A trial of different types of drugs before surgery for kidney cancer (WIRE)
Cancer type:
Status:
Phase:
This trial is looking at 4 different drugs to have before surgery for kidney cancer. You have them either on their own or in combination.
It is open to people with a type of kidney cancer called clear cell renal cancer who can have surgery to remove it.
More about this trial
The standard treatment for kidney cancer is surgery to remove cancer in the kidney. This might be taking out the whole kidney (nephrectomy) or part of the kidney (partial nephrectomy). Sometimes people have further treatment with cancer drugs after their surgery. You usually don’t have cancer drugs before surgery.
In this trial you will have drugs before surgery. The drugs they are looking at target different parts of cancer cells and can reduce the size of the cancer. You would normally have these drugs for longer than you will in this trial. So the researchers don’t think they will make the cancer smaller. But they think it will give them important information about how they work on the cancer cells. This will help in testing these drugs in future clinical trials.
There are 4 drugs. Depending on when you join this trial you might have 1 of these drugs or a combination of them. The drugs are:
- cediranib
- olaparib
- volrustomig
- rilvegostomig
Cediranib is a cancer growth blocker called a tyrosine kinase inhibitor (TKI). It works by blocking the protein tyrosine kinase that cancer cells need to grow and multiply.
Olaparib is a
Volrustomig is a bispecific
Rilvegostomig is a bispecific monoclonal antibody. It works by blocking the PD-1 and TIGIT proteins on cancer cells. By blocking these proteins, rilvegostomig helps the immune system find and kill the cancer cells.
As a part of the trial you give samples of cancer tissue (
The aim of this trial is to look at these tissue samples and scans to find out if these drugs or combination of drugs might work for kidney 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 had a tissue sample (
biopsy ) showing that you have clear cell renal cancer. If you have not already had a biopsy, you will need to have one taken to be able to join in the trial. - can have surgery to remove all or part of your kidney
- have cancer that measures at least 4cm across. The cancer may or may not have spread to the nearby
lymph nodes or to another part of the body. - have at least 1 area of cancer that can be measured on a scan
- have satisfactory blood test results
- are fully active but might not be able to do heavy physical work (performance status 0 or 1)
- are willing to use contraception during treatment and for 3 months after if there is any chance you or your partner could become pregnant
- are at least 18 years old
Who can’t take part
You cannot join this trial if any of these apply.
Cancer related
You:
- have cancer that has spread to your brain or the tissue covering the brain
- have cancer that is pressing against your spinal cord (
spinal cord compression ) unless it has been successfully treated and there hasn’t been a sign of it getting worse for 28 days before starting trial treatment - have already had similar drugs such as PARP inhibitors,
tyrosine kinase inhibitors ,mTOR inhibitors orimmunotherapy - have had another cancer in the past 2 years apart from cancers that have a low risk of spreading and have been treated with the aim to cure such as
non melanoma skin cancer ,in situ carcinoma of the cervix andprostate cancer where thePSA shows the cancer isn’t growing or early prostate cancer that hasn’t been treated but is being watched closely (active surveillance) - are having other cancer treatment such as chemotherapy. If you have had other cancer treatment it must have finished at least 28 days before starting treatment in this trial.
- can’t have cediranib, olaparib, volrustomig, rilvegostomig or similar drugs
- have ongoing moderate to severe side effects from previous cancer treatment apart from hair loss (alopecia) and white patches on the skin (vitiligo)
- have had a bone marrow transplant from another person (
allogenic transplant ) or a double umbilical blood transfusion
Medical conditions
You cannot join this trial if any of these apply.
- You weigh 30kg (4½st) or less.
- Your body can’t absorb or breakdown certain sugars such as lactose and galactose.
- You have had major surgery within 4 weeks of starting treatment unless you have fully recovered from it. For minor surgery it is 2 weeks.
- You are taking an experimental drug or using an experimental device as part of another clinical trial.
- You are either feeling or being sick and medicines can’t control it.
- You can’t swallow tablets or capsules.
- You have a problem with your
digestive system that affects how well your body absorbs medicines. This includes surgery such as removal of part of the stomach or bowel. - You have a feeding tube such as a
nasogastric tube. - You have had treatment for a
peptic ulcer within 6 months of starting treatment. - You have bleeding in the digestive system within 3 months of starting treatment.
- You had a heart attack or symptoms of congestive heart failure in the past year.
- You had chest pain (angina) that doesn’t have a pattern and can happen when resting in the past year.
- You had heart surgery in the past year.
- You had a blood clot in your arteries in the past year.
- You had a
stroke or mini stroke (TIA) in the past year. - You are taking medication that damps down your
immune system within 28 days of starting treatment apart from inhalers, creams or nasal sprays. If you are taking steroids the dose must be equal to 10mg or less of prednisolone per day. Your doctor will know about this. - You have HIV or any other disease that affects your immune system.
- You have an active infection of tuberculosis (TB), hepatitis B or hepatitis C.
- You have any other medical condition or mental health problem that your doctor or the trial team think will affect you taking part.
Other
You cannot join this trial if any of these apply. You:
- can’t have an
MRI scan . This could be because you have a pacemaker, metal implants, a tube in your heart (coronarystent ) to open a blockage or you are claustrophobic - are pregnant or breastfeeding
There are other reasons why you might not be able to have one of the treatments used in the trial.
