Download CROP PIS and CF_Version3.1_02Feb2012

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INFORMATION SHEET FOR PATIENTS IN A CLINICAL RESEARCH PROJECT
Title of Project
A randomised controlled trial of deferred androgen deprivation therapy ± upfront
cryotherapy in men with localised radiation recurrent prostate cancer (RRPC) to
evaluate efficacy and tolerability
(Acronym – CROP: CRyOtherapy in Prostate cancer)
General Information
You are being invited to take part in a research study. Before you decide if you wish to take
part, it is important for you to understand why the research is being done and what it will
involve. Please take time to read the following information carefully and discuss it with family or
friends if you wish. Ask us if there is anything that is not clear or if you would like more
information.
Why is this research being done?
There is significant uncertainty regarding the most effective treatment for patients with
recurrent prostate cancer following previous radiotherapy. Among the available treatment
options, none have been formally assessed in a clinical trial. A period of monitoring followed by
hormone treatment, and prostate cryotherapy are two of the most commonly used treatments.
Both have been shown to be effective but we do not know which one is best in your situation.
In 2008, the National Institute for Health and Clinical Excellence (NICE) issued guidelines for
prostate cancer treatment. Although prostate cryotherapy is currently used to treat patients with
radiation recurrent prostate cancer in many centres worldwide, the guidelines concluded that
cryotherapy should only be used as part of a clinical trial. NICE say that there is not yet enough
evidence available on the long term benefits of this treatment or its effects on your quality of
life. This is why we are doing this study, to find this out.
This study aims to answer this question by comparing the effectiveness of prostate cryotherapy
followed by hormone treatment when necessary, compared to hormone treatment when
necessary alone. We will also formally compare the quality of life of patients following either
treatment options.
Purpose of the Study?
Prostate cryotherapy aims to eradicate prostate cancer by freezing prostate cells and it is not yet
standard of treatment for patients. The purpose of the study is to test how effective treatment
with cryotherapy is when compared to (delayed) hormone treatment which has been used over
several decades. At the present time, the majority of patients are treated with hormone
treatment which can be considered as the ‘standard’ of care. In addition, the timing when
hormone treatment should be started is also not clear in the literature and something else we
hope to find out in the study.
.
CROP: CRyOtherapy in Prostate cancer
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How is the research done?
The best way of determining which of the two treatment options is more effective is by carrying
out a randomised controlled study. To do this we put people randomly into groups and give
each group a different treatment (referred to as a treatment ‘arm’). The results are compared to
see if one treatment is better than the other. To try to make sure the groups are the same to
start with, each patient is put into a group by chance (randomly). The results are then
compared. You have a 50:50 chance of being entered into either group of the study. This
means that a computer will allocate which treatment you receive randomly and you will have a
chance of receiving one of the two options. Neither you nor your doctor can choose the
treatment you will receive.
We are aiming to include over 500 men like you in this study. They will be treated at hospitals
all over the UK at centres taking part in this study, and it is expected that it will take over 8
years to complete this study.
Why can’t the doctor or nurse choose the best treatment for me?
We would like this to be the case, but at the moment we do not know which treatment is best
for which patient. We need to have studies that allow us to compare the advantages and
disadvantages of the treatments and find out what men feel about these. At the moment, we do
not have this evidence and this is why we are doing the study.
Why am I being invited to take part?
Your doctor has explained to you that your prostate cancer has returned despite previous
radiotherapy, and has invited you to participate in this study as it is looking at two of the
treatment options.
What are the treatment options within the CROP study?
We are comparing the two most commonly used treatment considered in your situation. All
patients taking part in this study will receive hormone therapy and half of the patients will also
receive prostate cryotherapy:
Arm A: A period of monitoring followed by hormone therapy alone
Arm B: Upfront Prostate Cryotherapy + a period of monitoring followed
by hormone therapy
Both of these treatments are considered reasonable options for relapsed prostate cancer
following previous radiotherapy. In patients receiving hormone treatment, most patients would
undergo a period of careful monitoring of their prostate test (PSA) and the hormone treatment
will be started once the prostate (PSA) test reaches a certain level, which is 20 ng/ml in this
study, a typical level used in most practice.
Further details on hormone treatment and prostate cryotherapy can be found in the treatment
arm specific information sheets.
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What is ‘Hormone Treatment’?
