A trial looking at Zibotentan (ZD4054) for prostate cancer that has come back after hormone treatment (D4320C00015)

Please note this trial is no longer recruiting patients.

This trial is looking at a new drug called zibotentan (ZD4054) for prostate cancer that has come back after hormone treatment. It is for men who have a rising PSA level but no signs that the cancer has spread to another area of the body (metastasised).

Most men with early stage prostate cancer are treated successfully. But for some men the cancer comes back. Doctors often pick this up because the PSA level starts to rise.

If this happens, many men will have hormone treatment. This can work very well but unfortunately the cancer often starts to grow again in time, causing the PSA level to rise again. This is called hormone refractory prostate cancer. It is not clear what the best treatment is in this situation.

Zibotentan is a type of biological therapy. It works by blocking growth receptors on cancer cells called endothelin receptors. It can be called an endothelin blocker or endothelin receptor antagonist. We know from earlier trials that endothelin blockers may be able to slow down the growth of prostate cancer.

In this trial, doctors want to see if zibotentan helps men with hormone refractory prostate cancer to live longer. As all treatments have side effects, it is important that people do not have treatments that don’t work. The doctors are comparing zibotentan to a dummy drug (placebo).

The aims of this trial are to

Find out if zibotentan helps to slow down the growth of hormone refractory prostate cancer that hasn’t spread to other areas of the body
Learn more about the side effects

Recruitment

Start 15/01/2008

End 31/12/2010

Phase

Phase 3

Who can enter

You can enter this trial if

You had an operation to remove your testicles (an orchidectomy) or started hormone treatment at least 8 weeks ago for prostate cancer that had come back, and your PSA level has started to rise again
There are no signs of cancer on a CT scan, MRI scan or bone scans
The level of testosterone in your body is very low (less than 70ng/dl or nanograms per decilitre)
You have satisfactory blood test results
You are well enough for treatment (performance status 0 or 1)
You are at least 18 years old

You cannot enter this trial if you

Have had surgery, radiotherapy or cryotherapy for prostate cancer in the last 3 months
Have had chemotherapy or a type of biological therapy that blocks cancer growth, such as VEGF or EGFR, for prostate cancer that has come back (you can still take part if you had a chemotherapy drug called estramustine)
Have had bisphosphonates through a drip into a vein in the last 6 weeks (if you are taking bisphosphonates by mouth to prevent or treat osteoporosis you may still be able to take part)
Are taking strong painkillers called opioids for pain caused by your prostate cancer
Have taken drugs which are broken down by an enzyme called CYP450 (such as phenytoin, rifampicin, carbamazepine, phenobarbitone and St. John’s Wort) in the last 2 weeks
Have had treatment with drugs similar to vitamin A (called retinoids) in the last 2 weeks
Have had experimental treatment as part of a clinical trial in the last 4 weeks
Have had treatment with drugs similar to ZD4054 (endothelin blockers) before or have a family history of sensitivity to these types of drugs
Have a history of fits (seizures) or epilepsy
Have heart failure or have had a heart attack in the last 6 months
Have any other serious medical condition that means you cannot have the treatment in this trial
Have had any other cancer in the last 5 years, except non melanoma skin cancer which has been successfully treated

Trial design

This is a phase 3 trial and will recruit about 1,500 men worldwide. The men taking part are put into 2 different groups by computer. Neither you nor your doctor will be able to decide which group you are in, or will be told which group you are in. This is called a double blind trial.

Group 1 will have zibotentan (ZD4054). Group 2 will have a dummy drug (placebo). You take one zibotentan tablet or placebo tablet every morning.

You continue with the treatment for as long as the doctors feel it is working and you don’t have any serious side effects. They may decide to add in other treatments if your PSA continues to rise or your cancer is causing symptoms.

Your doctors may ask to take some extra blood samples to help with further research. Doctors know that people’s genes may affect how well some drugs work, but they need to learn more about this. They would also like to use it to learn more about biological markers for prostate cancer. This may help doctors in the future predict whether someone will benefit from a treatment.

They may also ask to keep tissue samples taken when you were first diagnosed with prostate cancer or during treatment. This is so that researchers can learn more about prostate cancer and how it responds to treatment. If you do not wish to give these samples, you do not have to. You can still take part in the trial.

You will fill out 2 short questionnaires

Before you start treatment
Every 4 months during treatment
When treatment finishes
Every 4 or 6 months after that

The questionnaires will ask about how you have been feeling and any changes to your daily activities. These are called quality of life questionnaires.

Hospital visits

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

Physical examination
Heart trace (ECG)
Blood tests
Urine sample
Bone scan
CT scan or MRI scan of the pelvis and abdomen

You will see the doctors every 4 weeks for the first 4 months so they can see how you are and repeat some of these tests. You then go to the hospital to see your doctor every 4 months. You have scans every 8 months.

Even if your cancer starts to grow again, your doctor may decide to continue with the drug if they feel it is helping. If this happens you will see the doctors every 6 months.

You will have some of the tests again when you finish treatment and about a month later.

You will continue to go to the hospital every 4 to 6 months for follow up appointments. If you are unable to go to the hospital, your doctor or nurse may contact you by phone.

Side effects

All treatments have side effects. As zibotentan (ZD4054) is a new drug there may be some side effects that the doctors don’t know about yet. In trials so far, the most common side effects are