STAMPEDE: PATIENT INFORMATION SHEET-GENERAL
(to be printed on local hospital headed paper)
Version 8.0 (02 Sep 2011)
A LARGE PRINT VERSION IS AVAILABLE ON REQUEST
STAMPEDE: Systemic Therapy in Advancing or Metastatic Prostate Cancer - Evaluation of Drug Efficacy
1. General Information
Your doctor has explained to you that you have prostate cancer and has invited you to participate in this clinical trial. Before you decide, it is important for you to understand why the research is being done and what it will involve. Participation is entirely voluntary. If you decide not to take part, your decision will be accepted without question, and your subsequent treatment will not be affected in any way.
2. Why is this research being done?
Prostate cancer often depends upon the male hormone (testosterone) to grow. One of the main ways of treating prostate cancer involves hormonal treatment to reduce the level of testosterone in the body.. This is achieved by using a range of drugs which reduce the signals to the testicles so they do not make the hormone or by surgically removing the part of the testicles that produces testosterone.
Hormone treatment is usually successful at first: further growth of the cancer is prevented and it will usually cause the cancer to shrink. However, after a period of time the cancer can begin to grow again. This type of prostate cancer is called castrate refractory prostate cancer often abbreviated to CRPC. A previous term for this condition was hormone refractory prostate cancer abbreviated to HRPC.
There are a number of drugs that are used in the treatment of prostate cancer once it has stopped responding to standard first-line hormone treatment. We are testing these drugs in men starting long-term hormone treatment for the first time to see if they are more effective if used earlier on rather than if they are saved for use later in the disease. These drugs are listed in Table 1 below.
This trial is called STAMPEDE and looks at the effect of combining one or two of these newer drug treatments described above with standard hormone treatment. In addition to studying the effect of the treatment on the growth of your cancer, we will also be asking how it has affected your quality of life and we will be aiming to find out more about how prostate cancer develops and grows. We would like your permission to carry out a small number of additional tests to help us do this. The knowledge derived from these tests will help us to better understand the disease and help treat patients like you in the future. Details of these additional studies are covered in the information sheet entitled “Additional Research” that you will have been given.
Table 1: The newer drugs in this studyZoledronic acid (Zometa®)
Prostate cancer cells can spread to bones and weaken them. It is currently used in men when the cancer has spread to the bones after the cancer has stopped responding to standard hormone treatment. Zoledronic acid reduces bone destruction and hardens the normal bone; this may make them more resistant to attack by cancer cells.
Docetaxel (Taxotere®)
This is a chemotherapy drug that stops cells dividing and multiplying. It is currently used to treat prostate, lung, breast and ovarian cancers. Docetaxel, in combination with a steroid (either prednisolone or prednisone), is approved by regulatory authorities for the treatment of castrate refractory prostate cancer (cancer that is no longer responsive to standard firstline hormone treatment).
Abiraterone (Zytiga®)
This is a recently licensed hormone treatment drug, taken as a daily tablet combined with a steroid (either prednisolone or prednisone). It acts on one of the ways that prostate cancer cells use to bypass the standard hormone therapies. It is approved for use in men whose cancer has stopped responding to both hormone treatment and who have also previously received docetaxel chemotherapy.
3. How is the research done?
The best way of determining whether one treatment is more effective than another is by carrying out a clinical trial called a “randomised controlled trial”. These aim to make a fair comparison between new treatments and the existing treatment to see which one works best. A controlled trial compares two or more groups of people: a research group who receive the research treatment and a control group who receive the standard treatment. This allows researchers to see whether the treatment they are testing is any more or less effective than the existing treatment. If you join a trial, the decision about which group you will join is random – based on chance. A computer programme will allocate which treatment group you would join, not you nor the doctor. This is called randomisation and it ensures that the groups of people in a trial are as similar as possible, except for the treatment they receive. This is important because it means that researchers can be sure that any differences in outcomes between the groups are therefore only due to the treatment. Randomisation is also the best way of ensuring that the results of trials are not biased by the way treatments are selected and is key to a fair test. You should, therefore, be willing to accept whichever treatment you are allocated.
We are aiming to include approximately 4,000 men like you in this study (Figure 1). They will be treated at hospitals all over the UK and elsewhere and it is expected that it will take between 6 and 10 years to complete the study.
4. Which treatment might I receive if I take part?
All men taking part in the trial will receive hormone treatment which is standard treatment for your type of prostate cancer. We have called the men who receive hormone treatment on its own Treatment Group A.
The other men will receive hormone treatment plus one or two of the newer drugs, and we have called these Treatment Groups B, C, E and G.
For information, the study previously included two further arms, D and F, but no new men are allocated to these groups now as we do not need further information on the drug being studied in these arms.
Details of the treatments are given in Table 1. At this stage in the study, two out of seven men in the trial can expect to join Group A (hormone therapy only). In addition, two out of seven men can expect to receive hormone treatment + abiraterone (arm G) The remaining three out of seven men will be allocated equally between arms B, C and E.
There are separate information sheets for each treatment group that give more details about both hormone treatment and the newer drugs. If you choose to join the trial you will be given the sheet for the treatment group you are allocated at that time, but you are very welcome to read all of these at any time, including now.
Table 1: The Different Treatment Groups in the STAMPEDE Trial.A. Hormone Treatment Only
If you are in Treatment Group A, you will receive hormone treatment only. This is the standard treatment for patients with your type of prostate cancer. Hormone therapy reduces the testosterone level in the body. It is sometimes called androgen suppression or androgen deprivation therapy. Your study doctor will discuss the different types of hormone treatment and together you can decide on the most suitable way for you. The two approaches within the trial are:
(i). Chemically, by an injection. These are usually administered once a month or once every three months, though longer acting preparations are becoming available
(ii). Surgically, by an operation. The functioning parts of both testicles are removed. This called an orchidectomy and is sometimes called bilateral orchidectomy.
