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STAMPEDE: PATIENT INFORMATION SHEET-GENERAL: PART 1 (to be printed on local hospital headed paper) Version 11.0 (January 2014) 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. This sheet should be read with the “General Patient Information Sheet - Part 2” and treatment specific sheets. 2. Why is this research being done? This study is called STAMPEDE and looks at the effect of combining newer treatments with standard hormone treatment. 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. Some men may also have radiotherapy as part of their standard therapy. 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. Nowadays, this type of prostate cancer is usually referred to as hormone-refractory or, increasingly, as castrate-refractory prostate cancer and is often abbreviated to CRPC. This latter term is unpopular with patient groups due to its perceived negative overtones and hence the terminology may yet change again in the future. STAMPEDE PIS Part 1 version 11.0 Page 1 of 9 There are a number of treatments that are used for prostate cancer, either early in the disease or once it has stopped responding to standard first-line hormone treatment. We are testing these treatments in men starting long-term hormone treatment for the first time to see if they are more effective if used earlier on in the disease rather than if they are saved for use later in the disease. These treatments are listed in Table 1 below. 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. We will also be aiming to find out more about how prostate cancer develops and grows. We would like your consent to carry out a small number of additional tests to help us do this. Details of these additional studies are covered in the information sheet entitled “Additional Research” that you will have been given. Table 1: The research treatments currently being tested in this study Abiraterone (marketed as Zytiga®) This is a recently licensed hormone drug treatment, 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. Enzalutamide (marketed as Xtandi®) This is a recently licenced drug treatment with potent anti-androgens action (androgens are male hormones); it works by blocking the action of the male hormone known as androgens, slowing down the growth of the prostate cancer. Enzalutamide is already approved for men with later stages of metastatic prostate cancer who have previously received docetaxel (chemotherapy). Prostate radiotherapy for men with metastatic disease This is a standard treatment for men with localised prostate cancer that kills cancer cells in the prostate using high energy x-rays. It acts by stopping cells dividing and multiplying and destroying cancer cells in the treated area. STAMPEDE PIS Part 1 version 11.0 Page 2 of 9 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 studies 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 the study, 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 your study doctor. This is called randomisation and it ensures that the groups of people in each group of the study 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 caused by the treatment. “Randomisation” is also the best way of ensuring that the results of trials are not biased by the way treatments are selected. This is key to a fair test. You must be willing to accept whichever treatment you are allocated if you choose to join the study. We expect to include over around 7,000 men like you in this study. They will be treated at hospitals all over the UK and internationally. We expect to take between 6 and 10 years to complete recruitment to 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. Men with newly-diagnosed disease that has not spread elsewhere (non-metastatic prostate cancer) may also have radiotherapy as part of the standard-of-care. This is discussed in section 5 and your study doctor will talk to you about this. We have called the men who receive standard hormone treatment or standard hormone therapy with standard radiotherapy Treatment Group A. The other groups of men will also receive the standard therapy, plus one or two of the research treatments. We have called these Treatment Groups H and J. STAMPEDE PIS Part 1 version 11.0 Page 3 of 9 For your information, STAMPEDE previously included recruitment to five other Treatment Groups, B, C, D, E, F and G but as we already have enough men to collect the necessary information on the drugs being studied we are no longer recruiting to those arms. The results of these comparisons will not be known for some time. Details of the treatments are given in Table 2. On average, from every 3 men with metastatic prostate cancer joining the trial, 1 will be allocated the control arm (Treatment Group A), 1 to the research radiotherapy arm (Treatment Group H) and 1 to the enzalutamide + abiraterone arm (Treatment Group J). For all other men joining the trial who have prostate cancer that is not metastatic, half will be allocated the control arm and half to the enzalutamide + abiraterone arm (see Figure 1 for trial treatment allocations). These are broad average figures for the STAMPEDE trial at the moment. There are separate information sheets for each treatment group that give more details about both standard treatments and the research treatments. If you choose to join the trial you will definitely 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. Figure 1: Treatment groups in the study 1 Except pts not suitable for radiotherapy 2 All suitable patients with newly diagnosed locally advanced disease should also have radiotherapy to the prostate STAMPEDE PIS Part 1 version 11.0 Page 4 of 9 Table 2: The Research Groups in the STAMPEDE Trial Treatment Group A. Hormone Treatment If you are in Treatment Group A, you will receive the standard treatment for men with your type of prostate cancer which is hormone therapy plus, in some instances, radiotherapy. Hormone treatment 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 to hormone treatment you can choose within the trial are: (i) Chemically, by injections. 