A trial of chemoradiotherapy with or without pembrolizumab for cervical cancer (KEYNOTE-A18)

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

Cancer type:

Cervical cancer

Status:

Closed

Phase:

Phase 3

This trial is looking at pembrolizumab for cervical cancer that has spread into the surrounding tissue (locally advanced) and has a high risk of coming back.

More about this trial

Chemotherapy with radiotherapy (chemoradiotherapy) is one of the standard treatments for locally advanced cervical cancer.  

Pembrolizumab is an immunotherapy Open a glossary item. It works by helping the immune system Open a glossary item kill cancer cells. 

We know from research that adding pembrolizumab to chemoradiotherapy can help people with other types of cancers. Researchers think that it could also help people with cervical cancer. 

In this trial researchers will compare having chemoradiotherapy with pembrolizumab to chemoradiotherapy with a dummy drug (placebo Open a glossary item). 

The aims of the trial are to find out how:

  • safe it is to give pembrolizumab with chemoradiotherapy
  • well it works 
  • it affects quality of life Open a glossary item
  • well pembrolizumab with chemoradiotherapy is accepted in the body

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 cervical cancer that is at least 2cm, has grown into the vagina or the surrounding tissue (stage 1B2 to 2B). And has spread to the lymph nodes Open a glossary item. Or if you have either lymph node spread or bowel spread or bladder spread (stage 3 to 4A).
  • have squamous cell cancer, adenocarcinoma or adenosquamous carcinoma type of cervical cancer   
  • have an area of cancer that the doctor can see on a scan Open a glossary item
  • have a tissue sample (biopsy Open a glossary item) that the trial team can ask for. If not you must be willing to have a fresh biopsy taken. 
  • can look after yourself but might not be able to do heavy physical work (performance status 0 or 1)
  • have satisfactory blood test results
  • and your partner are willing to use reliable contraception during treatment and for a time after if there is any chance you might get pregnant
  • are at least 18 years old

Who can’t take part

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

  • have cancer that has spread to organs far away from the cervix such as the lungs (stage 4B
  • are having your womb removed (hysterectomy) or part of it as of your cancer treatment. You might be able to join if you have had a previous hysterectomy that was not part of your cancer treatment.
  • can't have internal radiotherapy (brachytherapy) Open a glossary item
  • have had previous immunotherapy  Open a glossary itemtreatment
  • have had previous cancer treatment that reaches your whole body such as chemotherapy within 4 weeks of being put into a trial treatment group (randomisation Open a glossary item)
  • have had an experimental drug as part of another clinical trial within 4 weeks of randomisation
  • 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 Open a glossary item and any in situ carcinoma. Open a glossary item 

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

  • have a kidney problem where both kidneys are swollen because of too much urine in them. You might be able to join if you have had one of your kidneys treated for this such as by putting in a tube to help drain the urine. 
  • have had drugs that stimulate the immune system within 6 weeks of starting treatment
  • can’t have the chemotherapy drug cisplatin
  • have an immune system Open a glossary item that isn’t working very well 
  • are taking steroids within a week of starting treatment. Unless it is a small dose. Your doctor will know what the dose is.
  • are taking any other medication that affects how well the immune system works within a week of starting treatment
  • have an autoimmune disease Open a glossary item that has needed treatment in the past 2 years. This is apart from creams, inhalers or medication to replace a substance the body usually makes. 
  • have inflammation of the lungs or had inflammation of the lungs that needed treatment with steroids
  • have an active infection that needs treatment
  • have HIV, hepatitis B or hepatitis C
  • have had a stem cell transplant from someone else (allogeneic transplant)
  • have had an organ transplant
  • have any other medical condition or mental health problem that the doctor or the trial team think could affect you taking part

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

  • are allergic or sensitive to pembrolizumab or any of its ingredients
  • have a live vaccine Open a glossary item within 30 days of starting treatment in the trial
  • are pregnant or breastfeeding

Trial design

This is an international phase 3 trial. The trial team need about 980 women worldwide to take part with 6 people from the UK.

