A trial of pembrolizumab, chemotherapy and hormone therapy for breast cancer (KEYNOTE-756)

Cancer type:

Breast cancer

Status:

Open

Phase:

Phase 3

This trial is looking at adding a drug called pembrolizumab to chemotherapy and hormone therapy for newly diagnosed breast cancer.

It is for people whose cancer is HER2 negative and oestrogen (ER) positive. This means the breast cancer cells:

don’t have receptors for HER2
do have receptors for oestrogen

More about this trial

You might have surgery for breast cancer. Sometimes you have chemotherapy before surgery. This is called neo adjuvant chemotherapy. It can shrink the cancer and make the surgery more successful.

Some people have a higher risk of the cancer coming back afterwards. So, you might also have treatment after surgery such as hormone therapy Open a glossary item . This is to keep the cancer under control for longer.

Chemotherapy, surgery and hormone therapy are all usual or standard treatments Open a glossary item for breast cancer. Researchers are looking for ways to improve treatment. In this trial, they are looking at adding a drug called pembrolizumab. It is a type of immunotherapy. It stimulates the body’s immune system to fight cancer cells.

In this trial, everyone has surgery, chemotherapy and hormone therapy. And some people have pembrolizumab and some don’t.

The main aims of the trial are to:

find out if adding pembrolizumab to usual treatment improves treatment for breast cancer
learn more about the side effects

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 join this trial if all the following apply.

You:

have newly diagnosed breast cancer
have a type of invasive breast cancer called ductal breast cancer that is bigger than 2cm across. You may also have cancer cells in the lymph nodes in the armpit or in the lymph nodes behind the breast bone but not in both areas.
have oestrogen receptor positive breast cancer
have no or low amounts of a protein called HER2 (HER2 negative breast cancer)
have a recent tissue sample available for the trial team to do some tests on or you are willing to give a new sample
are well enough to be up and about for at least half the day (performance status 0 or 1 )
have satisfactory blood test results
are willing to use reliable contraception during treatment and for 6 months afterwards or for 12 months afterwards if you have cyclophosphamide if there is any chance you or your partner could become pregnant
are at least 18 years old

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related.

You:

have a type of breast cancer called lobular invasive breast cancer
have cancer that has spread to the lymph nodes further away than the armpit such as under the collarbones
have cancer that has spread elsewhere in the body
have breast cancer that is fast growing (grade 3 breast cancer)
have cancer in both breasts
have more than 1 area of breast cancer that is in different areas of the breast
have cancer that is ER negative
have already had treatment for breast cancer
have had surgery to remove the cancer and or the lymph nodes or you have had a sentinel node biopsy before starting trial treatment
have had pembrolizumab or a similar drug
have had another other cancer in the last 5 years that is getting worse or needs treatment
have had another treatment or used a device as part of a clinical trial within 4 weeks of starting treatment

Medical conditions
You:

have a problem with your immune system or you are having more than 10mg of steroids a day or any other treatments to dampen down the immune system within 7 days of the starting trial treatment
have an active autoimmune condition and you needed treatment to the whole body (systemic treatment) in the last 2 years
have or have had a lung condition such as pneumonitis that needed steroid treatment
have had tuberculosis (TB) in the past
have an active infection that needs treatment
have problems with your heart such as a heart attack in the last 6 months, congestive heart failure or the left side of your heart doesn't work very well
have HIV
have had hepatitis B or you have an active hepatitis C infection
have any other medical condition or mental health problem that the trial team think would affect you taking part

Other
You:

are pregnant or breastfeeding
have had a live vaccination in the 30 days before starting trial treatment
are allergic to any of the treatments in the trial

Trial design

This is a phase 3 trial. The researchers need 1,140 people to take part including 32 from the UK.

It is a randomised trial. You are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in. And neither you nor your doctor will know which treatment you are having. This is a double blind trial.

You have 1 of the following:

pembrolizumab and usual treatment (group A)
a dummy drug (placebo ) and usual treatment (group B)

People in group A have treatment as follows:

chemotherapy and pembrolizumab
then more chemotherapy and pembrolizumab
then surgery
then hormone therapy and pembrolizumab

People in group B have treatment as follows:

chemotherapy and a dummy drug
then more chemotherapy and a dummy drug
then surgery
then hormone therapy and a dummy drug

You are put into 1 of the following groups at random:

16042_keynote_756.png

Chemotherapy with pembrolizumab or the dummy drug
First, you have 4 treatment cycles of chemotherapy and pembrolizumab or the dummy drug.

Each treatment cycle takes 21 days (3 weeks). You have each cycle in the following way:

pembrolizumab or the dummy drug as a drip into a vein on day 1
paclitaxel as a drip into a vein on day 1, day 8 and day 15

Then you have 4 more cycles of chemotherapy and pembrolizumab or the dummy drug.

You have:

pembrolizumab or the dummy drug as a drip into a vein on day 1
doxorubicin or epirubicin as a drip into a vein on day 1
cyclophosphamide as a drip into a vein on day 1

Some people might have treatment in 2 week rather than 3 week cycles. Your doctor will tell you if this applies and how often you have treatment.

Surgery
About 3 to 6 weeks after you finish chemotherapy, you have surgery. You have surgery in the same way as if you weren’t taking part in this trial. Your doctor can tell you more about this and what to expect.

Hormone therapy with pembrolizumab or the dummy drug
About 4 weeks after your surgery, you have pembrolizumab or the dummy drug. This is followed by the hormone therapy.

You have 9 cycles of pembrolizumab or the dummy drug. You have this on day 1 of each treatment cycle.

You have hormone therapy for up to 10 years. You might have a drug called tamoxifen or a type of drug called an aromatase inhibitor Open a glossary item . Your doctor will tell you:

which type you have
when you start it
how often you have it

Some people might also have radiotherapy. Your doctor will tell you how often you will have it and for how long.

You stop treatment if your cancer gets worse. Your doctor will talk to you about other treatment options.

Quality of life
The trial team will ask you to fill out 3 questionnaires before you start treatment and at set times during treatment. You use an electronic tablet to do this. The questionnaires will ask about side effects and how you’ve been feeling. This is called a quality of life Open a glossary item study.

Samples for research
You give some extra blood samples during treatment. You give the samples at specific times and the trial team will give you more information about this. They plan to use the samples to:

see how well treatment is working
find out what happens to the drugs in the body
look for biomarkers to predict who will benefit from treatment

MRI sub study
About 150 people have MRIs of the breast. They have this:

before the trial starts
before surgery

You don’t have to agree to join this part of the trial if you don’t want to.

Hospital visits

You see a doctor and have some tests before you can take part. These include:

physical examination
blood samples
urine samples
heart trace (ECG )
heart scan (ECHO or MUGA )

You see the doctor regularly through treatment:

for blood tests
a physical examination
to see how you are

Follow up
When you finish treatment the trial team follow you up for about 12 years to see how you are getting on.

This happens:

every 3 months for the first 3 years
every 6 months in the 4th and 5th year
once a year after that

Side effects

As pembrolizumab is a new drug for breast cancer, there may be some side effects we don’t know about yet. The trial team will monitor you during the time you have treatment and you’ll have a phone number to call if you are worried about anything.

Pembrolizumab has an effect on the immune system. This may cause inflammation in different parts of the body which can cause serious side effects.

These side effects could happen during treatment, or some months after treatment has finished. In some people, these side effects could be life threatening.

The most common side effects of pembrolizumab are:

itchy skin, skin rash and loss of skin colour
diarrhoea
cough
joint and back pain
fever
pain in your tummy (abdomen)
thyroid problems that can cause tiredness and feeling cold
low levels of salt in your body that may cause you to feel tired, have headaches and muscle cramps

We have information about the side effects of:

The trial doctors will explain all the possible side effects before you join the trial.

Location

Birmingham

Bristol

Colchester

London

Nottingham

Truro

Recruitment start:

05/02/2019

Recruitment end:

04/01/2031

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.

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

Chief Investigator

Professor Peter Schmid

Supported by

Merck, Sharp & Dohme

Freephone 0808 800 4040

Email

Last review date

1 April 2022

CRUK internal database number:

16042