A trial looking at tolinapant and chemoradiotherapy for cervical cancer that has spread (CRAIN)
Cancer type:
Status:
Phase:
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 
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 or squamous cell cancer of the cervix. Your doctor will know this. - have cervical cancer that is stage 1B2 or 1B3, it is stage 2 or it is stage 3A, 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 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 , small molecule drugs or targeted cancer drugs - 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 - have HIV or an active hepatitis B or C infection
- have had a heart attack or another significant
heart problem 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 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 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 :
- 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 (). 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 to understand more about cervical cancer - measure circulating tumour DNA (
ctDNA ) in the blood - look for substances called
biomarkers 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:
- blood tests
- urine tests
- a
physical examination - heart trace (ECG)
- heart scan (echocardiogram)
- CT scan or PET-CT scan
- MRI scan
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:
- an increased risk of feeling tired, breathless and looking pale (
anaemia ) - feeling or being sick
- skin rash
- changes to how your pancreas is working
- liver changes
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
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.
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
