A trial of cediranib and saracatanib for kidney cancer that has spread to other parts of the body (COSAK)

Who can enter

You can enter this trial if you

• Have renal cell cancer that is at least partly clear cell type and has spread
• Have areas of cancer outside the kidney that can be measured on a scan, and one area of cancer is at least 10mm in size
• Have already had treatment that targeted VEGF such as pazopanib, sunitinib (Sutent), sorafenib (Nexavar) or bevacizumab (Avastin)
• Have satisfactory blood test results
• Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
• Are willing to use a reliable form of contraception during the trial and for 2 weeks afterwards if you are a man, or a month afterwards if you are a woman, 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 (you may be able to take part if you have had treatment for cancer that has spread to your brain, as long as you don’t have any symptoms and your doctors can see on a scan that it hasn’t got worse in 10 days or more after you stopped taking steroids)
• Are currently having any other anti cancer treatment apart from steroids
• Have had other drug treatment for your cancer in the last 2 weeks (4 weeks if you had a combination of bevacizumab and interferon)
• Have had radiotherapy in the last 2 weeks
• Have had major surgery in the last 2 weeks or earlier if the scar has not completely healed up
• Have not recovered from the side effects of other treatment, unless they are very mild - you can take part if you still have hair loss or a drop in the level of thyroid hormones (hypothyroidism)
• Have ever had a bone marrow transplant
• Have had an experimental drug as part of another clinical trial in the last month (apart from drugs targeting VEGF)
• Have had another type of cancer in the last 5 years apart from non melanoma skin cancer, carcinoma in situ, prostate cancer that was contained within the prostate gland and has been treated, or any other cancer if you have been completely free of the disease for at least 2 years
• Have had severe bleeding in the last 3 months, or have coughed up more than a teaspoonful of blood in the last 4 weeks
• Have had a heart attack or heart surgery in the last 6 months, or have another heart condition that is a cause for concern
• Have high blood pressure that cannot be controlled with medication or you need to take very high doses of drugs to control it
• Have a lot of protein in your urine
• Have any problems with your digestive system that could affect how you absorb tablets
• Have any other serious medical condition that the trial doctors think could affect you taking part in this trial
• Are known to be HIV, hepatitis B hepatitis C positive, or have a lowered immunity
• Are pregnant or breastfeeding

Trial design

This is a phase 2 trial. It will recruit about 130 people across the UK. It is a randomised trial. The people taking part are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in. And you will not know which group you are in. This is called a double blind trial.

• People in group 1 take a cediranib tablet and 2 saracatanib tablets once a day
• People in group 2 take a cediranib tablet and 2 dummy tablets (placebos)

As long as you are not having too many side effects, you can carry on having the treatment for as long as it helps you.

The trial team will ask your permission to get a sample of tissue removed when you had a biopsy to diagnose your cancer. They may also take some extra blood samples during the trial. And depending on where in your body the cancer has spread to, they may ask to take another biopsy. They will use these samples to learn more about how genes affect the way people respond to these drugs. And they will learn more about what happens to the drug in the body.

The researchers may also ask you to have 2 extra scans called FDG-PET scans. You would have one before you start treatment and the other 4 weeks later.

If you don’t want to give these extra samples for research, or have the extra scans, you don’t have to. You can still take part in the trial.

Hospital visits

You will see the trial doctors and have some tests before you start treatment. The tests include

• Physical examination
• Blood tests
• CT scan or MRI scan
• Heart trace (ECG)

You go to see the trial doctors every 2 weeks for the first month of treatment and then every 4 weeks after that. You have blood tests at each visit. You have a CT scan every 8 weeks.

The trial team need check your blood pressure at least once a week in the first 4 weeks of treatment. They will do this during your hospital visits. But you may also need to visit the practice nurse at your GP surgery a couple of times. Or, you may be able to check your blood pressure at home.

After you finish having treatment, you go back to see the trial doctors every 8 weeks.

Side effects

As both of the drugs in this trial are quite new, there may be some side effects we don’t know about yet. Possible side effects of cediranib include

• Feeling or being sick
• Diarrhoea
• Muscle weakness
• Sore mouth or hoarseness
• Tiredness (fatigue)
• High blood pressure
• Numbness, tingling, redness or soreness on the palms of your hands or soles of your feet (hand foot syndrome)
• Protein in the urine

Possible side effects of saracatanib include

• Feeling or being sick
• Diarrhoea
• Muscle weakness
• Flu like symptoms, such as aches and pains, fever, headache and tiredness
• Protein in the urine
• A drop in the number of white blood cells causing an increased risk of infection

If you do have side effects, the trial doctors may reduce the dose of the drugs.