you have not been taking steroids for at least 4 weeks before starting treatment in this study
  • You have had any anti cancer drug treatment in the past 4 weeks
  • You have had radiotherapy within 4 weeks of starting treatment, 1 week if it was a small area to relieve symptoms apart from radiotherapy to more than 30% of the bone marrow Open a glossary item
  • You have ongoing side effects from previous treatment apart from hair loss
  • You have had steroids within the 4 weeks before starting treatment
  • You have had an experimental drug as part of a clinical trial within 4 weeks of starting treatment
  • You have had another cancer in the past 3 years apart from cervical intra epithelial neoplasia (CIN Open a glossary item) and non melanoma skin cancer Open a glossary item

Medical conditions

  • You have ataxia telangiectasia
  • You have had a heart attack in the past 6 months or another heart problem such as heart failure, unstable angina or unstable heart rhythm
  • You have high blood pressure that isn’t controlled by medication
  • You have a problem with your digestive system Open a glossary item such as Crohn’s disease or IBS that could affect how AZD6738 is absorbed
  • You have fits (seizures) that can’t be controlled  with medication
  • You have an infection that needs to be treated with drugs such as antibiotics that reach your whole body (systemic treatment Open a glossary item)
  • You have HIV, hepatitis B or hepatitis C
  • You have any other medical or mental health condition that the team think could affect you taking part in the study

Other

  • You are taking any medication that affects the CYP enzymes or the Pgp protein
  • You have had AZD6738 or any drug that works in the same way
  • You are allergic to AZD6738 or any of its ingredients
  • You have had olaparib, or a similar drug, before
  • You are pregnant or breastfeeding

There are different parts to the study and you might not be able to join a certain part if any of the following also apply. You:

  • Are not able to have carboplatin
  • Have or might have myelodysplastic syndrome (MDS)
  • Have or might have acute myeloid leukaemia (AML)
  • Have had a biological therapy Open a glossary item as part of a clinical trial in the past 7 weeks
  • Have had a blood transfusion in the past 4 months
  • Have a blockage of the gut
  • Have severe bleeding of the food pipe (oesophagus) or stomach within the 4 weeks of starting treatment
  • Are allergic to olaparib or any of its ingredients
  • Are allergic to durvalumab (MEDI4736) or any of its ingredients
  • Have had medication that affects the immune system Open a glossary item such as steroids within 4 weeks
  • Have had a live vaccine Open a glossary item within a month of starting treatment
  • Have or have had sarcoidosis Open a glossary item
  • Have or have had tuberculosis Open a glossary item

Trial design

There are separate parts to this study. Which part you are in will depend on your cancer type and when you join.

This is a phase 1 study. The study team need about 156 people in total to take part.

The first few people to take part will have a low dose of AZD6738. If they don’t have any bad side effects the next few will have a higher dose. And so on until the highest safe dose is found. This is a dose escalation study

After this they want to find the best dose of AZD6738 to give with:

They do this the same way as above. Which drug you have depends on your type of cancer.

AZD6738 is a tablet. You take it on an empty stomach. You can’t eat or drink anything apart from water for 2 hours before, or an hour after, taking your tablets. Your doctor will tell you how many to take.

You have carboplatin as a drip into a vein every 3 or 4 weeks. You have 6 treatments.

Olaparib is a tablet. Your doctor will tell you when to take them and how many.

You continue having olaparib and AZD6738 for as long as it is helping you and the side effects aren’t too bad.

You have durvalumab as a drip into a vein every 6 weeks. You continue having durvalumab and AZD6738 for as long as it is helping you and the side effects aren’t too bad.

Samples

The researchers will ask for samples of tissue (biopsy Open a glossary item).These might be samples you have had taken previously. Or they may ask you to have a biopsy done while you are in the study.  Not everyone will need to have additional biopsies. It will depend on which part of the study you join. The researchers will explain more.  

You have some additional blood tests as part of this study. These are to measure specific substances in the blood (biomarkers Open a glossary item).

You will be asked if you’re willing to have an extra blood test. This is for genetic research. You do not have to give this sample if you don’t want to. You can still take part in the main study.

The researchers use all these samples to find out more about cancer and how AZD6738 works.

Hospital visits

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

  • a physical examination
  • blood tests
  • heart trace (ECG Open a glossary item)
  • x-ray, CT scan or MRI scan

During treatment you see the doctor regularly and have the same tests. How often you have them depends on which treatment you are having.

A month after finishing treatment you see the doctor and have the same tests.

You then see the doctor every 6 to 8 weeks until your cancer starts to grow again.

Side effects

AZD6738 is a new drug. This is the first time it is being used in humans and there may be side effects we don’t know about yet. Side effects of AZD6738 might include:

You are monitored very closely while taking AZD6738. Tell your doctor or nurse if your general health changes while taking AZD6738.

Durvalumab is a new drug and again there may be side effects we don’t know about yet. The most common side effects include:

  • tiredness
  • shortness of breath or difficulty breathing
  • cough
  • inflammation of the airway (bronchitis)
  • feeling or being sick
  • loss of appetite
  • constipation or diarrhoea
  • tummy (abdominal) pain
  • rash, itchy skin
  • back and joint pain
  • a general feeling of being unwell
  • a loss of fluid and minerals from the body (dehydration Open a glossary item)
  • dizziness
  • high blood pressure
  • fluid in the lungs
  • a severe general infection of the body (sepsis)
  • an increase in a liver enzyme
  • mouth sores

We have information on the side effects of:

Your doctor will talk to you about the side effects before you agree to take part. 

Location

Cambridge
London
Manchester
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 Matthew Krebs

Other information

AstraZeneca
Experimental Cancer Medicine Centre (ECMC)

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

14042

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

Cara took part in a clinical trial

A picture of Cara

"I am glad that taking part in a trial might help others on their own cancer journey.”

Last reviewed:

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