A trial looking at hormone therapy with zoledronic acid, docetaxel or celecoxib for prostate cancer (STAMPEDE; MRC PR08)

This trial is comparing hormone therapy alone and hormone therapy in combination with either zoledronic acid, docetaxel or celecoxib for prostate cancer.

Hormone therapy is often used to treat prostate cancer that has spread outside the prostate gland. It can work very well, but the cancer often starts to grow again at some stage. Doctors think that using other treatments at the same time as hormone therapy may work better. But they are not sure yet how well they will work.

In this trial, patients will have hormone therapy as they usually would. But some will have other treatments as well. The treatments are a bisphosphonate called zoledronic acid (zoledronate or Zometa), a chemotherapy drug called docetaxel (Taxotere), and a COX 2 inhibitor called celecoxib. The different treatment groups are explained in the ‘trial design’ section below.

The aim of this trial is to see which treatment is best for prostate cancer that has spread outside of the prostate gland.

Recruitment

Start 19/09/2005

End 01/12/2013

Phase

Phase 3

Who can enter

You can enter this trial if you have either

Recently been diagnosed with prostate cancer that has spread outside the prostate gland and also have a PSA level of 40 or above, or a Gleason score of 8 or above, or
Prostate cancer that has started to grow again following surgery or radiotherapy

As well as that, you must

Be due to have hormone treatment for your prostate cancer
Be well enough for treatment (performance status 0, 1 or 2
Have satisfactory blood test results

You cannot enter this trial if you

Have prostate cancer that has spread to the brain
Have any other cancer that the doctors think may affect the treatment or the trial results
Have numbness or tingling in your hands or feet (peripheral neuropathy)
Have had surgery for prostate cancer in the past 4 weeks
Have taken a COX 2 inhibitor drug for 6 months or more
Have poor kidney function
Have a serious heart condition, or have had a heart attack or stroke in the past

Trial design

This is a randomised trial. The research team have completed the pilot study, and are now recruiting a total of 3,300 men to the full trial. The trial has 6 groups. The men taking part will be put into treatment groups by a computer. Neither you nor your doctors will be able to decide which group you are in.

All men taking part will have hormonal treatment. This could be hormone injections, tablets or implants. Or an operation to remove both testicles (an orchidectomy). The hormone testosterone is made the testicles, so if they are removed, the level of testosterone falls dramatically. If you are in group 1, you will not have any other treatment.

Group 1 will have hormone therapy or an orchidectomy
Group 2 will have hormone therapy or an orchidectomy, plus zoledronic acid (zoledronate or Zometa)
Group 3 will have hormone therapy or an orchidectomy, plus docetaxel (Taxotere)
Group 4 will have hormone therapy or an orchidectomy, plus celecoxib
Group 5 will have hormone therapy or an orchidectomy, plus zoledronic acid and docetaxel
Group 6 will have hormone therapy or an orchidectomy, plus zoledronic acid and celecoxib

If you are in group 2, 5 or 6, you will have zoledronic acid as an injection into a vein once every 3 weeks for 18 weeks. Then once every 4 weeks for up to 2 years.

If you are in group 3 or 5 you will have docetaxel into a vein once every 3 weeks for 18 weeks. You will also take steroid tablets called prednisolone every day during this time. If you are in group 5, you will have zoledronic acid and docetaxel as separate injections on the same day, every 3 weeks for the first 18 weeks. You then have zoledronic acid every 4 weeks for up to 2 years.

If you are in group 4 or 6 you will take celecoxib tablets twice a day for up to year.

You will fill out a questionnaire when you start treatment, then again at 6 weeks, 3 months, 4 months, 6 months and 1 year. And then once a year after that. The questionnaire will ask you how you are feeling and about any side effects you have had. This is called a quality of life questionnaire.

Hospital visits

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

CT scan or MRI scan
Bone scan
Chest X-ray
Heart trace (ECG)
Blood tests (including a PSA test)
Physical examination

How often you go to the hospital for treatment will depend on which group you are in. There is more detail about this in the ‘trial design’ section above.

As part of this trial you will see the doctors every 3 months for 3 and a half years, and then every 6 months after that.

Side effects

The most common side effects of hormone therapy or orchidectomy are

Impotence
Decreased sex drive
Hot flushes
Breast swelling and tenderness

The most common side effects of zoledronic acid are

Flu like symptoms
Tiredness

The most common side effects of docetaxel are

Hair loss
Rash
A drop in blood cells causing an increased risk of infection, bleeding or bruising problems, tiredness or breathlessness
Swelling of hands and feet (fluid retention)
Feeling or being sick
Sore mouth
Diarrhoea

The most common side effects of celecoxib are