Prostate cancers often depend upon the male hormone testosterone to grow. Reducing the
amount of testosterone in the body or blocking its effect usually prevents further growth of the
cancer and may cause it to shrink. This is called hormone treatment and can be achieved either
by the use of anti-hormone injections, anti-hormone tablets or an operation to remove part or
all of both testicles, which produce the male hormone. Your doctor will discuss these different
options with you and together you can decide which is the best form of hormone treatment for
you. All forms of hormone treatment can cause the following side-effects: impotence, loss of
libido (sexual drive), hot flushes, occasional swelling of breast tissue and absent-mindedness. In
addition, if you receive the treatment over a long period of time you may notice an increase in
weight, a reduction in your muscle tissues and your bones may be weakened.
By taking a hormone therapy, which reduces body testosterone levels your bones may become
weakened, this effect is known as osteoporosis. In most cases, reduction in body testosterone
levels does not result in bone related side-effects. However, in a few severe cases it can be
associated with a significantly increased fracture risk.
a. Anti-hormone Injections: There are two types of anti-hormone injections known as LHRH
analogues and LHRH antagonists, these work in different ways but both result in stopping the
production of the male hormone testosterone by the testicles. Depending on the type of
injection, they are given around once every month or once every three months usually into the
skin of the abdomen or into the arm. Occasionally LHRH analogues temporarily aggravate the
cancer before a benefit occurs and for this reason additional tablets are given for the first few
weeks of the treatment. Other unwanted effects that have been reported are allergic reactions,
irritation at the injection site and headaches. The injections usually have to continue indefinitely.
OR
b. Anti-hormone tablet, such as bicalutamide: This tablet which is known as an anti-androgen
(AA), inhibits the uptake of testosterone by the prostate. A tablet will be taken once a day.
Unwanted side effects can include hot flushes, breast swelling, pain or tenderness and very
rarely mild liver toxicity.
What is prostate cryotherapy, and how does it work?
Prostate cryotherapy aims to eradicate prostate cancer by freezing prostate cells. Under
general anaesthesia, this is carried out by the surgeon inserting needles into the prostate gland
through the area between the scrotum and anus (the perineum). Very cold temperatures are
produced through channelling gas through the needles at high pressure. To have cryotherapy, a
number of metal probes are put through the skin and into the affected part of the prostate. The
probes contain liquid nitrogen or argon, which can freeze and destroy the cancer. Ultrasound is
used to guide the insertion of the needles and monitor the freezing process. The freezing
process may potentially destroy the entire prostate including cancerous tissue.
Prostate cryotherapy can be considered for patients who have relapsed prostate cancer following
previous radiotherapy for prostate cancer. A biopsy confirming recurrent prostate cancer is
required. Generally a scan of the pelvis and a bone scan are undertaken to determine that the
cancer is confined to within the prostate gland.
Possible side effects/ complications following prostate cryotherapy are outlined as below:
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1. Urinary problems (5-10%) - Cryotherapy can cause a variety of urinary problems.
Sometimes leakage of urine can occur following treatment. It is possible that this will
improve with time. Some men may need to use incontinence pads to protect their
underwear. All men are taught pelvic floor exercises to assist with their urinary control.
A small number of men have difficulty in passing urine after the treatment and require a
tube (catheter) to be passed to assist with this. This is usually left for around 2 weeks,
then removed. If this problem persists, occasionally an operation to “trim” or “stretch”
the prostate may be required to improve the urinary flow.
2. Erectile Dysfunction (impotence)(>80%) - As the nerves involved in creating an erection
lie just behind the prostate gland, they can be involved in the freezing process.
Treatment for erectile dysfunction is available on the NHS. Cryotherapy carries a higher
risk of erectile dysfunction than other treatments for prostate cancer. Often men have
problems with erectile dysfunction prior to cryotherapy, due to other treatments for
prostate cancer such as radiotherapy.
3. Rectal Problems – An uncommon complication (up to 5%) of cryotherapy is an abnormal
connection forming between the back passage (rectum) and the tube which carries the
urine (urethra). This is known as a fistula and is caused by the back passage being
affected during the cryotherapy treatment. Although rare, this complication is serious
and may require an operation to repair the hole. A “stoma”, where body fluids are
collected in an external bag worn on the body occasionally may be required.
Commonly asked questions (Q) and answers (A) for prostate cryotherapy:
Q
A
How long does cryotherapy take?
