A trial looking at tolinapant and chemoradiotherapy for cervical cancer that has spread (CRAIN)

Cancer type:

Cervical cancer

Status:

Open

Phase:

Phase 1

This trial is looking at adding tolinapant to chemoradiotherapy to improve treatment for cancer of the cervix.     

More about this trial

A usual treatment for cancer of the cervix is a combination of chemotherapy and radiotherapy. This is called chemoradiotherapy. Sometimes the cancer comes back so doctors are looking for ways to improve treatment. In this trial they are looking at a new drug called tolinapant. 

Tolinapant (ASTX660) is a type of targeted cancer drug Open a glossary item called a cancer growth blocker. It blocks certain proteins on cancer cells that help them grow and survive. By blocking this protein it is able to kill and slow down the growth of cancer cells.

This is the first time people with cervical cancer are having tolinapant and chemoradiotherapy. So researchers aren’t sure how well this combination of treatment will work. 

The main aims of the trial are to find out:

  • the best dose of tolinapant to have with chemoradiotherapy 
  • how safe it is to have tolinapant and chemoradiotherapy 
  • what happens to tolinapant in the body 
  • about the side effects of treatment 

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 adenocarcinoma Open a glossary item or squamous cell cancer Open a glossary item of the cervix. Your doctor will know this.
  • have cervical cancer that is stage 1B2 or 1B3, stage 2B or it is stage 3B or stage 3C1. This includes cancer that measures at least 2cm across. The cancer may have spread into tissues around the cervix, grown into the pelvis or be blocking the tubes that drain the kidneys (the ureters). It may also have spread to lymph nodes Open a glossary item in the pelvis but not into the lymph nodes in the tummy (abdomen). 
  • are suitable to have radiotherapy and cisplatin chemotherapy 
  • are fit and active but might not be able to do heavy physical work (performance status 0 or 1)
  • have satisfactory blood test results
  • are willing to use reliable contraception if there is any chance you could become pregnant  
  • are at least 16 years old

Who can’t take part

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

You have had previous treatment for cancer that included:

  • radiotherapy to the pelvis in the past 
  • recent radiotherapy or chemotherapy 
  • recent cancer treatment directly to the skin
  • recent treatment with drugs called monoclonal antibodies Open a glossary item, small molecule drugs or targeted cancer drugs Open a glossary item
  • a type of immunotherapy called CAR T-cell therapy in the last 6 weeks. Your cancer must have got worse after this to take part in this trial. 

As well as the above you cannot join if any of the following apply. You:

  • have cancer that has spread to a distant part of the body 
  • have had an experimental treatment as part of a trial within the last 30 days 
  • have any other cancer that needs treatment 

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

  • have severe liver problems Open a glossary item
  • have HIV or an active hepatitis B or C infection 
  • have had a heart attack or another significant heart problem Open a glossary item that needed treatment in the last 6 months 
  • have a condition that needs steroid treatment unless you are having a low dose. Or you have another treatment that damps down your immune system Open a glossary item within 14 days of having trial treatment.
  • have had major surgery within 30 days of joining the trial 
  • are having medication that affects CYP enzymes 
  • have an active COVID-19 infection when you consent to join the trial 
  • have had major surgery in the last 30 days

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

  • are allergic to tolinapant, anything it contains or any of the other treatments in the trial 
  • have had a live vaccination Open a glossary item within 30 days of joining the trial. You can have the approved COVID-19 vaccines as they aren’t live.
  • are pregnant or breastfeeding

Trial design

This phase 1 trial is taking place in the UK. The team need up to 42 people to take part. 

Everyone has chemoradiotherapy and tolinapant. 

Standard chemoradiotherapy 
You have radiotherapy for 5 weeks. You have this once a day, Monday to Friday. 

You have cisplatin chemotherapy as a drip into a vein. You have this once a week for 5 weeks when you start radiotherapy. 

After chemoradiotherapy you have internal radiotherapy (brachytherapy). This is also part of your routine care. The team will let you know how many sessions you have and when you have this. 

Tolinapant
Tolinapant is a capsule. The number of capsules you take depends on when you join the trial. You start taking them on the same day you start chemoradiotherapy. You take the capsules once a day, every day during:

  • week 1 
  • week 3
  • week 5 

The first few people taking part have a low dose of tolinapant. The next few people have a higher dose if they don’t have any side effects. And so on until you find the best dose to give. This is dose escalation. 

Scans
You have regular scans during the trial. These are part of your routine care. You would have them even if you weren’t taking part in the trial. 

You have an MRI scan Open a glossary item:

  • before starting treatment
  • at week 5
  • during a follow up visit 

Samples for research 
The researchers ask to take an extra sample of cancer tissue (biopsy Open a glossary item). They also ask for some urine samples and extra blood samples. Where possible, you have these blood samples done at the same time as your routine blood tests.

They plan to use the samples to:

  • see what happens to tolinapant in the body 
  • look at genes Open a glossary item to understand more about cervical cancer
  • measure circulating tumour DNA (ctDNA Open a glossary item) in the blood
  • look for substances called biomarkers Open a glossary item to help work out why treatment might work for some people and not for others

You can say no to giving these samples. It won’t affect you taking part in the rest of the trial.

Hospital visits

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

You have chemoradiotherapy at the hospital. You shouldn’t need to stay overnight during the trial. During treatment you see the doctor regularly. This is for blood tests and to see how you are. All these visits are part of your routine care. You won’t have any extra hospital visits if you join the trial. 

Follow up 
After you have your last dose of tolinapant, you see the doctor for a check up at:

  • 6 weeks and then 
  • 12 weeks

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. 

The most common side effects of tolinapant we know about so far include:

This is the first time people with cervical cancer are having tolinapant with chemoradiotherapy. So there may be side effects we don’t know about yet. 

Your doctor will talk to you about all the possible side effects of treatment. You’ll have a chance to ask them any questions you may have. 

We have information about chemoradiotherapy for cervical cancer and the side effects. 
 

Location

Leeds
Manchester
Sheffield
Southampton

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

Professor Peter Hoskin

Supported by

ASTEX Pharmaceuticals
Cancer Research UK Combination Alliance
University Hospital Southampton NHS Foundation Trust
Southampton Clinical Trials Unit
University of Manchester
 

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

19442

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

Charlie took part in a trial to try new treatments

A picture of Charlie

“I think it’s really important that people keep signing up to these type of trials to push research forward.”

Last reviewed:

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