A trial using markers to help work out how well new treatments work for triple negative breast cancer (PHOENIX)

Cancer type:

Breast cancer

Status:

Open

Phase:

Phase 3

This trial is using biomarkers to assess how well a new treatment is working. Researchers do this by collecting tumour biopsies  Open a glossary itemand blood samples before and after treatment. This is in the short 2 week period between completing chemotherapy and having surgery.

The trial is looking at different treatments. It is for people who have chemotherapy before surgery but the cancer doesn’t go away completely. 

Triple negative breast cancer is cancer without receptors for:

•    oestrogen Open a glossary item
•    progesterone Open a glossary item
•    HER2 Open a glossary item 

Cancer Research UK supports this trial. 
 

More about this trial

The usual treatment for triple negative breast cancer is chemotherapy followed by surgery. But sometimes the cancer comes back. This risk is higher in people who had chemotherapy but the cancer didn’t go away completely. So researchers want to improve treatment for this group of people. 

In this trial researchers plan to give them treatment in the 2 weeks before surgery to see if this changes how quickly cancer cells are dividing. And how the immune system Open a glossary item is responding to the cancer. Some people also have the same treatment after surgery for up to a year.

To look at the biomarkers Open a glossary item the researchers examine blood and tissue samples (biopsies) Open a glossary item. They compare samples you give before and after treatment. They look for differences in proteins and certain substances (biomarkers). 

In this trial, you have 1 of the following: 

  • no treatment – this is standard care (the control group Open a glossary item)
  • AZD6738 – a new targeted drug Open a glossary item
  • olaparib – a targeted drug called a PARP inhibitor
  • durvalumab – an immunotherapy

The main aims of the trial are to:

  • see how biomarkers change with treatment in the 2 weeks between chemotherapy and surgery 
  • look at different biomarkers to find out what happens to the cancer cells with treatment 
  • identify which drugs could be looked at in a larger trial 
  • learn more about the side effects of treatment
     

Who can enter

The following bullet points list 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. 

Who can take part

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

  • have triple negative breast cancer 
  • have surgery planned after at least 6 cycles  Open a glossary itemof chemotherapy 
  • have cancer that the doctor can measure on a scan
  • have an area of cancer that the doctor can take a tissue sample from 
  • are well enough to have breast cancer surgery with the aim to cure 
  • are fit enough to cope with 2 weeks of treatment after chemotherapy and before surgery 
  • have had scans to check how widespread the cancer is if you have stage 2 breast cancer or stage 3 breast cancer 
  • are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1
  • are suitable to give a tumour sample before and after the 2 week treatment period
  • are willing to use reliable contraception if there is any chance you or your partner could become pregnant and for up to 6 months after the end of trial treatment 
  • are at least 18 years old

As well as the above, to have trial treatment the following must also apply.
You:

  • have an area of cancer left behind after chemotherapy that measures more than 2cm across on a scan
  • have satisfactory blood test results

Who can’t take part

You cannot register to join trial if any of these apply. 

Cancer related
You:

  • have cancer that has spread elsewhere in the body 
  • have cancer in both breasts
  • have had any other cancer in the last 5 years apart from basal cell skin cancer Open a glossary itemsquamous cell skin cancer Open a glossary item or lentigo malinga melanoma 
  • have myelodysplastic syndrome (MDS) Open a glossary item or acute myeloid leukaemia (AML) Open a glossary item
  • have had AZD6738 or a similar drug in the past
  • have had a PARP inhibitor including olaparib in the past
  • have had durvalumab or a similar drug in the past 

Medical conditions
You:

  • have a rare condition called ataxia telangiectasia Open a glossary item
  • have a heart condition called QT prolongation, a family history of QT syndrome or you are taking drugs that cause QT prolongation
  • have treatment to thin the blood including drugs such as warfarin or heparin 
  • have a problem with your gut that means you can’t absorb medication well 
  • have fits (seizures) or a condition that means you might have them
  • have had a stem cell transplant Open a glossary item with somebody else’s cells or a cord blood transplant
  • have an autoimmune disease Open a glossary item unless it is loss of skin pigment (vitiligo), type 1 diabetes, hair loss (alopecia), thyroid Open a glossary itemproblems that are controlled by medications, a skin condition called psoriasis that doesn’t need treatment, coeliac disease controlled by diet or you have an autoimmune condition but you haven’t had any signs or symptoms in the last 5 years 
  • have an active TB infection 
  • have a condition causing lung inflammation that was caused by treatment (pneumonitis)
  • have an active hepatitis B or hepatitis C infection 
  • have HIV
  • have any other medical condition or mental health problem that the trial team think would affect you taking part 

Other
You:

  • are allergic to any of the treatments in the trial
  • can’t swallow tablets 
  • are pregnant or breastfeeding

As well as all of the above, to have trial treatment, the following can’t apply.
You:

  • have a heart problem such as a heart attack in the last 6 months, angina that isn’t controlled with medication, congestive heart failure, an abnormal heart rhythm or high or low blood pressure that isn’t well controlled with medication
  • have fainted (lost consciousness) or had a mini stroke (TIA) within the last 12 months
  • have side effects that aren’t getting better unless they are mild, apart from hair loss
  • have moderate numbness or tingling in your hands or feet caused by treatment 
  • have had major surgery in the last 2 weeks or you aren’t completely better after an operation
  • have had an experimental treatment in the last 30 days 
  • take medication that blocks an enzyme in the body called CYP3A
  • are taking medication that damps down the immune system Open a glossary item such as prednisolone in the 14 days before you start treatment unless you take less than 10mg per day
  • have had a blood transfusion in the last 4 weeks
  • have had a live vaccination Open a glossary item in the last 30 days 
     

Trial design

This is a phase 2 trial. The researchers need 81 people to take part from the UK. It is for people who have chemotherapy before surgery but the cancer doesn’t go away completely.