Approximately 2 hours under general anaesthetic.
Q
A
How long will I be in hospital?
2 nights, 1 night before the treatment and the night after treatment.
Q
A
Do I need any preparation for cryotherapy?
You require an ultrasound scan of your prostate to determine the size of the prostate
gland. This is carried out before treatment is arranged. The day before cryotherapy you
will be given 2 enemas to empty your back passage. This allows a clear ultrasound
picture to be obtained during the cryotherapy treatment.
Q
A
Will I experience pain after cryotherapy?
Most men describe discomfort rather than pain. We use paracetamol to control this,
however stronger pain killers will be used if required.
Q
A
Will I go home with a catheter (tube to drain the urine)?
Yes. The prostate swells following treatment therefore it would be difficult to pass urine.
The catheter remains in place for approximately 1 week, then you come back to the ward
for its removal. Nursing staff teach you how to look after the catheter before going
home.
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What are the side-effects?
(1) Hormone treatment
Cancer of the prostate depends on the male hormone testosterone for its growth. Hormone
therapy reduces the amount of testosterone in the body. The side-effects associated with the
reduction of testosterone levels in the body, either chemically (by injection) or by surgery, might
include; impotence, decreased sex drive (loss of libido), hot flushes, and occasionally may cause
a small amount of swelling of breast tissue. Long-term hormone therapy 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 and
there is no generally agreed way of dealing with this problem. This effect has not been observed
with hormone therapy based on restriction of the uptake of testosterone by the prostate.
(2) Prostate cryotherapy
Cryotherapy (also called cryosurgery) is a way of killing cancer cells by freezing them. To have
cryotherapy, a number of needle probes are put through the skin directly into the prostate. The
probes are connected to pressurised gases, which can freeze and destroy the cancer. Possible
side effects of prostate cryotherapy can develop early (within 1-2 weeks) and late (up to 2 to 3
months following treatment). Early side effects include discomfort in the perineum (the area
between the anus and the scrotum) after the procedure – this is usually self limiting and resolve
spontaneously at around 2 weeks. Late onset side effects can include slowing down of urinary
flow, urinary incontinence, impotence, damage to the rectum (leading to the formation of an
abnormal connection between the bladder and the rectum (bowel); this is called a fistula), and
the possibility of colostomy, an operation where your surgeon creates an opening of the bowel
onto your tummy, which may be temporary or permanent.
What are the possible advantages of taking part in the trial?
There are no objective data to allow you and your doctor to compare the effectiveness and the
related quality of life following either treatment options – that is why we are doing this study. It
might also remove the anxiety associated with making a choice between the available treatment
options (assuming you are prepared to accept either option for treatment). Within the study,
we propose to perform scans more regularly than usual. It may give a potential advantage of
identifying any potential problems early.
What are the possible disadvantages?
The treatment options and follow up are very similar to standard of care. We intend to carry out
additional scans every year to ensure that we have a very close monitor of the cancer status.
This should give additional information and apart from the commitment to attend the hospital
for tests, it can be an advantage to have additional information. There is some additional risk
associated with having these extra scans and this is explained in more detail below.
Do I have to take part?
It is up to you to decide whether or not to take part. If you do decide to take part, you will be
given this information sheet to keep and be asked to sign a consent form. If you do decide to
take part, you are still free to withdraw at any time and without giving reason and, your
subsequent treatment will not be affected in any way.
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To ensure full co-operation between the hospital and the surgery we will inform your GP about
the treatment and the details of the study.
What would happen to me if I took part?
If you join the study, you would follow one of the treatment options described above. If you are
randomised to receive cryotherapy followed by deferred Androgen Deprivation Therapy (Arm B)
you will be asked to visit the hospital for follow-up at 3 months after treatment, 6 months after
treatment and then once a year for up to 8 years. If you are randomised to receive deferred
Androgen Deprivation Therapy alone (Arm A) you will be contacted by a member of the study
team 3 months and 6 months after randomisation and you will be asked to attend a hospital
outpatient appointment annually for up to 8 years.
What will I have to do if I take part?
Prior to beginning the study, you will have some evaluations, which are considered routine
medical care and would be done whether or not you participate in this research study. These
include a physical exam, a PSA test and a bone scan.
