A trial looking at zoledronate or ibandronate for breast cancer that has spread to the bones (ZICE trial)

Please note this trial is no longer recruiting patients.

This trial is comparing bisphosphonate through a drip with bisphosphonate tablets for bone weakness and bone pain caused by breast cancer that has spread.

When cancer spreads to the bone, it can make the bone weaker and more prone to damage and fractures. It can also be painful. Drugs called bisphosphonates can help to slow down damage to the bones and reduce the pain caused by cancer that has spread. Zoledronate (Zometa or zoledronic acid) and ibandronate (Bondronat) are both bisphosphonates.

Doctors commonly prescribe zoledronate, which you have though a drip into a vein once every 3 to 4 weeks. But there is a newer bisphosphonate called ibandronate, which you can take as a tablet.

The aim of this trial is to see if ibandronate tablets are as good as intravenous zoledronate for breast cancer that has spread to the bone. The research team will see if there are any differences between bone strength, pain, side effects and quality of life.

Recruitment

Start 04/01/2006

End 18/10/2010

Phase

Phase 3

Who can enter

You can enter this trial if you

Are a man or woman with breast cancer that has spread to your bones (bone metastases)
And your doctor have agreed to treat your bone metastases with a bisphosphonate in the last 3 months, but you have not started yet
Are well enough to take part in this trial (performance status 0, 1 or 2)
Have satisfactory blood and urine test results
Are at least 18 years old

You cannot enter this trial if you

Have breast cancer that has spread to your brain
Have dental problems such as a tooth infection, jaw injury or have had osteonecrosis of your jaw in the past
Have had dental or jaw surgery in the last 8 weeks, or are due to have surgery soon
Have had bisphosphonate treatment in the last 6 months (you will still be able to take part if you are having chemotherapy or hormone therapy at the moment)
Are unable to take tablets
Have an active stomach ulcer
Are pregnant or breastfeeding

Trial design

This is a randomised trial. It will recruit 1,400 people into 2 groups. 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.

If you are in group 1 you will have zoledronate through a drip into a vein once every 3 to 4 weeks, for nearly 2 years (96 weeks). If you have chemotherapy at any point during this time, you will have zoledronate every 3 weeks. This is so you don’t have to make extra trips to the hospital to have zoledronate in between chemotherapy treatments. But apart from that, you are likely to have it every 4 weeks.

If you are in group 2 you will take ibandronate tablets once a day for nearly 2 years (96 weeks). You will need to take the tablets in the morning on an empty stomach, about half an hour before food.

You will fill out a questionnaire before you start treatment, and again every 3 months (12 weeks). It will ask you how you have been feeling and about any side effects you have had. This is called a quality of life questionnaire.

You will also fill in a questionnaire about your pain. It will ask you how bad your pain has been for the last 7 days, and roughly how many painkillers you have needed to take. You will do this before you start treatment, then every 3 to 4 weeks for 3 months, and every 3 months after that.

Hospital visits

You will see the doctors and have some tests before you take part in the trial. The tests include

Blood tests
Urine test
X-rays of your spine
Physical examination

Both groups will see a research nurse and have a blood test every 3 to 4 weeks up until week 12 (3 months). Both groups will then see the trial doctors and have more blood tests every 3 months throughout the rest of the trial.

If you are in group 1 you will also have zoledronate every 3 to 4 weeks. After 3 months you will continue to have zoledronate every 3 to 4 weeks, but you will not have to see the research nurse.

If you are in group 2, at each visit the doctor will also give you another 12 week supply of ibandronate tablets to take at home.

At the end of treatment, everyone will see the doctors and have spinal X-rays and more blood tests. After that you will see the doctors once a year for 3 years.

Side effects

As with all treatments, both zoledronate and ibandronate have some side effects.

Both drugs can cause

A drop in the level of calcium in your blood (you may need to take calcium and vitamin D supplements if this happens)
Feeling or being sick
Indigestion or tummy pain
Tiredness

Zoledronate can also cause

Flu like symptoms
Headaches

Ibandronate can also cause

Pain on swallowing
Inflammation of your gullet (oesophagus) or heartburn

There is a possible link between bisphosphonates and a condition called osteonecrosis of the jaw. ‘Osteo’ means bone and ‘necrosis’ means cell or tissue death. So in simple terms, osteonecrosis is death of bone tissue in the jaw.

But no one is certain of the link with bisphosphonates yet. There are other conditions and treatments that increase the risk of osteonecrosis. These include radiotherapy to the head and neck area, recent dental surgery, and problems with gum disease or infection. There is more information about osteonecrosis and bisphosphonates on CancerHelp UK.