This trial has 2 parts. Part 1 is looking at treatment for 2 weeks after chemotherapy but before having surgery. 

Part 2 is looking at treatment after surgery for up to a year. This part is for people who have certain gene changes (mutations) in their breast cancer cells. And who have pieces of genetic material in the bloodstream called circulating tumour DNA (ctDNA).

This is a randomised trial. You are put into a treatment group by computer. Neither you nor your doctor can decide which group you are in. 

Treatment after chemotherapy and before surgery (Part 1)
You have 1 of the following:

  • standard care (group A)
  • AZD6738 (group B)
  • olaparib (group C)
  • durvalumab (group D)

In the standard care group you don’t have treatment when you finish chemotherapy. You wait to have your surgery as planned. 

AZD6738 is a tablet. You take them twice a day for 10 days before surgery. 

Olaparib is a tablet. You take them twice a day for 14 days before surgery.

You have durvalumab as a drip into a vein. You have 1 infusion 14 days before surgery. 

The trial doctor can tell you more about exactly when you start and finish treatment.

Everyone then goes on to have their surgery as planned. Your doctor can tell you more about this. 

Treatment after surgery (Part 2)
3 months after surgery you give a blood sample to look for circulating tumour DNA. Researchers know that when breast cancer cells die, they can release small pieces of DNA into the bloodstream. This is called circulating tumour DNA (ctDNA).

You can only join part 2 if you:

  • have ctDNA in your blood
  • have certain changes (mutations) in your breast cancer cells 
  • had treatment in part 1 (you were in group B, C or D)

If you are suitable for part 2, you have the same treatment you had before surgery. You have this for up to 1 year. 

In group B you take AZD6738 tablets twice a day, for 14 days in each 28 day cycle of treatment Open a glossary item

In group C you take olaparib tablets twice a day, every day.

In group D you have durvalumab as a drip into a vein. You have this once a month.

Research samples
You give some extra tissue samples and blood samples if you take part in the trial. The trial team can tell you more about exactly when these are collected.

They plan to use these samples to look for:

  • biomarkers Open a glossary itemthat show if a treatment is working  
  • circulating tumour cells (ctDNA)
     

Hospital visits

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

  • physical examination
  • heart trace (ECG Open a glossary item)
  • blood tests
  • MRI scan 

You have these tests again before you join part 2. And you might also have a:

If you are having AZD6738 or olaparib you take the tablets at home. You go to hospital to have durvalumab, but you shouldn’t need to stay overnight. 

Your doctor can tell you more about breast cancer surgery. And how long you can expect to be in hospital for. 

You have some of the above tests again during and after your treatment. Where possible you have the blood tests at the same time as your routine blood tests.

You see the doctor for regular check ups during treatment. 

You also see them 1 month and 3 months after surgery. 

In part 2 you also see them:

  • when you stop treatment
  • 1 month after finishing treatment
  • 3 months after finishing treatment if you had durvalumab 

Everyone has follow up after trial treatment or surgery every 3 months for up to 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. 

Durvalumab can affect the immune system. It may cause inflammation in different parts of the body which can cause serious side effects. They could happen during treatment, or some months after treatment has finished. Rarely, these side effects could be life threatening.

If you have any of these side effects, you should tell the 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 are:

  • cough
  • diarrhoea
  • tummy pain
  • skin rash or itchy dry skin
  • fever
  • swelling of the legs and ankles or other parts of the body 
  • chest infection
  • difficulty speaking 
  • inflammation of the lungs
  • inflammation of the gut (intestine)
  • liver problems and kidney problems
  • low or high levels of the thyroid hormone 
  • pain or problems passing urine
  • night sweats
  • a sore mouth
  • flu
  • muscle pain
  • a reaction to the infusion causing fever or chills and a change in blood pressure or problems breathing 

The most common side effects of olaparib are:

  • a drop in blood cells causing an increased risk of infection, tiredness, breathlessness and bruising and bleeding
  • tummy pain
  • shortness of breath
  • lack of energy or weakness
  • feeling or being sick
  • diarrhoea
  • indigestion
  • headache
  • taste changes
  • dizziness
  • loss of appetite
  • cough

The most common side effect of AZD6738 is a drop in the number of blood cells causing an increased risk of tiredness, breathlessness, bruising and bleeding. 

There is a risk that  AZD6738 might make you more sensitive to sunlight. So the team advise you to avoid long periods out in the sun, use high factor sunscreen and cover up. 

We have more information about:

Location

Cardiff
London

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

Professor Andrew Tutt

Supported by

AstraZeneca
Institute of Cancer Research 
Cancer Research UK 
 

Freephone 0808 800 4040

Last review date

CRUK internal database number:

16744

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

Harriet wanted to try new treatments

A picture of Harriet

“I was keen to go on a clinical trial. I wanted to try new cancer treatments and hopefully help future generations.”

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