In addition you will be asked to have an MRI scan before starting treatment and annually
thereafter for a maximum of 7 years. You will also be asked to have a bone scan annually for a
maximum of 7 years. You may have had a needle biopsy taken as part of the investigations to
show your cancer had returned following radiotherapy. If you have not had a biopsy, you will be
asked to have one now. The biopsy involves a very small needle being inserted into the tumour
to remove a small sample of tissue. There is a small risk of bleeding with this procedure, but it
is very rare for this to be serious enough to require treatment. These investigations provide us
additional information regarding the status of your cancer. You would not normally receive these
if you were not in the study. The MRI and bone scan will be done during routine hospital
appointments so you will not be asked to make additional visits.
There is little risk associated with an MRI. However, you may be uncomfortable or
claustrophobic while you are in the tunnel-shaped machine. You must not have metal objects
in or on your body during the scan as the powerful magnet used during the scan could exert a
damaging pull on them. Staff who are experienced in providing these investigations will be
present at all times.
During the bone scans you will be exposed to radioactive materials as these scans use
radioactive tracers to form images of the body. You will have more scans than is standard of
care if you were not participating in the study. The main risk of exposure to radioactive
materials/radiation is that another cancer may occur many years after the exposure. The
quantity of radiation received during the whole study would be equivalent to 12 years natural
background radiation exposure. This level is considered to be a moderate amount and would
involve a risk of death from such cancer induction of about 1 in 1500, but for a patient with
your condition, the additional risk of inducing such a cancer from this moderate exposure level
can be considered to be negligible.
If you decide to join the study you will also be asked to complete a questionnaire with about
50 questions. We will use these answers to learn how treatment affects your quality of life.
You will be asked to complete the questionnaire before starting your treatment, after 3
months, 6 months, 12 months and annually thereafter.
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If you receive prostate cryotherapy a small sample of cells (a biopsy) from your prostate will
be taken 6 months after you had your cryotherapy treatment. This is a normal procedure for
patients with your type of cancer after receiving cryotherapy and provides an additional means
to assess cancer response to the treatment. The procedure is identical to that used to initially
determine the recurrence of cancer following radiotherapy but typically we will do a fewer
number of needle biopsies (~6 in total). The risks include infection and transient bleeding from
the prostate. Biopsies negative for the presence of cancer, along with good PSA (blood test for
prostate cancer, will be consistent with favourable response to cryotherapy. However, if
biopsies were positive for residual or recurrent cancer, patient management will be guided
clinically and this information may influence the timing of additional treatment such as
androgen ablation.
What will happen to the results of the research study?
Our findings will be disseminated through conference presentations and journal articles and
through links already existing between the key funders of medical research including Cancer
Research UK, Medical Research Council and National Institute for Health Research, and various
hospital sites. Your study doctor will be informed of the results and he/she can discuss the
results with you and a copy of the results will be freely available to you on request. No patients
will be identified in such publications.
Will my taking part be kept confidential?
You can be assured that any data collected during the course of this study and any of the results
published will not identify you personally. Your medical records will only be available to the
research doctors, your hospital consultant, responsible individuals from the Cancer Research UK
Clinical Trials Unit (Glasgow), trial sponsors and regulatory authority. We will inform your
general practitioner of your participation in this study.
With your permission, the staff at the Cancer Research UK Clinical Trials Unit (Glasgow) who
are co-ordinating the study will collect your name or initials, date of birth and NHS number or
Community Health Index (CHI) number. This information will be stored securely and will be
kept strictly confidential, with access provided only to authorised personnel.
What if I change my mind about participating in the study?
If you change your mind about taking part in the study, you can withdraw from the study at any
time. This will not affect your relationship with the doctors and nurses, or your subsequent care,
in any way. Even though you would not be taking part in the study in this case, we would still
like to monitor your progress. If you agree we would like to continue to collect some information
so that the long-term effects of your treatment can be assessed.
Who is organising and funding this research?
The study is being co-ordinated by the Cancer Research UK Clinical Trials Unit, based at the
Beatson West of Scotland Cancer Centre, Glasgow. The study is being funded by a grant from
Cancer Research UK. The research doctors are not being paid for including you in this study.
What if something goes wrong?
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If you have any concerns about this study you should speak to your research doctor/nurse who
will do their best to answer your questions.
If you are harmed by taking part in this research project, there are no special compensation
arrangements. If you are harmed due to someone’s negligence, then you may have grounds for
legal action but you may have to pay your legal costs.
