A trial of TPF chemotherapy before surgery and radiotherapy for locally advanced head and neck cancer (TITAN)

This trial is looking at chemotherapy before surgery and radiotherapy for people who have squamous cell cancer of the head and neck. This includes cancer that started in the mouth, nose, sinuses, throat or voicebox (larynx).

If you have head and neck cancer that has grown into surrounding body tissues (locally advanced cancer), you usually have surgery followed by either radiotherapy or a combination of radiotherapy and chemotherapy (chemoradiation). This is standard treatment.

But sometimes the cancer will come back and doctors are looking for ways to improve treatment. In this trial, they are looking at chemotherapy before surgery. This is called induction chemotherapy. It is a combination of 3 drugs called docetaxel, cisplatin and fluorouracil. This combination of drugs is also known as TPF.

We know from research that TPF can shrink head and neck cancers. But we don’t know if having this type of chemotherapy before surgery makes a difference to the long term outcome.

The aim of the trial is to see if having induction chemotherapy before standard treatment helps people with locally advanced squamous cell cancer of the head and neck.

Recruitment

Start 01/11/2011

End 01/08/2012

Phase

Phase 3

Who can enter

You may be able to enter this trial if you

Have squamous cell cancer in your head or neck
Have a cancer that has grown into surrounding tissue (locally advanced) but has not spread anywhere else in your body
Are going to have surgery to remove your cancer
Are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
Have satisfactory blood test results
Are willing to use 2 forms of contraception (including condoms) if there is any chance you or partner could become pregnant
Are at least 18 years old

You cannot enter this trial if you

Have nasopharyngeal cancer
Have cancer that started in the oropharynx and is HPV positive (your doctor can advise you about this)
Have cancer that has grown into your jaw bone
Have cancer that cannot be removed with surgery
Have another medical condition or need to take medication that would mean you can’t have the induction chemotherapy
Have liver or kidney problems (the trial doctors will check for this)
Are pregnant or breastfeeding

Trial design

To begin with, this is a pilot study that will recruit about 50 people. But the researchers hope it will become a large phase 3 trial that will recruit about 420 people all together.

It is a randomised trial. The people taking part are put into treatment groups by computer. Neither you nor your doctor will be able to decide which group you are in.

Group A have surgery followed by radiotherapy or chemoradiation (standard treatment)
Group B have induction chemotherapy before having standard treatment

People in group B have chemotherapy in 3 week cycles of treatment. You have docetaxel and cisplatin through a drip into a vein on the first day of each cycle. You have fluorouracil through a drip into a vein over the first 4 days of each cycle. You have 3 cycles of treatment lasting 9 weeks all together, then you have surgery.

The trial team will ask you to fill out some questionnaires before you start treatment and at your follow up visits after you finish treatment. The questionnaires will ask about any side effects you have had and about how you have been feeling. This is called a quality of life study.

The researchers will ask your permission to take an extra blood sample and to keep some tissue samples. They will use these samples to look at your DNA and learn more about head and neck cancer and how different people respond to treatment. They can use some of the tissue removed when you had a biopsy to diagnose your cancer. They may also keep some tissue they remove during surgery. If you don’t want to give these samples for research, you don’t have to. You can still take part in the trial.

Hospital visits

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

Physical examination
Blood tests
PET-CT scan
Heart trace (ECG)

If you are in group B, you have extra hospital visits to have chemotherapy. You may be able to have treatment as an outpatient, but you may need to stay in hospital for 4 days each time. This will depend on where you are having your treatment.

You have a PET-CT scan at the end of the 1st cycle of treatment and you may need to have another one after the 3rd cycle to see how your cancer has responded to the chemotherapy.

Everybody taking part will spend time in hospital to have surgery and you will go to hospital a number of times to have radiotherapy or chemoradiation.

You will see the trial doctors for follow up appointments every 3 months for the first 2 years, then once a year for the next 3 years.

Side effects

The side effects of TPF chemotherapy include

A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
Hair loss
Changes to your nails
Skin rash
Feeling or being sick
Diarrhoea
Damage to your liver, kidneys or heart
A tingling sensation in your hands or feet
Hearing loss
Tiredness (fatigue)
Sore mouth