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. If your cancer has not spread, your doctor will also give you radiotherapy, about 6 to 9 months after joining the trial. Treatment would typically take between 20 and 37 sessions according to local practice. (see Section 5). Treatment Group H. Hormone treatment and prostate radiotherapy for men with metastatic disease If you are in Treatment Group H, you will receive the standard hormone treatment as described in Treatment Group A plus radiotherapy to the prostate. The radiotherapy would start within a few weeks of joining the study. It would require a visit to a CT scanner for radiotherapy planning soon after joining the trial. Treatment would commence a few weeks later and would comprise sessions of about 10 minutes. These sessions will either be once a week for 6 weeks, or 5 times a week for 4 weeks. Treatment Group J. Hormone Treatment and Enzalutamide + Abiraterone If you are in Treatment Group J, you will receive standard treatment, as described in Treatment Group A plus the combination of enzalutamide and abiraterone. Both enzalutamide and abiraterone will be given as a daily dose for up to 2 years. Enzalutamide will be taken as four 40mg capsules once a day with or without food whereas abiraterone will be taken as four 250 mg tables on an empty stomach. In addition, one 5mg tablets of steroids (prednisolone or prednisone) will need to be taken by mouth once a day. Treatments might be stopped sooner if your study doctor feels they are no longer working. STAMPEDE PIS Part 1 version 11.0 Page 5 of 9 The possible study treatment that you could receive differs slightly, depending on your situation. If you have newly-diagnosed metastatic disease, you could be allocated to any of the study treatments. If not, you will not be randomised to Treatment Group H (see Figure 1). 5. Can I also receive standard-of-care radiotherapy? Recent controlled trials like this one have shown us that there are some groups of men who we know 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. If given, standard radiotherapy should start around 6 months after starting hormone treatment. During and after the radiotherapy you would continue with hormone treatment. Treatment would typically take between 20 and 37 sessions according to local practice. Further detailed information will be given by your cancer doctor. If you have newly-diagnosed metastatic disease, radiotherapy to the prostate is not part of standard care. Therefore, we are testing whether this would be helpful in the men allocated to Treatment Group H. Figure 1 shows which treatment groups you might be allocated to. The radiotherapy would then take place as set out in Table 2 above. 6. What are the unwanted side-effects? All men joining the study will be given hormone therapy which is standard treatment. It works by reducing the level of testosterone in the body. The unwanted side-effects associated with the reduction of testosterone levels might include: impotence, decreased sex drive (loss of libido), hot flushes and, occasionally, a small amount of swelling of breast tissue. STAMPEDE PIS Part 1 version 11.0 Page 6 of 9 Long-term hormone treatment based on reduction of testosterone in the body can reduce bone density in some men, leading to an increased risk of osteoporosis (bone thinning). In most men, this does not lead to any clinical symptoms. There is no generally agreed way of dealing with this potential problem. Table 3 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. You will be given the treatment specific PIS after you are randomised, but you are very welcome to read them all now. Just ask your study doctor. STAMPEDE PIS Part 1 version 11.0 Page 7 of 9 Table 3: Possible unwanted side-effects from the research treatments Abiraterone Tiredness, raised blood pressure, fluid retention and low potassium levels in the blood which therefore need regular monitoring. Other known side effects are diarrhoea (very common), muscular weakness and damaged skeletal muscle tissue (uncommon). Enzalutamide Tiredness (fatigue), diarrhoea, hot flushes, pain in joints and muscles, headaches, dizziness, feeling weak, swollen feet and ankles due to fluid retention, increased blood pressure and an increased risk of infection due to a drop in the number of white blood cells. Some men have experienced seizures and care is recommended in men who have a history of seizures, had a prior head injury (such a stroke), have a secondary cancer in the brain or are alcoholic; however men with a history of seizures, prior head injury or secondary brain cancer will not be included in the trial. There are no known interactions between enzalutamide and abiraterone. Prostate radiotherapy for men with metastatic disease Frequent or urgent bowel movements, rectal bleeding, increased urinary frequency. More information is given in the treatment specific information sheets. 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 stop the trial treatment without giving your reasons and without affecting your future care. STAMPEDE PIS Part 1 version 11.0 Page 8 of 9 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 enzalutamide and abiraterone, the tablets will be taken daily at home but you will need some extra blood tests, particularly in the first few weeks, to be sure there aren’t any problems. If you are to receive prostate radiotherapy you will need to visit the hospital for your treatment sessions as set out in the detail of Treatment Groups A or H. 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 enzalutamide + abiraterone (Treatment Group J) 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 2 years, then at least every 6 months as part of this trial. 9. What are the possible advantages of taking part in the study? There are a number of treatments that have proved effective in the treatment of prostate cancer that has stopped responding to hormone treatment, as described above. We don’t know whether using these treatments earlier in the disease and in combination with standard hormone treatment will be better than hormone treatment alone. Therefore, your participation may not be of direct benefit to you. Your participation will, however, help to answer these questions and help us to improve treatment for men like you in the future. 10. What are the possible disadvantages? In this trial you may be asked to receive additional treatment(s) as well as the hormone treatment. We do not expect there to be any disadvantage to you in terms of how your cancer responds but the additional treatments may have some additional side-effects (Table 3). There will also be some extra hospital visits and blood tests, as described above. If you want to know more, please read the next section. End of PIS Part 1 Please read PIS Part 2 for detailed information Please read treatment specific PIS as relevant STAMPEDE PIS Part 1 version 11.0 Page 9 of 9