This is a randomised double blind trial. You go into 1 of 2 treatment groups. Neither you nor your doctor can choose which group you are in. And neither you nor your doctor will know which treatment you have. During the trial your doctor will be able to find out which treatment you are having if they need to. 

The groups are:

  • chemoradiotherapy with pembrolizumab followed by pembrolizumab on its own
  • chemoradiotherapy with a dummy drug (placebo) followed by the dummy drug on its own

Chemoradiotherapy 
Chemoradiotherapy is having chemotherapy at the same time as having radiotherapy. 

The chemotherapy you have is cisplatin. You have cisplatin as a drip into a vein. You have cisplatin once a week for 5 weeks. You might have another week of cisplatin. Your doctor will tell you if you are going to have this. 

You have external radiotherapy once a day Monday to Friday for 5 weeks. Before starting radiotherapy you have a planning appointment. This is so the doctor and the radiographer can work out where to give the radiotherapy and how much to give. 

After external radiotherapy you have internal radiotherapy (brachytherapy). You can have brachytherapy in the hospital as an inpatient. Or you might have it as an outpatient in the radiotherapy department. Your doctor will talk to you about this. And about how many treatments you have. 

For brachytherapy you have a radioactive applicator put into your vagina and cervix. This delivers radiotherapy to the cancer and very little to the surrounding tissue. When the applicator is in you need to lie flat on your back and still. 

Pembrolizumab or the dummy drug
You have pembrolizumab or the dummy drug the same way. You have it as a drip into a vein. During chemoradiotherapy you have it once every 3 weeks. Each 3 week period is a cycle of treatment Open a glossary item. You have 5 cycles of treatment.

After chemoradiotherapy each cycle of treatment is once every 6 weeks. You have 15 cycles of treatment. 

Quality of life
You fill in a few questionnaires at the start of treatment and then:

  • at the start of each cycle of treatment
  • when you finish treatment and then
  • every 3 months for 2 years
  • every 6 months for a year and then 
  • every year

The questions ask about:

  • your general health
  • what daily activities you can do
  • side effects
  • symptoms

These are quality of life questionnaires

Research samples
You give blood samples during treatment. 

The trial team will also ask for a piece of the sample tissue (biopsy) from a previous sample. If this is not available you must be willing to have a fresh biopsy taken. 

Researchers will use these samples to:

  • look for substances (biomarkers Open a glossary item) that might tell them how well treatment is working
  • find out what happens to pembrolizumab in the body
  • find out how pembrolizumab affects the body
  • find out more about cervical cancer  

Hospital visits

You see the doctor for tests before taking part. These tests include:

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

3 months after finishing chemoradiotherapy you have a:

  • PET-CT scan
  • CT scan
  • MRI scan

After treatment you see the doctor every 3 months for 2 years and then:

  • every 6 months for a year
  • and then every year until you start another treatment or your cancer gets worse

You have a CT scan and an MRI scan every time you see the doctor. You might have an extra scan if one of the scans shows your cancer might be getting worse. If this happens your doctor will talk to you about whether you should continue having treatment or not. 

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.

Pembrolizumab 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 common side effects of pembrolizumab are:

  • skin problems such as itching, a rash and loss of colour
  • diarrhoea
  • cough
  • joint and back pain
  • tummy (abdominal) pain
  • high temperature (fever)
  • the thyroid gland not making enough hormones causing feeling tired, weight gain, feeling cold or constipation
  • low levels of salt in the blood causing feeling tired, feeling confused, headaches, muscle cramps, feeling sick or being sick 

We have more information about pembrolizumab

We have information about the side effects of:

Your doctor or a member of the trial team will talk to you about the possible side effects of all the treatments before you agree to take part.

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

Dr Susan Lalondrelle

Supported by

Merck, Sharp & Dohme LLC

Freephone 0808 800 4040

Last review date

CRUK internal database number:

17441

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

Around 1 in 5 people take part in clinical trials

3 phases of trials

Around 1 in 5 people diagnosed with cancer in the UK take part in a clinical trial.

Last reviewed:

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