Last year in the UK over 60,000 cancer patients enrolled on clinical trials aimed at improving cancer treatments and making them available to all.
A trial to see the effects of bevacizumab and pazopanib in renal cell cancer
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
The most common type of kidney cancer in adults is renal cell cancer. You may have surgery to remove renal cell cancer. But sometimes it is not possible to remove it with surgery, or the cancer spreads to another part of the body.
In this situation, doctors often use biological therapy including drugs such as bevacizumab and pazopanib. Both of these drugs can stop cancer growing its own blood supply by blocking a body protein called human vascular endothelial growth factor (VEGF).
This type of treatment helps some people, but not others. In this study, doctors want to learn more about what happens to these drugs in your body to see why this is. This is called the pharmacodynamics of the drugs.
The people taking part will have tests to measure the effect of the 2 drugs. The researchers will also collect blood and tissue samples. They use these samples to look for substances that may tell them how well the drugs are working. These are called biomarkers.
Who can enter
You can enter this trial if you
- Have renal cell cancer that is at least partly clear cell type and cannot be removed with surgery
- Have cancer that has got worse despite having treatment in the last 6 months
- Have areas of cancer outside the kidney that can be measured on a scan, and at least one of these areas has not been treated with radiotherapy and is at least 10mm in size
- Are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
- Have recovered from side effects of any other cancer treatment (unless they are very mild)
- Have satisfactory blood test results
- Are willing to use reliable contraception during the trial and for 6 months afterwards if there is any chance you or your partner could become pregnant
- Are at least 18 years old
You cannot enter this trial if you
- Have cancer that has spread to your brain or spinal cord (central nervous system)
- Have already had bevacizumab or pazopanib, or you have had bad reactions to similar drugs
- Have had chemotherapy,
immunotherapyor radiotherapy in the last 4 weeks, apart from radiotherapy for symptoms as long as you have one area of cancer that has not been treated with radiotherapy
- Would not be able to have
biopsiestaken from your cancer because of where it is in your body, or for any other reason
- Have cancer that is affecting the lining of your airways or any large blood vessels in your lungs
- Have had surgery or a serious injury in the last 4 weeks
- Have had another experimental drug in the last 4 weeks (or longer if there is any chance some of the drug could still be in your body)
- Have had any other cancer in the last 5 years, apart from carcinoma in situ of the cervix or non melanoma skin cancer
- Have a wound or broken bone that isn’t healing
- Have problems with bleeding or have coughed up blood in the last 6 weeks
- Take a drug called warfarin to thin your blood – your doctor may be able to change this to another type of blood thinning drug, but it is very important that you don’t stop taking warfarin before talking to your doctor
- Have had a blood clot in the last 6 months unless it was a deep vein thrombosis that has been treated for at least 6 weeks with medication (other than warfarin) that helps to thin your blood
- Have problems with your
digestive system, including anything that could affect you swallowing or absorbing tablets - the trial doctor can advise you about this
- Have ever had a stroke or mini stroke (transient ischemic attack or TIA)
- Have had a heart attack or heart pain (angina) in the last 6 months or have any other heart condition that is a cause for concern - the trial doctor can advise you about this
- Have high blood pressure that cannot be controlled with medication
- Can’t have an MRI scan because you have metal clips, pins or plates in your body, or because you have a pacemaker
- Have ever had a reaction to a dye used during medical tests (contrast medium)
- Have diabetes that is treated with a drug called metformin and the trial doctor thinks it would be unsafe for you not to take it for a day each time you have a PET scan
- Are sensitive to iodine or have ever had asthma
- Are HIV positive
- Have an infection that cannot be controlled with medication or any other condition that the trial doctors think would make it unsafe for you to take part in the trial
- Are pregnant or breastfeeding
The study will recruit at least 12 people who have kidney cancer that has got worse despite having other types of treatment. It is in 2 parts. In part 1, everybody will have bevacizumab.
You have bevacizumab through a drip into a vein every 2 weeks out of 3 for 6 weeks all together.
Two weeks later, you see the study team and they decide if you are likely to benefit from having more treatment that aims to block the cancer’s blood supply. They will also check that you are able to swallow and absorb tablets.
If they think it is appropriate, you go into part 2 of the study. In part 2, you take pazopanib tablets. Because the bevacizumab stays in your bloodstream for several months, you start with a low dose of pazopanib. The dose will be increased slowly as the bevacizumab is cleared from your body.
At this point, you will be put into 1 of 2 treatment groups. Neither you nor your doctor can decide which group you are in. This is called randomisation.
- People in group 1 have pazopanib tablets every day for 3 weeks without a break
- People in group 2 have pazopanib every day for 2 weeks, then have a week off the drug
Each 3 week period is called a cycle of treatment. At the end of each treatment cycle, your pazopanib dose will be increased. The dose can be increased up to 5 times. This is called the dose escalation phase. If you have bad side effects, the study doctor may reduce the dose or delay increasing it.
After 5 dose increases, you go into the maintenance phase. During the maintenance phase, you have a constant dose of pazopanib. As long as you don’t have bad side effects, you can carry on taking it for as long as it helps you.
You will see the study doctors and have a number of tests before you start treatment. The tests include
You will also have a
In the first 8 weeks of treatment, you go to hospital at least 8 times. As well as seeing the study team and having bevacizumab, you have a number of blood tests and scans. You also have another biopsy taken during the second week of treatment.
During the dose escalation phase, you go to hospital and have blood tests once a week. You see the study doctor every 3 weeks and you have a CT scan in the 5th cycle of treatment.
During the maintenance phase, you see the study doctor and have a blood test every 3 weeks. And you have a CT scan every 3 months.
The most common side effects of bevacizumab include
- High blood pressure
- Problems with wound healing
- A drop in blood cells causing an increased risk of infection and bleeding problems
- Tiredness (fatigue)
- Feeling or being sick
- Numbness and tingling in hands and feet
Pazopanib is still quite a new drug and there may be side effects we don’t know about yet. The known side effects include
- Diarrhoea or constipation
- Pain or discomfort in your tummy (abdomen)
- Taste changes and loss of appetite
- Changes to your hair or skin colour
- Changes to how your liver works
- High blood pressure
- Weight loss
- Shortness of breath
The side effects may be worse in the first few weeks of treatment, but the study doctor will try to limit them by starting with a low dose of pazopanib and increasing it gradually.
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.
Professor Tim Eisen
Cambridge University Hospitals NHS Foundation Trust
Experimental Cancer Medicine Centre (ECMC)