If you wish to complain, or have any concerns about any aspect of the way you have been
approached or treated during the course of this study, the normal National Health Service
complaints mechanisms will be available to you.
If you have private medical insurance, you may wish to check with your company before
agreeing to take part in the study to ensure that participation in the study will not affect your
insurance cover.
What if new information becomes available?
Sometimes during the course of a research project, new information becomes available about
the treatment that is being studied. If any new information becomes available that may affect
your participation in this study or would affect your future care, your study doctor will tell you
about it and discuss with you whether you want to continue in the study. If you decide to
withdraw, your study doctor will make arrangements for your care to continue. If you decide to
continue in the study you would be asked to sign an updated consent form.
What happens when the research study stops?
Irrespective of the research stopping, you will be followed up like any other patients under our
care who have prostate cancer.
Who has reviewed the study?
All research in the NHS is looked at by an independent group of people, called a Research
Ethics Committee to protect your interests. This study has been reviewed and given a
favourable opinion by the West of Scotland Research Ethics Committee 2, CRUK and NHS R&D
Greater Glasgow and Clyde.
Contact for further information
More information about clinical trials can be found on the Cancer Research UK's patient website,
Cancer Help UK (www.cancerhelp.org.uk, freephone: 0808 800 4040). Macmillan Cancer
Support also provide information on all aspects of cancer care including clinical trials (freephone
0800 808 00 00 or www. macmillan.org.uk).
You will now be given time to make your decision about whether to enter this study. If you
would like to discuss any aspect of this study with a doctor not directly involved, please contact
Cancer Help UK or Macmillan Cancer Support (contact details given above). The study doctor or
nurse can answer any questions you may have, and you can let them know if you are interested
in taking part. Thank you very much for considering taking part in our research. If you have
any questions regarding this research, or your participation, you should contact (during office
hours):
CROP: CRyOtherapy in Prostate cancer
Patient Information Sheet and consent form,
Version 3.1, 02 Feb 2012
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Doctor:
Name:
(insert local contact details)
Telephone Number:
or contact (insert local out of hours contact details) at all other times.
CROP: CRyOtherapy in Prostate cancer
Patient Information Sheet and consent form,
Version 3.1, 02 Feb 2012
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CONSENT FORM FOR PATIENTS IN A CLINICAL RESEARCH PROJECT
Title of Project:
A randomised controlled trial of deferred androgen deprivation therapy ± upfront cryotherapy in
men with localised radiation recurrent prostate cancer (RRPC) to evaluate efficacy and
tolerability.
(Acronym – CROP: CRyOtherapy in Prostate cancer)
Name of Researcher:
Patient Trial Number:
PLEASE
INITIAL
BOX
1
I confirm that I have read and understand the information sheet dated 2nd
February 2012 (Version 3.1) for the above study. I have had the
opportunity to consider the information, ask questions and have had these
answered satisfactorily.
2
I understand that my participation is voluntary and that I am free to
withdraw at any time, without giving any reason, without my medical care
or legal rights being affected.
3
I agree that relevant sections of any of my medical notes and data
collected during the study, may be looked at by responsible individuals
from the Cancer Research UK Clinical Trials Unit (Glasgow), the trial
sponsor and the regulatory authorities where it is relevant to my taking
part in research. I give permission for these individuals to have access to
my records.
4
I agree to my GP being informed of my participation in the study.
5
I agree to the information detailed in this patient information sheet to be
collected as part of this study
6
I agree to take part in the above study.
Please sign over the page:
CROP: CRyOtherapy in Prostate cancer
Patient Information Sheet and consent form,
Version 3.1, 02 Feb 2012
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CONSENT FORM FOR PATIENTS IN A CLINICAL RESEARCH PROJECT
Title of Project:
A randomised controlled trial of deferred androgen deprivation therapy ± upfront cryotherapy in
men with localised radiation recurrent prostate cancer (RRPC) to evaluate efficacy and
tolerability.
(Acronym – CROP: CRyOtherapy in Prostate cancer)
Name of Patient
Name
of
Person
taking
consent
Date
Signature
Date
Signature
When completed, 1 for patient, 1 for researcher, 1 to be kept with hospital notes
CROP: CRyOtherapy in Prostate cancer
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Version 3.1, 02 Feb 2012
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