A trial of pembrolizumab before surgery and with radiotherapy for head and neck cancer (KEYNOTE 689)

Cancer type:

Head and neck cancers

Laryngeal cancer

Mouth (oral) cancer

Pharyngeal cancer

Secondary cancers

Status:

Open

Phase:

Phase 3

This trial is for people with stage 3 or stage 4a squamous cell carcinoma (SCC) Open a glossary item

of the:

mouth and oropharynx
larynx

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Stage 3 or stage 4a means one of the following:

the cancer is bigger than 4cm but has not spread into any lymph nodes or any other part of the body
the cancer is any size but has spread to one lymph node on the same side of the neck as the cancer. And the lymph node is no more than 3cm across
the cancer has grown through the tissues around the lips and mouth

Everyone taking part is going to have treatment for head and neck cancer for the first time.

More about this trial

Treatment for head and neck cancer, is usually surgery. After surgery, you might have radiotherapy alone or with chemotherapy (chemoradiotherapy). This is to kill any cancer cells that might have been left behind. And lower the risk of the cancer coming back.

But sometimes head and neck cancer comes back after surgery and radiotherapy. This is recurrent disease.

Pembrolizumab (Keytruda) is a type of immunotherapy. It stimulates the body’s immune system Open a glossary item

to fight cancer cells.

Everyone taking part in this trial has one of the following combinations of treatment:

pembrolizumab followed by surgery. After the operation, you have radiotherapy or chemoradiotherapy with pembrolizumab
surgery followed by radiotherapy or chemoradiotherapy

The main aim of this trial is to find out whether pembrolizumab helps people with head and neck cancer.

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 of the following apply:

you have a newly diagnosed squamous cell carcinoma and it is one of the following stages:
- stage 3 cancer of the oropharynx that has tested positive for the human papilloma virus (p16 positive)
- stage 3 or stage 4a cancer of the oropharynx that has tested negative for the human papilloma virus (p16 negative)
- stage 3 or stage 4a cancer of the larynx, hypopharynx or mouth (oral) that has tested positive or negative for the human papilloma virus
you are well enough to have surgery
you have at least one area of cancer that can be seen and measured on a scan
you have a suitable sample of cancer available that doctors can use to test for a biomarker called PD-L1, or you are willing to have a sample taken
if you have oropharyngeal cancer, doctors have tested for the human papilloma virus (or there is a suitable sample of cancer available or you are willing to have a sample taken)
you are well enough to carry out your normal activities, apart from heavy physical work (performance status of 0 or 1)
you have satisfactory blood tests results
you are at least 18 years old
you are willing to use reliable contraception during treatment and for 6 months afterwards if there is any possibility that you or your partner could become pregnant

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related

your doctor can’t find out where the cancer started (cancer of unknown primary)
your cancer has spread from where it started to a distant part of your body (distant metastases)
your cancer started in the space behind the nose (nasal cavity) or in the small spaces close to the nasal cavity (paranasal sinus)
you have had pembrolizumab or any other similar drug
you have had radiotherapy or any other cancer treatment that reached your whole body (systemic)
you have had another cancer in the past 3 years apart from carcinoma in situ of the cervix and breast or non melanoma skin cancer
your cancer has spread to your brain, the tissues surrounding your brain (carcinomatous meningitis) or the spinal cord
you have had severe bleeding from your cancer

Medical conditions

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

are taking part in another clinical trial or have taken part in a trial looking at a new treatment (drug or device) in the past 4 weeks
have taken drugs that damp down your immune system (immunosuppressants) in the past week unless it was a very small dose
have moderate or severe hearing loss
have moderate or severe problems with your nerves that can cause numbness or tingling in fingers and toes
have had a major surgery and still have side effects from it
have had an organ transplant or a bone marrow or stem cell transplant from a donor (allogeneic transplant )
have an autoimmune disease that needed treatment in the past 2 years, apart from treatment to replace something that the body makes such as insulin or thyroxine
have had, or currently have, lung problems such as pneumonitis that needed treatment with steroids
have an infection that needs antibiotics that reach your whole body (systemic)
have HIV
have hepatitis B or hepatitis C
have any other condition or mental health problem that the trial team think could affect you taking part
take an amount of drugs or drink an amount of alcohol that is a concern for your doctors

Other

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

are pregnant or breastfeeding
have had a live vaccine in the past month
are sensitive to any of the drugs used in this trial or anything they contain

Trial design

This is a phase 3 trial. Researchers hope that 24 people from the UK will agree to take part.

It is a randomised trial. Everyone taking part is put into 1 of the following groups by computer:

pembrolizumab, surgery and then radiotherapy (or chemoradiotherapy) and pembrolizumab (group A)
surgery and then radiotherapy or chemoradiotherapy (group B)

Neither you nor your doctor are able to decide which group you are in.

Group A

First, you have 2 pembrolizumab treatments. You have each treatment as a drip into your vein over 30 minutes, every 3 weeks. You then have surgery about 3 weeks after your second pembrolizumab treatment.

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.

After surgery, a specialist doctor called a pathologist looks at the tissue they took during the operation. They check the border of tissue around the tumour for cancer cells. Depending on these results, you join 1 of the following groups:

high risk group
low risk group

You join the high risk group if there are cancer cells close to the border of tissue taken (positive margins). Or if the cancer has spread outside the lymph nodes Open a glossary item

People in the high risk group have the following treatments after surgery:

chemoradiotherapy with a high dose of radiotherapy every weekday, for 6 weeks. And cisplatin as a drip into your vein every 3 weeks, for up to 6 weeks
pembrolizumab as a drip into your vein every 3 weeks, for up 10 months

You join the low risk group if there aren’t cancer cells close to the border of tissue they took (negative margins). And the cancer hasn’t spread outside the lymph nodes.

People in the low risk group have the following treatments after surgery:

a low dose of radiotherapy every weekday, for 6 weeks
pembrolizumab as a drip into your vein every 3 weeks, for up to 10 months

Group B

You have surgery in the same way as if you weren’t taking part in this trial. After surgery, your doctors look at the tissue taken under the microscope. Depending on these results, you join:

the high risk group if there are cancer cells close to the border of tissue taken. Or if the cancer has spread outside the lymph nodes
the low risk group if there aren’t cancer cells close to the border of tissue. And the cancer hasn’t spread outside the lymph nodes

People in the high risk group have a high dose of radiotherapy every weekday, for 6 weeks. And cisplatin as a drip into your vein every 3 weeks, for 6 weeks.

People in the low risk group have a low dose of radiotherapy every weekday, for 6 weeks.

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Blood tests

You have extra blood tests as part of this trial. Researchers want to look for:

certain proteins (biomarkers that can tell how well treatment is working
tumour cells that have broken away from the cancer and are circulating in the blood (circulating tumour cells)

You have the extra blood tests before the start of treatment, at set times during the trial and when you finish treatment.

Tissue sample

If you have oropharyngeal cancer, the trial team will ask to use a tissue sample of cancer they took when you were diagnosed (archival tissue sample). They want to look for the human papilloma virus.

You might need to give a tissue sample (biopsy) if there isn’t a suitable sample available. If you already had the HPV test done, the trial team will check the results before you start treatment.

If you have larynx, hypopharynx or mouth cancer, the trial doctors may also ask you for a tissue sample. They want to look for certain proteins (biomarkers) called PD-L1. You have a biopsy before the start of treatment and if your cancer gets worse.

Quality of life

Everybody taking part completes quality of life questionnaires before the start of treatment and then:

at set times during treatment
after you finish treatment
every 3 months for up to 3 years
then every year for up to 2 years

The questionnaires ask about how you have been feeling and what side effects you have had.

Hospital visits

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

physical examination
a CT scan or MRI scan
a PET-CT scan
heart trace (electrocardiogram )
blood tests
urine tests
hearing test
a camera test to look at the inside of your mouth and throat (nasoendoscopy)

During treatment, you see the trial team regularly. How often you see them depends on the treatment you have. You have blood tests and a physical examination every time you see them.

You have a CT scan or MRI scan before and after surgery. If you join group A, you also have a CT scan or MRI scan at these times:

every 3 months after you finish radiotherapy and for up to 3 years
then every 6 months for up to 2 years

When you finish treatment, you see the trial team after a month. You then see or speak with the trial team:

every 3 months for up to three years
then every 6 months for up to two years

Side effects

The trial team monitor you during treatment and afterwards. You have a phone number to call them if you are worried about anything. The team will tell you about all the possible side effects before you start the treatment.

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:

skin rashes, itching and changes to your skin colour
loose or watery poo (diarrhoea)
cough
pain in your joints, back and tummy (abdomen)
high temperatures
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 more information about the possible side effects of pembrolizumab. And information about the side effects of: