A trial of nivolumab, ipilimumab and chemotherapy for oesophageal cancer (CheckMate 648)

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

Cancer type:

Oesophageal cancer

Status:

Closed

Phase:

Phase 3

This trial is for people with advanced cancer of the food pipe (oesophageal cancer). It is open to people with:

cancer that has come back (recurrent cancer)
advanced cancer that can’t be removed with surgery
cancer that has spread elsewhere in the body (metastatic cancer)

More about this trial

Chemotherapy is a common treatment for advanced oesophageal cancer. But it may continue to grow despite this treatment. So doctors want to improve treatment for people in this situation.

In this trial, they are looking at 2 drugs called nivolumab and ipilimumab. They are both types of immunotherapy. They work in slightly different ways.

Nivolumab blocks a protein called PD L1 on the surface of immune cells. Blocking this protein triggers the immune system to find and kill cancer cells.

Ipilimumab works by attaching itself to normal immune cells. This changes the way these cells work and helps the immune system destroy cancer cells.

But researchers aren’t sure if these treatments will work better than standard chemotherapy, such as fluorouracil (5FU) and cisplatin. So they want to compare them to find out more.

The aims of this trial are to find out:

if having immunotherapy works better than chemotherapy
if having immunotherapy and chemotherapy works better than chemotherapy alone
how safe the treatment is
more about quality of life
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 squamous cell cancer or a mix of squamous cell cancer and adenocarcinoma (adenosquamous) cancer of the food pipe (oesophagus)
have advanced cancer that can’t be removed with surgery, cancer that has come back or cancer that has spread elsewhere in the body
have cancer that the doctor can measure on a scan
have a sample of tissue (biopsy) available that the trial team can do some tests on or you are willing to give a new sample
are well enough to carry out all your normal activities, apart from heavy physical work (performance status 0 or 1)
are willing to use reliable contraception during the trial and for up to 7 months afterwards
have satisfactory blood test results

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related

You:

have cancer that is a type called adenocarcinoma
are suitable to have treatment such as chemoradiotherapy or surgery with the aim to cure
have already had treatment for advanced cancer that can’t be removed with surgery, cancer that has come back or cancer that has spread elsewhere in the body
have cancer that has spread to the brain and is causing symptoms or needs treatment – you might be able to take part if you don’t have symptoms or it has been successfully treated
have a high risk of bleeding or developing a fistula because the tumour has grown into nearby organs such as the main artery in the heart (aorta) or the windpipe (trachea)
have pain from your tumour that isn’t controlled
have had nivolumab, ipilimumab or any other similar drug in the past

Medical conditions:

You:

haven’t fully recovered from major surgery or a very bad injury
have side effects from past treatment unless they are mild apart from hair loss or tiredness (fatigue)
have an active infection that means you can’t take part in the trial
are poorly nourished (have malnutrition)
have a condition called interstitial lung disease that is causing symptoms
have numbness or tingling in your hands or feet (peripheral neuropathy) unless this is mild
have an autoimmune disease unless it is vitiligo, type 1 diabetes, hair loss (alopecia), thyroid problems that are controlled by medications or a skin condition called psoriasis that doesn’t need treatment
you take steroids or other drugs that dampen down the immune system unless they are creams, inhalers or you take a stable dose of adrenal replacement hormone
have HIV or AIDS
have hepatitis B or hepatitis C
have any other serious condition or mental health problem that the trial team think could affect you taking part

Other:

you are allergic or sensitive to anything the trial drugs contain
there is any reason you can’t have the chemotherapy drugs fluorouracil or cisplatin
you are pregnant or breastfeeding

Trial design

This is a phase 3 trial. The researchers hope 939 people will take part worldwide including 12 from the UK. It is a randomised trial. You are put into 1 of the following treatment groups by computer:

nivolumab and ipilimumab
nivolumab and chemotherapy
chemotherapy

You have all your treatment as a drip into a vein. Depending on which group you are in, you have treatment for up to 2 years. You have it for as long as it is working and the side effects aren’t too bad.

Nivolumab and ipilimumab group

You have treatment in cycles. Each 2 week period is a cycle of treatment. You have:

nivolumab every 2 weeks
ipilimumab every 6 weeks

Nivolumab and chemotherapy group

Each 4 week period is a cycle of treatment. Day 1 is the first day of each treatment cycle. You have:

nivolumab on day 1 and day 15
fluorouracil on day 1 to 5 through a small hand held pump
cisplatin on day 1

Chemotherapy group

Each 4 week period is a cycle of treatment. You have:

fluorouracil from day 1 to day 5 through a small hand held pump
cisplatin on day 1

Quality of life

The trial team will ask you to fill out questionnaires before you start treatment and at set times during treatment. The questionnaires will ask about side effects and how you’ve been feeling. This is called a quality of life study.

Samples for research

The trial team will ask you to give some extra blood samples. Where possible you have these at the same time as your routine samples.

They will ask to look at a sample of tissue you gave when you were first diagnosed.

The researchers plan to look at:

biomarkers
what happens to the drugs in your body
genes

They might also ask you to give a new sample if your cancer gets worse. But you don’t have to agree to give this if you don’t want to. You can still take part in the trial.

Hospital visits

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

a physical examination
heart trace (ECG)
blood tests
urine tests
CT scan or MRI scan

You might also have a CT or MRI scan of your brain.

You have treatment at the hospital. How often you go depends on which treatment group you are in. At each visit, you see the trial doctor for a check up and blood tests.

You have a CT or MRI scan every: