A trial of nivolumab before and after surgery for breast cancer (CheckMate 7FL)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Breast cancer

Status:

Closed

Phase:

Phase 3

This trial is looking at adding nivolumab to chemotherapy and comparing it to chemotherapy alone before surgery. It is also looking at adding nivolumab to hormone therapy and comparing it to hormone therapy alone after surgery.

It is open to people who have newly diagnosed breast cancer. And who have cancer that:

has large amounts of hormone receptors (ER positive cancer ) and
a small number of receptors for HER2 (HER2 negative cancer)

More about this trial

Chemotherapy, surgery and hormone therapy are all usual or standard treatments for breast cancer. Doctors are looking for ways to improve treatment for invasive ductal breast cancer. In this trial they are looking at:

adding nivolumab to standard chemotherapy before surgery
adding nivolumab to standard hormone therapy after surgery

Nivolumab is a type of cancer treatment called an immunotherapy. It helps your immune system Open a glossary item to find and kill cancer cells.

The main aims of this trial are to find out:

how well nivolumab works
how safe it is to have nivolumab with chemotherapy before surgery and alongside hormone therapy after surgery
more about the side effects

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.

Who can take part

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

have invasive breast cancer that measures more than 1cm across. The doctor checks if you have cancer in the nearby lymph nodes . You may also be able to take part if you have inflammatory breast cancer.
have cancer that has large amounts of hormone receptors. This is oestrogen receptor positive breast cancer .
have cancer that has small amounts of HER2 proteins. This is HER2 negative breast cancer.
have cancer that your doctor can see and measure on a scan
have medium to high grade cancer (grade 2 or grade 3)
are suitable to have chemotherapy before surgery
are suitable and willing to have surgery for breast cancer
can swallow tablets
have a sample of tissue (biopsy) available for the trial team to do some tests on or you are willing to give a new sample. You are also willing to give a sample when you have surgery.
have a tissue sample that shows if your cancer has the PD-L1 protein
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 active but might not be able to do heavy physical work (performance status 0 or 1)
have satisfactory blood test results
are at least 18 years old

Who can’t take part

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

can’t have surgery for breast cancer
have cancer that has spread elsewhere in the body
have more than one area of cancer in the same breast or you have cancer in both breasts
had ductal carcinoma insitu (DCIS ) on the same side of the body and you had radiotherapy
have had DCIS in the past unless there have been no signs of it for at least 2 years
have a type of lobular carcinoma insitu (LCIS ) called pleomorphic lobular carcinoma unless you have had surgery and it was more than 5 years ago
have already had surgery to remove the breast cancer or lymph nodes under the armpit. Or you have had a sentinel node biopsy done before you start trial treatment.
have cancer in the lymph nodes above or below the collarbone, in the armpit or the breastbone. This is lymph node stage cN3. Your doctor can tell you more about this.
have already had treatment for your recently diagnosed breast cancer. This includes chemotherapy, hormone treatment, a targeted drug or radiotherapy.
have had immunotherapy or another similar drug in the past
have breast cancer that your doctor thinks should be treated with hormone therapy before surgery
have had another cancer that has got worse or needed treatment in the past 3 years. This is apart from successfully treated non melanoma skin cancer , carcinoma in situ (CIS ) of the cervix, prostate, or breast or early bladder cancer.

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

have had a heart attack in the last 6 months or a significant heart problem that needs treatment. The trial team check if you have a heart condition before you join the trial.
have interstitial lung disease, scarring on the lungs or active inflammation of the lungs (pneumonitis )
have or have had inflammation of the heart muscle (myocarditis)
have an autoimmune condition that needs treatment apart from certain ones. Your doctor will know about this.
have HIV and AIDS. You may be able to take part if you have HIV. The trial team can talk to you about this.
have an active hepatitis B or hepatitis C infection or you have another active infection that needs long term antibiotics
have had treatment that damps down the immune system . This includes steroids within 2 weeks of starting trial treatments unless it was a low dose.
have any other serious or uncontrolled medical condition
have a problem with your digestive system that means you won’t be able to absorb medication
are having HRT , hormonal contraception or any other medication that contains oestrogen . You may be able to take part if you can stop this medication before you start trial treatment.
have any other medical condition or mental health problem that the trial team think could affect you taking part

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

are allergic to nivolumab or anything it contains
have had a live vaccine within 30 days of starting trial treatment. The current approved COVID-19 vaccines are not live.
have had herbal supplements or traditional Chinese medicines to treat your cancer within 2 weeks of starting trial treatment
are breastfeeding, pregnant or planning a pregnancy

Trial design

This phase 3 trial is taking place worldwide. The team need 1,200 people to take part including 36 from the UK.