Cediranib and olaparib
You cannot have cediranib or olaparib if any of the following apply. You:
- taking medication that affects the CYP enzymes
- have an abnormal heart trace (
ECG ) - are taking medication to correct an irregular heartbeat
- have high blood pressure that is not well controlled
- have signs or symptoms of a blocked bowel within 3 months of starting treatment
- had a collection of puss or infected fluid (abscess) in the tissue of your tummy within 3 months of starting treatment
- have had an abnormal opening (
fistula ) in your gut (digestive system). You might be able to have cediranib and olaparib if you had surgery to repair the opening and there hasn’t been any sign of the opening happening again within the 6 months before starting treatment. - have a heart scan (
ECHO ) that shows your heart isn't pumping blood well enough
Volrustomig and rilvegostomig
You cannot have volrustomig or rilvegostomig if any of the following apply. You:
- weigh more than 35kg (5st 5lb). This applies only to volrustomig.
- had an organ transplant and are taking medication to damp down your immune system
- have a live vaccine within past 30 days. You should not have a live vaccine while having volrustomig or rilvegostomig or within 30 days after the last dose.
- have or had an
autoimmune disease apart from vitiligo - have ongoing moderate to severe side effects from previous cancer treatment. This is apart from hair loss and vitiligo or any other side effect that might not be made worse by volrustomig or rilvegostomig. Your doctor will know about this.
Trial design
This is a phase 2 trial. The team need up to 76 people to join.
You have treatment while you are waiting to have surgery. Depending on when you join the trial you might have one of the following:
- cediranib
- cediranib and olaparib
- olaparib
- volrustomig
- rilvegostomig
Cediranib is a tablet. You take it once a day every day for at least 2 weeks till 36 hours (1½ days) before surgery.
Olaparib is a tablet. You take it twice a day every day for at least 2 weeks until the morning of surgery.
You have a diary to write down when you have your tablets and how many. You must bring this with you when you go to a hospital appointment.
You have volrustomig as a drip into a vein. You have volrustomig over 1 hour. You have only one treatment of volrustomig.
You have rilvegostomig as a drip into a vein. You have rilvegostomig over 60 to 90 minutes. You have only one treatment of rilvegostomig.
Research samples
The research team take a small piece of tissue (biopsy) when you join the trial. This is to confirm that your kidney cancer is a clear cell renal cancer.
You give blood samples and urine samples:
- when you join
- during treatment
- after treatment
Researchers use these samples to find:
- what happens to these drugs in the body
- how these drugs affect the body
- out more about clear cell renal cancer
MRI scan study
The team might ask you to have a scan called a hyperpolarised MRI scan. As part of the scan you have an injection of a
If you are having the hyperploarised MRI scan the team might ask to have another injection of the contrast fluid soon after the first.
By doing another injection and scan they want to show that the results of each are they same.
You don't have to agree to this. You can still take part in the trial.
Hospital visits
You see the doctor to have tests before taking part. These tests include:
- a physical examination
- blood tests
- urine test
- heart trace (
ECG ) - DCE-MRI scan
- CT scan if not done in the month before joining. Your doctor will tell you if you need another CT scan.
- sample of cancer tissue (biopsy)
You see the doctor when you start treatment and 2 weeks later for:
- blood tests
- urine test
- heart trace
After surgery you see the doctor at 6 weeks to see how you are and for:
- blood tests
- urine test
You then see the doctor at 3 months for:
- urine test
- blood tests
- CT scan
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.
Volrustomig and rilvegostomig can affect the These side effects could happen during treatment or months after treatment has finished. Rarely, these side effects could be life threatening. Your doctor or nurse can explain what these side effects are, the risk of them happening and what to look out for. 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 most common side effects of cediranib are:
- high blood pressure
- loss of appetite and weight loss
- diarrhoea
- feeling dizzy
- feeling sick
- headache
- changes to the voice – rough and husky (hoarse)
- itching, rash
- dry or sore mouth
- changes to how the
thyroid works - tiredness and or weakness
- protein in the urine
The most common side effects of olaparib are:
- tummy (abdominal) pain
- changes to blood test results such as the
blood count - cough
- loss of appetite
- diarrhoea
- feeling dizzy
- feeling sick
- headaches
- shortness of breath
- tiredness and or feeling weak
- muscle and joint pain
The most common side effects of volrustomig include:
- a drop in red blood cells causing tiredness and breathlessness
- tummy (abdominal) pain
- changes to how your liver works
- bruising, pain or both at the injection site
- cough
- constipation or diarrhoea
- high temperature (fever)
- difficulty sleeping
- skin problems such as rashes and itching
- lung infections or inflammation
- aching muscles and joints
- feeling or being sick
- shortness of breathing and breathing problems
- changes to how your
thyroid gland works - tiredness (fatigue), weakness or both
The most common side effects of rilvegostomig include:
- cough
- loss of appetite
- aching muscles and joints
- tiredness (fatigue), weakness or both
We have information about olaparib and its side effects.
Your doctor or a member of the trial team will talk to you about the possible side effects of the treatments before you agree to take part.
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 Grant Stewart
Supported by
Cambridge University Foundation Hospital Trust
University of Cambridge
AstraZeneca
Cancer Research UK Cambridge Centre
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040