B. Hormone Treatment and Zoledronic Acid
If you are in Treatment Group B, you will receive hormone treatment as described in Treatment Group A plus zoledronic acid. Zoledronic acid will be given as an injection into a vein once every three weeks, for 6 injections, and then once every four weeks for up to two years.
C. Hormone Treatment and Docetaxel
If you are in Treatment Group C, you will receive hormone treatment as described in Treatment Group A plus docetaxel. Docetaxel will be given as an injection into a vein once every three weeks, for a total of 6 injections. You will also be given steroid tablets (prednisolone in the UK) to take while you are on docetaxel.
E. Hormone Treatment and Zoledronic Acid and Docetaxel
If you are in Treatment Group E, you will receive hormone treatment as described in Treatment Group A plus both zoledronic acid and docetaxel. Zoledronic acid and docetaxel will be given as separate injections into a vein once every three weeks for the first 6 injections. Then only zoledronic acid will continue to be given, once every four weeks, for up to two years. You will also be given steroid tablets to take while you are on docetaxel.
G. Hormone Treatment and Abiraterone
If you are in Treatment Group G, you will receive hormone treatment as described in Treatment Group A plus Abiraterone. Abiraterone will be given as a daily dose of 1g (four tablets) for up to 2 years. The tablets need to be taken on an empty stomach. In addition, you will need to take either prednisolone or prednisone (which are steroid tablets) daily while you are on abiraterone.
5. Can I also receive radiotherapy?
If your doctor thinks it is right for you, you can also receive radiotherapy (RT) at any time in the trial. Recent controlled trials like this one have shown us that there are some groups of men who should receive radiotherapy as part of their standard care:
(i) If you have disease that is confined to the prostate, we recommend that radiotherapy be given unless there are specific reasons not to give it (for example, certain bowel problems). The trial includes recommended guidelines for giving radiotherapy but these can be modified to fit local practice in your hospital.
(ii) If your disease is confined to the prostate gland and lymph glands nearby in the pelvis, we also recommend that radiotherapy be included as part of your standard care, if your doctor thinks it is feasible in your case.
It is now standard practice to plan for radiotherapy to start after a period of hormone treatment, as other studies have shown this improves outcomes for men. If given, radiotherapy treatment on any of the study arms should start around 6 months after starting hormone treatment and, for men in groups C and E, after chemotherapy has finished, since receiving radiotherapy and chemotherapy at the same time can cause additional unwanted side-effects. During and after the radiotherapy you would continue with hormone treatment. The radiotherapy would require a visit to a CT scanner for radiotherapy planning. Treatment would commence a few weeks later and would comprise daily sessions of about 15 minutes. Treatment would typically take between 20 and 37 sessions according to local practice. Further detailed information will be given by your cancer doctor.
6. What are the unwanted side-effects?
The unwanted side-effects associated with the reduction of testosterone levels in the body might include; impotence, decreased sex drive (loss of libido), hot flushes and occasionally, a small amount of swelling of breast tissue.
Long-term hormone treatment based on reduction of testosterone in the body can affect bone density in some men, leading to an increased risk of osteoporosis (bone thinning). In most men, this should not lead to any clinical symptoms. There is no generally agreed way of dealing with this potential problem.
Table 2 outlines the most common unwanted side-effects that can occur with the newer treatments. More details on the potential unwanted side-effects from the research treatments are given in the arm-specific Patient Information Sheets.
Table 2: Possible unwanted side-effects from the newer treatmentsZoledronic acid
Flu-like symptoms, e.g. raised temperature and body aches. Uncommonly, zoledronic acid can cause breakdown (osteonecrosis) of the jaw.This is associated with long-term use of zoledronic acid (usually over 36 months), particularly in patients who have dental disease.Zoledronic acid should be discontinued if you need a tooth extraction.
Docetaxel
Hair loss, allergic reactions, fluid retention, sickness, anaemia. Also it may lower the level of other blood cells making you more susceptible to bruising, bleeding and infections.
Abiraterone
Tiredness, raised blood pressure, fluid retention and low potassium levels in the blood which therefore need regular monitoring).
7. Do I have to take part in the study?
Your participation in the STAMPEDE study is entirely voluntary. If you decide not to take part, your decision will be accepted without question and your subsequent treatment will not be affected in any way. The standard treatment for your type of prostate cancer is hormone treatment. All men taking part in the trial will receive a form of hormone treatment as well as radiotherapy, if appropriate. If you agree to take part you are free to withdraw from the trial treatment without giving your reasons and without affecting your future care.
8. What will happen to me if I take part in the study?
Whether you receive your treatment in hospital or at home will depend on the treatment group you are in. If you are to receive docetaxel, it will be given to you in a specialised ward or unit: <insert where this would be>. If you are to receive zoledronic acid you will also need to make extra visits to your hospital for treatment: <insert where this would be>. If you are to receive abiraterone, the tablets will be taken daily at home but you will need to some extra blood tests, particularly in the first few weeks, to be sure there aren’t any problems. If you agree to take part in the trial, there will be some additional blood tests to measure the progress of your cancer (approximately 6 in the first 2 years). If you are to receive zoledronic acid, docetaxel or abiraterone (Treatment Groups B, C, E or G) there will be some more blood tests to monitor the safety of your treatment. Your study doctor will see you at least every 3 months for 3 years, then at least every 6 months as part of this trial.