It is a randomised trial. You are put into a treatment group by a computer. Neither you nor your doctor will be able to decide which group you are in.

You have 1 of the following:

standard treatment and nivolumab (Group A)
standard treatment and a dummy drug (placebo ) (Group B)

Diagram 1

Before surgery you have:

standard chemotherapy and nivolumab (Group A) or
standard chemotherapy and a dummy drug (Group B)

After surgery you have:

standard hormone treatment and nivolumab (Group A) or
standard hormone treatment and a dummy drug (Group B)

If you are in the nivolumab group (group A) before surgery you also have nivolumab after surgery.

Flow Chart 1

You have nivolumab, the dummy drug and chemotherapy as a drip into a vein. You have hormone treatment as tablets.

Treatment before surgery
This treatment period takes about 5 to 6 months.

For the first 12 weeks you have:

nivolumab or the dummy drug once every 3 weeks
a chemotherapy drug called paclitaxel once a week

You then have treatment as follows until this treatment period finishes. You have:

nivolumab or the dummy drug once every 2 or 3 weeks
doxorubicin or epirubicin once every 2 or 3 weeks
cyclophosphamide once every 2 or 3 weeks

Your doctor decides if you have treatment on the 2 or 3 week schedule.

Surgery
The team then check if you are well enough to have your surgery as planned. You have surgery about 4 weeks after you finish chemotherapy. Your surgeon or doctor can tell you more about the type of surgery and what it involves. You can ask them any questions you may have.

Treatment after surgery
1 to 2 weeks after surgery you have a check up at the hospital. You begin further treatment when you are well enough. The trial team can tell you when this starts.

This treatment period takes about 7 months.
You have:

nivolumab or the dummy drug once every 4 weeks for 28 weeks
hormone therapy tablets every day

You have one of the following hormone treatments:

The trial team can tell you how many tablets to take.

You may continue to have the same hormone therapy for up to 10 years. Your doctor may decide to change the hormone therapy you are having. The trial team can tell you more about this.

Follow up
When you finish treatment you see the trial doctor:

1 month later for a check up
about 3 months after your last dose of nivolumab or the dummy drug

The trial team then call you to see how you are or you see them at a routine check up:

every 3 months for up to 2 years and then
every 6 months for 5 years and then
once a year for 3 years

Samples for research
The researchers ask you to give some extra tissue samples. They also ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests.

They plan to use the samples to:

look at genes on the cancer cells to understand more about breast cancer
look for substances called biomarkers to help work out why treatment might work for some people and not for others

Quality of life
The trial team ask you to fill out an electronic questionnaire:

before you start treatment
at set times during and after treatment

The questionnaire asks about side effects and how you’ve been feeling. This is called a quality of life study

Hospital visits

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

blood tests
a physical examination
heart trace (ECG )
heart scan (echocardiogram ) or MUGA scan
a breast ultrasound , mammogram or an MRI of your breast. These tests are repeated when you finish the treatment you have before surgery. You might have them again after surgery

You might also need to have a CT scan or MRI scan.

You have nivolumab, the dummy drug and chemotherapy on the day ward.

You see the doctor regularly during treatment to see how you are and for blood tests.

If you have remaining breast cancer tissue you have:

a mammogram after surgery and then
once a year

You continue to have mammograms of the breast that wasn’t affected by cancer. You have these according to routine guidelines in your area.

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.

Nivolumab can affect the immune system. It may cause inflammation in different parts of the body. This 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 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 nivolumab are: