A trial looking at docetaxel and RAD001 for head and neck cancer that has spread or has come back after treatment (DORA)

Who can enter

You can enter this trial if you

• Have squamous cell cancer of the head or neck that has spread from where it first started, or has come back after treatment
• Are well enough to take part in the study and have a performance status of 0 or 1
• Have satisfactory blood test results
• Are willing to use reliable contraception during the trial if there is any chance you or your partner could become pregnant
• Are able to take tablets
• Are at least 18 years old

You cannot enter this trial if

• You have cancer that has spread to your brain or spinal cord (the central nervous system)
• Your doctors believe they can cure your cancer or think it would be better for you to have radiotherapy
• You have had chemotherapy for any other type of cancer, or have already had more than one type of chemotherapy for head and neck cancer
• You have already had one of a group of drugs called taxanes
• You have had radiotherapy in the last 6 months
• You have had any drug that targets growth factors apart from cetuximab (your doctor can advise you about this)
• You have had any other experimental drug as part of a clinical trial in the last 4 weeks
• You take drugs that block an enzyme called CYP3A4 (you can check this with your doctor)
• You have an infection that cannot be controlled with medication
• You have had any other type of cancer that may affect how you cope with treatment in this trial
• You are pregnant or breast feeding
• You are known to be hepatitis B or hepatitis C positive

Trial design

The trial is in 2 parts. The first part (phase 1) is trying to find the highest dose of RAD001 that you can have safely at the same time as docetaxel. The first few patients will have a low dose of RAD001. If they don’t have any serious side effects, the next few patients will have a higher dose. And so on, until they find the best dose to give. This is called a ‘dose escalation study’.

You have docetaxel through a drip into a vein once every 3 weeks. This takes about an hour each time. You take RAD001 as tablets once a week. Each 3 week period is called a cycle of treatment. You can have up to 6 cycles of treatment, taking between 4 and 5 months all together. If the treatment is helping, you may carry on taking RAD001 after you finish having docetaxel.

The second part of the trial (phase 2) will compare the combination of RAD001 and docetaxel, with docetaxel alone. It will recruit about 100 people, who will be put into one of two groups by a computer. This is called randomisation. Neither you nor your doctor will be able to decide which group you are in.

If you are in group A, you have docetaxel every 3 weeks.

If you are in group B, you have docetaxel every 3 weeks, and RAD001 tablets once a week. You will have the highest safe dose of RAD001 that the doctors found in the dose escalation study. If the treatment is helping, you may carry on taking RAD001 after you finish having docetaxel.

If you agree to take part in this trial, the researchers will ask your permission to get a sample of the tissue taken when you had surgery or a biopsy. And they will ask to take an extra blood sample before you start treatment. These samples will be stored safely and may be used in the future for research purposes. If you don’t want to give samples for research, you don’t have to. You can still take part in the trial.

The researchers may also ask to take another biopsy 3 weeks after you start treatment. This is to learn more about what effect the treatment has on head and neck cancer.

Hospital visits

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

• Physical examination
• Blood tests
• MRI scan or CT scan

You go to hospital once every 3 weeks to see the doctors, have blood tests and have the docetaxel. If you are taking part in phase 1, you have a number of extra blood tests during the first 2 cycles of treatment. This will mean going to hospital a few more times.

During your treatment, you have regular chest X-rays and a scan after every 2 cycles of treatment. After you finish treatment, you will see the trial doctors and have a scan every 3 months.

Side effects

Docetaxel can cause an allergic reaction. To try to prevent this, you have steroid tablets called dexamethasone for 3 days each time you have docetaxel. Other side effects of docetaxel include

• Tiredness (fatigue)
• Hair loss
• A drop in the number of blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
• Sore mouth
• Diarrhoea
• Sickness

The possible side effects of RAD001 include

• Sore mouth
• A drop in the number of blood cells causing an increased risk of infection
• Skin rash
• Tiredness and headaches
• Sickness
• Diarrhoea

Rarely, RAD001 can cause high cholesterol levels in the blood, high blood pressure, low testosterone levels, blood clots, bruising or bleeding problems and lung damage.

The trial team will give you a mouthwash to use everyday during to treatment to try to reduce the risk of your mouth getting sore.

You must not chew or crush the RAD001 tablets, and you must not drink grapefruit juice or other citrus fruit juice when you take them. You should not take St John’s wort during the trial as it may interfere with the way RAD001 works.